Maternal obesity and ovarian failure: is leptin the culprit?

At the time of its discovery and characterization in 1994, leptin was mostly considered a metabolic hormone able to regulate body weight and energy homeostasis. However, in recent years, a great deal of literature has revealed leptin's pleiotropic nature, through its involvement in numerous physiological contexts including the regulation of the female reproductive tract and ovarian function. Obesity has been largely associated with infertility, and leptin signalling is known to be dysregulated in the ovaries of obese females. Hence, the disruption of ovarian leptin signalling was shown to contribute to the pathophysiology of ovarian failure in obese females, affecting transcriptional programmes in the gamete and somatic cells. This review attempts to uncover the underlying mechanisms contributing to female infertility associated with obesity, as well as to shed light on the role of leptin in the metabolic dysregulation within the follicle, the effects on the oocyte epigenome, and the potential long-term consequence to embryo programming.(AU)

Markers of inflammation and insulin resistance in dogs before and after weight loss versus lean healthy dogs / Marcadores de inflamação e resistência à insulina em cães antes e depois da perda de peso versus cães saudáveis e magros

Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory cytokines that contribute to insulin resistance. For this study body composition, markers of inflammation and of insulin resistance in dogs before and after weight loss were compared to those of lean dogs. Eleven client-owned obese adult dogs underwent a weight loss program with commercial dry food for weight loss and reached an ideal body condition score (BCS) six months after the beginning of the weight loss program. A Control Group of nine dogs with ideal BCS were selected for the comparison. Shapiro-Wilk test was used to test for normality, Mann Whitney were used for non-normally distributes data, and Student t-test was used for normally distributed parameters. In the Obese Group body fat decreased from 41.6% (30.7-58.6) to 29.1% (18.6-46.3) (P<0.01) and dogs maintained lean body mass throughout the weight loss program (P>0.05). Obese dogs presented higher concentration of fructosamine, triglycerides, insulin, IGF-1 and leptin than the Control Group before weight reduction (P<0.05). Serum concentrations of triglycerides, IL-2, IL-6, TNF-α, insulin, leptin and IGF-1 decreased after weight loss (P<0.01), and these concentrations were similar to the Control Group (P>0.05), except for leptin (P<0.001). No alteration on peptide YY was found. Leptin (r=0.60, P=0.01), fructosamine (r=0.44, P=0.02) and triglycerides (r=0.40, P=0.04) concentrations correlated with the reduction of body fat. Weight loss reduced the concentrations of inflammatory and insulin resistance markers and most parameters became similar to dogs that have always been lean, reinforcing the importance of weight loss in small animal practice.(AU)

A inflamação crônica de baixo grau na obesidade é caracterizada pela produção aumentada de citocinas pró-inflamatórias que contribuem para a resistência à insulina. Para este estudo a composição corporal e os marcadores de inflamação e de resistência à insulina em cães antes e após a perda de peso foram comparados aos de cães magros. Onze cães adultos obesos pertencentes a tutores foram incluídos em um programa de perda de peso com ração comercial hipocalórica e alcançaram escore de condição corporal (ECC) ideal seis meses após o início do regime. Um Grupo Controle de nove cães com ECC ideal foi selecionado para a comparação. O teste de Shapiro-Wilk foi usado para testar a normalidade, Mann Whitney foi usado para análise dos dados que não atenderam distribuição normal e o teste t de Student foi usado para parâmetros que atenderam a normalidade. No Grupo Obesidade, a gordura corporal diminuiu de 41,6% (30,7-58,6) para 29,1% (18,6-46,3) (P<0,01) e os cães mantiveram massa magra ao longo do programa de perda de peso (P>0,05). Cães obesos apresentaram maior concentração de frutosamina, triglicérides, insulina, IGF-1 e leptina do que o Grupo Controle antes da redução de peso (P<0,05). As concentrações séricas de triglicerídeos, IL-2, IL-6, TNF-α, insulina, leptina e IGF-1 diminuíram após a perda de peso (P<0,01) e, essas concentrações foram semelhantes ao Grupo Controle (P>0,05), com exceção da leptina (P<0,001). Nenhuma alteração no peptídeo YY foi encontrada. As concentrações de leptina (r=0,60; P=0,01), frutosamina (r=0,44; P=0,02) e triglicerídeos (r=0,40; P=0,04) correlacionaram-se com a redução da gordura corporal. A perda de peso reduziu as concentrações de marcadores inflamatórios e de resistência à insulina e a maioria dos parâmetros tornaram-se semelhante aos dos cães que sempre foram magros, reforçando a importância da perda de peso na prática clínica de pequenos animais.(AU)

Markers of inflammation and insulin resistance in dogs before and after weight loss versus lean healthy dogs / Marcadores de inflamação e resistência à insulina em cães antes e depois da perda de peso versus cães saudáveis e magros

Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory cytokines that contribute to insulin resistance. For this study body composition, markers of inflammation and of insulin resistance in dogs before and after weight loss were compared to those of lean dogs. Eleven client-owned obese adult dogs underwent a weight loss program with commercial dry food for weight loss and reached an ideal body condition score (BCS) six months after the beginning of the weight loss program. A Control Group of nine dogs with ideal BCS were selected for the comparison. Shapiro-Wilk test was used to test for normality, Mann Whitney were used for non-normally distributes data, and Student t-test was used for normally distributed parameters. In the Obese Group body fat decreased from 41.6% (30.7-58.6) to 29.1% (18.6-46.3) (P<0.01) and dogs maintained lean body mass throughout the weight loss program (P>0.05). Obese dogs presented higher concentration of fructosamine, triglycerides, insulin, IGF-1 and leptin than the Control Group before weight reduction (P<0.05). Serum concentrations of triglycerides, IL-2, IL-6, TNF-α, insulin, leptin and IGF-1 decreased after weight loss (P<0.01), and these concentrations were similar to the Control Group (P>0.05), except for leptin (P<0.001). No alteration on peptide YY was found. Leptin (r=0.60, P=0.01), fructosamine (r=0.44, P=0.02) and triglycerides (r=0.40, P=0.04) concentrations correlated with the reduction of body fat. Weight loss reduced the concentrations of inflammatory and insulin resistance markers and most parameters became similar to dogs that have always been lean, reinforcing the importance of weight loss in small animal practice.(AU)

A inflamação crônica de baixo grau na obesidade é caracterizada pela produção aumentada de citocinas pró-inflamatórias que contribuem para a resistência à insulina. Para este estudo a composição corporal e os marcadores de inflamação e de resistência à insulina em cães antes e após a perda de peso foram comparados aos de cães magros. Onze cães adultos obesos pertencentes a tutores foram incluídos em um programa de perda de peso com ração comercial hipocalórica e alcançaram escore de condição corporal (ECC) ideal seis meses após o início do regime. Um Grupo Controle de nove cães com ECC ideal foi selecionado para a comparação. O teste de Shapiro-Wilk foi usado para testar a normalidade, Mann Whitney foi usado para análise dos dados que não atenderam distribuição normal e o teste t de Student foi usado para parâmetros que atenderam a normalidade. No Grupo Obesidade, a gordura corporal diminuiu de 41,6% (30,7-58,6) para 29,1% (18,6-46,3) (P<0,01) e os cães mantiveram massa magra ao longo do programa de perda de peso (P>0,05). Cães obesos apresentaram maior concentração de frutosamina, triglicérides, insulina, IGF-1 e leptina do que o Grupo Controle antes da redução de peso (P<0,05). As concentrações séricas de triglicerídeos, IL-2, IL-6, TNF-α, insulina, leptina e IGF-1 diminuíram após a perda de peso (P<0,01) e, essas concentrações foram semelhantes ao Grupo Controle (P>0,05), com exceção da leptina (P<0,001). Nenhuma alteração no peptídeo YY foi encontrada. As concentrações de leptina (r=0,60; P=0,01), frutosamina (r=0,44; P=0,02) e triglicerídeos (r=0,40; P=0,04) correlacionaram-se com a redução da gordura corporal. A perda de peso reduziu as concentrações de marcadores inflamatórios e de resistência à insulina e a maioria dos parâmetros tornaram-se semelhante aos dos cães que sempre foram magros, reforçando a importância da perda de peso na prática clínica de pequenos animais.(AU)

Neuroendocrine signaling pathways and the nutritional control of puberty in heifers

Puberty is a complex physiological process in females that requires maturation of the reproductive neuroendocrine system and subsequent initiation of highfrequency, episodic release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Genetics and nutrition are two major factors controlling the timing of puberty in heifers. While nutrient restriction during the juvenile period delays puberty, accelerated rates of body weight gain during this period have been shown to facilitate pubertal development by programming hypothalamic centers that underlie the pubertal process. Among the different metabolic factors, leptin plays a critical role in conveying nutritional information to the neuroendocrine axis and controlling pubertal progression. Because GnRH neurons are devoid of the leptin receptor, leptin’s effects on GnRH neurons must be relayed via an afferent neuronal network. Two neuronal populations located in the arcuate nucleus (ARC) that express the orexigenic peptide neuropeptide Y (NPY), and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH), are key components of afferent pathways that convey inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. In addition, ARC neurons expressing kisspeptin, a potent stimulator of GnRH release, are also involved in the nutritional regulation of puberty. Our studies have demonstrated that increased planes of nutrition during juvenile development result in morphological and functional changes in hypothalamic pathways comprising NPY, proopiomelanocortin (POMC), and kisspeptin neurons. Changes included differential expression of NPY, POMC, and Kiss1 in the ARC, and plasticity in the axonal projections to GnRH and kisspeptin neurons. Additionally, increased rates of body weight gain also promoted changes in the pattern of DNA methylation, a key epigenetic mechanism for regulation of gene expression. Finally, our most recent findings suggest that maternal nutrition during gestation can also induce structural and functional changes in hypothalamic neurocircuitries that are likely to persist long after pubertal maturation and influence reproductive performance throughout adulthood in cattle.

Neuroendocrine signaling pathways and the nutritional control of puberty in heifers

Puberty is a complex physiological process in females that requires maturation of the reproductive neuroendocrine system and subsequent initiation of highfrequency, episodic release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Genetics and nutrition are two major factors controlling the timing of puberty in heifers. While nutrient restriction during the juvenile period delays puberty, accelerated rates of body weight gain during this period have been shown to facilitate pubertal development by programming hypothalamic centers that underlie the pubertal process. Among the different metabolic factors, leptin plays a critical role in conveying nutritional information to the neuroendocrine axis and controlling pubertal progression. Because GnRH neurons are devoid of the leptin receptor, leptins effects on GnRH neurons must be relayed via an afferent neuronal network. Two neuronal populations located in the arcuate nucleus (ARC) that express the orexigenic peptide neuropeptide Y (NPY), and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH), are key components of afferent pathways that convey inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. In addition, ARC neurons expressing kisspeptin, a potent stimulator of GnRH release, are also involved in the nutritional regulation of puberty. Our studies have demonstrated that increased planes of nutrition during juvenile development result in morphological and functional changes in hypothalamic pathways comprising NPY, proopiomelanocortin (POMC), and kisspeptin neurons. Changes included differential expression of NPY, POMC, and Kiss1 in the ARC, and plasticity in the axonal projections to GnRH and kisspeptin neurons. Additionally, increased rates of body weight gain also promoted changes in the pattern of DNA methylation, a key epigenetic mechanism for regulation of gene expression. Finally, our most recent findings suggest that maternal nutrition during gestation can also induce structural and functional changes in hypothalamic neurocircuitries that are likely to persist long after pubertal maturation and influence reproductive performance throughout adulthood in cattle.(AU)

Productive and reproductive parameters in high and low growing Syrian Awassi lambs / Parâmetros produtivos e reprodutivos de cordeiros Awassi da Síria de taxa rápida e lenta de crescimento

The objective of this study was characterize some productive and reproductive parametersin Syrian Awassi ewe lambs during different age stages. Thirty Syrian Awassi ewe lambs aged around 3months were divided equally into 2 groups, high and low growing to identify productive and reproductiveparameters during different stages. Blood samples were collected to determine progesterone and leptinconcentrations. Daily milk samples were collected to determine the average daily production. At puberty,average body weight of higher growing was higher (48.4 kg) than de crescimento low growing (42.8 kg).Average age at puberty was 359.5 and 394.9 days for high and low groups, respectively with no differences.Mating, lambing and fecundity rates were similar among groups. Progesterone concentration was very low and increased rapidly at puberty with a sharp increase during pregnancy, followed by a noticeable decreasepost lambing. There were individual variations in leptin concentration with no clear trend in groups. Average leptin concentration at puberty was 2.42 and 2.50 ng mL-1 for higher and low groups, respectivelywith no difference. Average daily milk production was higher for the higher group (1.495 g day-1) compared to 1.077 g day-1 for low grups. Thus, the lambs growing alter produtive and reproductive parameters.(AU)

O objetivo deste estudo foi caracterizar alguns parâmetros produtivos e reprodutivos emcordeiros sírios Awassi com diferentes estpagio de crescimento. Trinta cordeiros Awassi com cerca de 3meses de idade foram divididos igualmente em dois grupos: cordeiros de crescimento rápido e lento, paraidentificar os parâmetros produtivo e reprodutivo, durante diferentes estágios. Foram coletadas amostras desangue para determinar a concentração de progesterona e leptina. Também, foram coletadas amostrasdiárias de leite para determinar a média de produção diária. Na puberdade, a média geral dos pesos doscordeiros de crescimento rápido foi maior (48,4 kg) comparado aos de crescimento lento (42,8 kg). A idademédia da puberdade foi de 359,5 e 394,9 dias para o grupo rápido e lento, sem diferenças. As taxas deacasalamento, parto e fecundidade foram semelhantes entres os grupos. A concentração de progesterona foibaixa e aumentou rápidamente na puberdade, com um aumento acentuado durante a gravidez, seguido porum notável decrescimento no pós-parto. Houve variações individuais na concentração de leptina sem umaclara tendência nos grupos. A média de concentração de leptina na puberdade foi de 2,42 e 2,50 ng mL-1para o grupo de higher and low, respectivamente. A produção diária de leite foi maior para o grupo decrescimento rápido (1.495 g dia-1) comparada com 1.077g dia-1 para os animais de crescimento fraco. Assim,a taxa de crescimento alterou os parâmetros produtivos e reprodutivos.(AU)

Productive and reproductive parameters in high and low growing Syrian Awassi lambs / Parâmetros produtivos e reprodutivos de cordeiros Awassi da Síria de taxa rápida e lenta de crescimento

The objective of this study was characterize some productive and reproductive parametersin Syrian Awassi ewe lambs during different age stages. Thirty Syrian Awassi ewe lambs aged around 3months were divided equally into 2 groups, high and low growing to identify productive and reproductiveparameters during different stages. Blood samples were collected to determine progesterone and leptinconcentrations. Daily milk samples were collected to determine the average daily production. At puberty,average body weight of higher growing was higher (48.4 kg) than de crescimento low growing (42.8 kg).Average age at puberty was 359.5 and 394.9 days for high and low groups, respectively with no differences.Mating, lambing and fecundity rates were similar among groups. Progesterone concentration was very low and increased rapidly at puberty with a sharp increase during pregnancy, followed by a noticeable decreasepost lambing. There were individual variations in leptin concentration with no clear trend in groups. Average leptin concentration at puberty was 2.42 and 2.50 ng mL-1 for higher and low groups, respectivelywith no difference. Average daily milk production was higher for the higher group (1.495 g day-1) compared to 1.077 g day-1 for low grups. Thus, the lambs growing alter produtive and reproductive parameters.

O objetivo deste estudo foi caracterizar alguns parâmetros produtivos e reprodutivos emcordeiros sírios Awassi com diferentes estpagio de crescimento. Trinta cordeiros Awassi com cerca de 3meses de idade foram divididos igualmente em dois grupos: cordeiros de crescimento rápido e lento, paraidentificar os parâmetros produtivo e reprodutivo, durante diferentes estágios. Foram coletadas amostras desangue para determinar a concentração de progesterona e leptina. Também, foram coletadas amostrasdiárias de leite para determinar a média de produção diária. Na puberdade, a média geral dos pesos doscordeiros de crescimento rápido foi maior (48,4 kg) comparado aos de crescimento lento (42,8 kg). A idademédia da puberdade foi de 359,5 e 394,9 dias para o grupo rápido e lento, sem diferenças. As taxas deacasalamento, parto e fecundidade foram semelhantes entres os grupos. A concentração de progesterona foibaixa e aumentou rápidamente na puberdade, com um aumento acentuado durante a gravidez, seguido porum notável decrescimento no pós-parto. Houve variações individuais na concentração de leptina sem umaclara tendência nos grupos. A média de concentração de leptina na puberdade foi de 2,42 e 2,50 ng mL-1para o grupo de higher and low, respectivamente. A produção diária de leite foi maior para o grupo decrescimento rápido (1.495 g dia-1) comparada com 1.077g dia-1 para os animais de crescimento fraco. Assim,a taxa de crescimento alterou os parâmetros produtivos e reprodutivos.

Comparação do índice de massa corporal felino com a concentração plasmática de leptina e escore de condição corporal para o diagnóstico de obesidade em gatos domésticos / Comparison among feline’s body mass index, leptin hormone serum level and body condition score to diagnose obesity in domestic cats

Background: Today, obesity is a condition commonly seen in small animal internal medicine. This condition is defined as excess of body fat resulting from increased energy absorption or reduced energy expenditure, and it is classified as a nutritional and metabolic disorder. Obesity results from excessive formation of adipose tissue, and can pose severe consequences to the animal’s health. It can also become an aggravating factor for several diseases, frequently exerting direct effects on morbidity and mortality. This study aimed to evaluate feline body mass index (FBMI), and associate this parameter with body condition score (BCS) and leptin hormone serum levels.Materials, Methods & Results: This study was conducted in a private Veterinary Clinic exclusively dedicated to feline care in the neighborhood of Botafogo, city of Rio de Janeiro, Brazil. Ninety-six feline patients (Felis catus) were randomly selected independent of their gender (male or female - intact or not), breed, or age from cats that were submitted for surgical interventions. The population was then divided into two groups according to FBMI: group 1, with non-obese animals (FBMI < 30%), totaling 53 animals; and group 2, with obese animals (FBMI ≥ 30%), totaling 43 animals. Physical examination was conducted on all animals. During this procedure, the weight of the animals was recorded; obesity was determined subjectively using the BCS, and objectively using plasma leptin concentration as assessed by radioimmunoassay (RIA). Leptin concentration in the plasma of the 96 animals included in this study was 13.81 ± 13.06 ng/mL HE. The average for group 1 was 3.85 ± 3.08 ng/mL HE, while the average for group 2 was 26.08 ± 9.61 ng/mL HE.[...]

Comparação do índice de massa corporal felino com a concentração plasmática de leptina e escore de condição corporal para o diagnóstico de obesidade em gatos domésticos / Comparison among felines body mass index, leptin hormone serum level and body condition score to diagnose obesity in domestic cats

Background: Today, obesity is a condition commonly seen in small animal internal medicine. This condition is defined as excess of body fat resulting from increased energy absorption or reduced energy expenditure, and it is classified as a nutritional and metabolic disorder. Obesity results from excessive formation of adipose tissue, and can pose severe consequences to the animals health. It can also become an aggravating factor for several diseases, frequently exerting direct effects on morbidity and mortality. This study aimed to evaluate feline body mass index (FBMI), and associate this parameter with body condition score (BCS) and leptin hormone serum levels.Materials, Methods & Results: This study was conducted in a private Veterinary Clinic exclusively dedicated to feline care in the neighborhood of Botafogo, city of Rio de Janeiro, Brazil. Ninety-six feline patients (Felis catus) were randomly selected independent of their gender (male or female - intact or not), breed, or age from cats that were submitted for surgical interventions. The population was then divided into two groups according to FBMI: group 1, with non-obese animals (FBMI < 30%), totaling 53 animals; and group 2, with obese animals (FBMI ≥ 30%), totaling 43 animals. Physical examination was conducted on all animals. During this procedure, the weight of the animals was recorded; obesity was determined subjectively using the BCS, and objectively using plasma leptin concentration as assessed by radioimmunoassay (RIA). Leptin concentration in the plasma of the 96 animals included in this study was 13.81 ± 13.06 ng/mL HE. The average for group 1 was 3.85 ± 3.08 ng/mL HE, while the average for group 2 was 26.08 ± 9.61 ng/mL HE.[...](AU)

Imunolocalização de receptores de leptina no ovário de preás (Galea spixii Wagler, 1831) / Immunolocalization of leptin receptor of Spix's Yellow-toothed Cavy (Galea spixii Wagler, 1831) ovary

A leptina, uma citocina produzida pelas células adiposas, é alvo da comunidade científica por acreditarem que ela apresente impacto sobre a reprodução dos animais promovendo a puberdade, foliculogênese e oogênese, ciclo estral e auxiliando na fecundação. A compreensão dos mecanismos que controlam a atividade reprodutiva de preás (Galea spixii) possui papel relevante para a preservação da espécie. Desta forma, o presente trabalho propôs analisar a imunolocalização dos receptores de leptina (Ob-R) no ovário de preás. Coletaram-se os ovários de 20 fêmeas adultas, não prenhes e saudáveis. As amostras foram fixadas em paraformaldeído a 4% em tampão fosfato, incluídas em parafina e seccionadas para a realização de imunohistoquímica (IHC). As secções foram fotomicrografadas e avaliadas quanto à intensidade da reação. Observou-se forte imunorreação no oócito e nas células da teca, moderada nas células do estroma ovariano e nas células luteínicas grandes e fracamente coradas nas células da granulosa, endoteliais, perivasculares e células luteínicas pequenas. Quando comparado a expressão de receptores ao longo do desenvolvimento folicular foi observado que o oócito e as células da teca se mantiveram com expressão na mesma intensidade. Entretanto, as células da granulosa apresentaram forte marcação nos estádios pré-antrais enquanto que nos folículos antrais apresentou fraca intensidade. Concluímos que em ovários de Galea spixii existe a presença de Ob-R nas principais estruturas do ovário sugerindo que este hormônio desempenhe papel fundamental na reprodução desta espécie.(AU)

Leptin, a cytokine produced by adipose cells, is the target of the scientific community for believing that it has an impact on the reproduction of the animals promoting puberty, folliculogenesis and oogenesis, estrous cycle and aiding in fertilization. The understanding of the mechanisms controlling the reproductive activity of Spix's Yellow-toothed Cavy (Galea spixii) plays a relevant role in the preservation of the species. Thus, the present study proposed to analyze the immunolocalization of leptin receptors (Ob-R) in the ovary of cavies. Ovaries from 20 adult, non-pregnant, healthy females were collected. The samples were fixed in 4% phosphate buffered paraformaldehyde, embedded in paraffin and sectioned for immunohistochemistry. The sections were photomicrographs and intensity of the reaction was measured. Strong immunoreaction was observed in oocyte and theca cells, moderate in ovarian stromal cells and large luteal cells and weak stained in granulosa, endothelial, perivascular and small luteal cells. When compared to receptor expression along follicular development it was observed that the oocyte and the theca cells remained with expression at the same intensity. However, the granulosa cells presented strong stained in the preantral stages, whereas in the antral follicles it presented low intensity. We conclude that in the ovaries of Galea spixii there is the presence of Ob-R in the main structures of the ovary sugesting that this hormone plays a fundamental role in the reproduction of this species.(AU)

Imunolocalização de receptores de leptina no ovário de preás (Galea spixii Wagler, 1831) / Immunolocalization of leptin receptor of Spix's Yellow-toothed Cavy (Galea spixii Wagler, 1831) ovary

A leptina, uma citocina produzida pelas células adiposas, é alvo da comunidade científica por acreditarem que ela apresente impacto sobre a reprodução dos animais promovendo a puberdade, foliculogênese e oogênese, ciclo estral e auxiliando na fecundação. A compreensão dos mecanismos que controlam a atividade reprodutiva de preás (Galea spixii) possui papel relevante para a preservação da espécie. Desta forma, o presente trabalho propôs analisar a imunolocalização dos receptores de leptina (Ob-R) no ovário de preás. Coletaram-se os ovários de 20 fêmeas adultas, não prenhes e saudáveis. As amostras foram fixadas em paraformaldeído a 4% em tampão fosfato, incluídas em parafina e seccionadas para a realização de imunohistoquímica (IHC). As secções foram fotomicrografadas e avaliadas quanto à intensidade da reação. Observou-se forte imunorreação no oócito e nas células da teca, moderada nas células do estroma ovariano e nas células luteínicas grandes e fracamente coradas nas células da granulosa, endoteliais, perivasculares e células luteínicas pequenas. Quando comparado a expressão de receptores ao longo do desenvolvimento folicular foi observado que o oócito e as células da teca se mantiveram com expressão na mesma intensidade. Entretanto, as células da granulosa apresentaram forte marcação nos estádios pré-antrais enquanto que nos folículos antrais apresentou fraca intensidade. Concluímos que em ovários de Galea spixii existe a presença de Ob-R nas principais estruturas do ovário sugerindo que este hormônio desempenhe papel fundamental na reprodução desta espécie.

Leptin, a cytokine produced by adipose cells, is the target of the scientific community for believing that it has an impact on the reproduction of the animals promoting puberty, folliculogenesis and oogenesis, estrous cycle and aiding in fertilization. The understanding of the mechanisms controlling the reproductive activity of Spix's Yellow-toothed Cavy (Galea spixii) plays a relevant role in the preservation of the species. Thus, the present study proposed to analyze the immunolocalization of leptin receptors (Ob-R) in the ovary of cavies. Ovaries from 20 adult, non-pregnant, healthy females were collected. The samples were fixed in 4% phosphate buffered paraformaldehyde, embedded in paraffin and sectioned for immunohistochemistry. The sections were photomicrographs and intensity of the reaction was measured. Strong immunoreaction was observed in oocyte and theca cells, moderate in ovarian stromal cells and large luteal cells and weak stained in granulosa, endothelial, perivascular and small luteal cells. When compared to receptor expression along follicular development it was observed that the oocyte and the theca cells remained with expression at the same intensity. However, the granulosa cells presented strong stained in the preantral stages, whereas in the antral follicles it presented low intensity. We conclude that in the ovaries of Galea spixii there is the presence of Ob-R in the main structures of the ovary sugesting that this hormone plays a fundamental role in the reproduction of this species.

Leptin and IGF-I improve bovine embryo quality in vitro

The in vitro embryo culture systems need further improvement to enhance the efficiency of bovine embryo production. Growth factors play key roles in embryo production and quality. The objective of this study was to define the effects of leptin, insulin-like growth factor-1 (IGF-1), and their combination on embryonic development, apoptosis, and expression profiles of a panel of developmentally important genes during 8-day embryo culture. The oocytes were aspirated from slaughterhouse ovaries of mixed breed cows. Following IVM/IVF presumptive zygotes were obtained. To accomplish this objective, presumptive zygotes (16-18 h post-insemination) were cultured in vitro as control (no supplementation, n = 349), 5 ng/ml leptin (Group I, n = 322), 100 ng/ml IGF-1 (Group II, n = 347), and 5 ng/ml leptin and 100 ng/ml IGF-1 (Group III, n = 360). All groups were supplemented with 10% fetal calf serum (FCS) on Day 4, and blastocysts were harvested on day 8. The DNA fragmented nuclei of blastocyst were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and expression profiles of a panel of developmentally important genes were assayed by real-time polymerase chain reaction (RT-PCR). The cleavage rate and embryo development to 8-16 cell stage were higher in groups II and III as compared to control (P < 0.05), respectively. Percentage of blastocyst and mean cell numbers per blastocyst did not differ among the groups. Addition of IGF-I and/or combination with leptin decreased the number of nuclei with fragmented DNA (P < 0.01) as compared to the control group. Although the expression of glucose transporter 1 (Glut1), desmosomal glycoprotein desmocollin III (DcIII) and insulin like growth factor 2receptor (Igf2r) transcripts did not change among thegroups, interferon-tau (IF-tau) and DNAmethyltransferase 3A (Dnmt3a) were down-regulated ingroup II while heat shock protein-70 (Hsp70) and IF-tauwere up regulated in group III.[...]

Leptin and IGF-I improve bovine embryo quality in vitro

The in vitro embryo culture systems need further improvement to enhance the efficiency of bovine embryo production. Growth factors play key roles in embryo production and quality. The objective of this study was to define the effects of leptin, insulin-like growth factor-1 (IGF-1), and their combination on embryonic development, apoptosis, and expression profiles of a panel of developmentally important genes during 8-day embryo culture. The oocytes were aspirated from slaughterhouse ovaries of mixed breed cows. Following IVM/IVF presumptive zygotes were obtained. To accomplish this objective, presumptive zygotes (16-18 h post-insemination) were cultured in vitro as control (no supplementation, n = 349), 5 ng/ml leptin (Group I, n = 322), 100 ng/ml IGF-1 (Group II, n = 347), and 5 ng/ml leptin and 100 ng/ml IGF-1 (Group III, n = 360). All groups were supplemented with 10% fetal calf serum (FCS) on Day 4, and blastocysts were harvested on day 8. The DNA fragmented nuclei of blastocyst were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and expression profiles of a panel of developmentally important genes were assayed by real-time polymerase chain reaction (RT-PCR). The cleavage rate and embryo development to 8-16 cell stage were higher in groups II and III as compared to control (P < 0.05), respectively. Percentage of blastocyst and mean cell numbers per blastocyst did not differ among the groups. Addition of IGF-I and/or combination with leptin decreased the number of nuclei with fragmented DNA (P < 0.01) as compared to the control group. Although the expression of glucose transporter 1 (Glut1), desmosomal glycoprotein desmocollin III (DcIII) and insulin like growth factor 2receptor (Igf2r) transcripts did not change among thegroups, interferon-tau (IF-tau) and DNAmethyltransferase 3A (Dnmt3a) were down-regulated ingroup II while heat shock protein-70 (Hsp70) and IF-tauwere up regulated in group III.[...](AU)

SUPLEMENTAÇÃO MINERAL INJETÁVEL, EFEITO NA IATF E TE EM BOVINOS DE CORTE

A bovinocultura de corte é uma atividade ocorrente em todas as regiões do país e de extrema relevância na participação do PIB nacional, sendo considerada uma das principais atividades econômicas desenvolvidas. No que se refere ao efetivo do rebanho de bovinos de corte no Brasil, a maior parte é representada por raças zebuínas, constituindo cerca de 80%, destacando-se a Nelore, que compõe aproximadamente 75%. O trabalho foi realizado na propriedade Fazenda Alta Floresta, nas coordenadas 451 9°1134.51S 68°4736.67. O início do experimento em Maio de 2020 e encerramento Dezembro de 2020, totalizando 7 meses de coletas, avaliações e compilação de dados. Todos os animais utilizados neste experimento possuíam mais de 36 meses, da raça Nelore e com descedência de touros da raça Nelore tem Edhupati do Arroio, Ebhumady do Arroio, Jeru FIV da Brumado. Buscou-se Avaliar a taxa de prenhez em fêmeas bovinas, observando a correlação da taxa de prenhez em fêmeas bovinas com ECC diferentes e efeito da suplementação injetável na taxa de prenhez em diferentes ECC na IATF. Apesar de amostragem expressiva para a condução deste experimento, a utilização desuplementação mineral injetável como medida apropriada para o aumento da condição de escore corporal a curto prazo, somente apresentou diferenças quando condições corporais de desafio, contudo, essa tendência de aumento da taxa de prenhez de animais em desafio não se confirmou quando comparado as taxas de prenhez em receptoras e não demonstrou diferença nos demais grupos. O status das exigências minerais atendidas podem refletir diretamente no aumento produtivo e desempenho reprodutivo dos animais submetidos a este manejo, nas quais agrega valor aos produtos (bezerros) produzidos a partir do uso das técnicas para intensificação da pecuária como suplementação injetável e IATF.

Beef cattle is an activity that is an activity that is common in all regions of the country and is extremely relevant in the participation of national GDP, being considered one of the main economic activities developed. Regarding the herd of beef cattle in Brazil, most of them are represented by zebu breeds, constituting about 80%, especially Nellore, which makes up approximately 75%. The work was carried out at the Farm Alta Floresta property, at coordinates 451 9°11'34.51''S 68°47'36.67''. The beginning of the experiment in May 2020 and closing December 2020, totaling 7 months of data collection, evaluation and compilation. All the animals used in this experiment were more than 36 months old, nellore breed and with descent of nellore bulls has Edhupati do Arroio, Ebhumady do Arroio, Jeru FiV of Brumado. We sought to evaluate the pregnancy rate in bovine females, observing the correlation of pregnancy rate in bovine females with different CCS and effect of injectable supplementation on pregnancy rate in different CCS in IATF. Despite significant sampling for the conduction of this experiment, the use of injectable mineral supplementation as an appropriate measure for increasing the condition of body score in the short term only showed differences when body conditions of challenge, however, this tendency to increase the pregnancy rate of animals in challenge was not confirmed when compared to pregnancy rates in recipients and showed no difference in the other groups. The status of the mineral requirements met may directly reflect the increase in reproductive performance of animals submitted to this management, in which it aggregates value to products (calves) produced from the use of techniques for cattle intensification such as injectable supplementation and IATF.

EFEITO DE MEDICAMENTOS ULTRADILUIDOS NA OBESIDADE CANINA

A obesidade, uma doença multifatorial temcomodefiniçãooacúmulo excessivode tecido adiposo no corpo, sendo a desordem nutricionalmaiscomum em cães e gatos,em decorrência, em sua grande maioria,daingestaalimentarexcessiva ou utilização inadequada de energia. Inúmeros estudos indicam quea incidênciade sobrepeso/obesidade na população canina está em constante crescente, assim como suas implicações.Oobjetivo dopresente estudo foi avaliaros efeitos da administração de medicamentos ultradiluídos e dinamizadosem cães com obesidade. Foram avaliados38cãescomprovadamente obesos, de ambos os sexos, em sua grande maioria sem raça definida, entre 2até 13anos de idade, todos gonadectomizados. Foram avaliadoso peso, escore de condição corporal (ECC), porcentagem de gordura corporal (%GC), índice de massa corporal canina (IMCC), bem como circunferência abdominal e torácica e a espessura do tecido adiposo em região de sétima vertebra lombarpor exame ultrassonográfico. Essas avaliações ocorreramem dois temposcom umintervalode 60 diasentre o início e fim do estudo,os animais foramdivididosaleatoriamenteem três grupos, 10 animaispertencentes ao grupo controle (GC), 15 animais pertencentes ao grupo droga A(GDA) e 13animais pertencentes ao grupo droga B(GDB).Os animais do GC não receberam medicamentos, enquanto os animais dos demais grupos receberam 5 gotaspor via oral duas vezes ao dia dosrespectivos grupos medicamentosos durante60 dias. Os medicamentos e suas respectivas dinamizações foram divididos em dois grupos e nomeados como remédio A (Fucus vesiculosos 6cH+ Calcarea carbônica 12cH)e remédio B(Hyphotalamus 6cH+ Leptina 8cH+ Thyroidinum 5cH). Os resultados obtidos nesse estudo corroboram com outras pesquisas com relação ao perfildo cão obeso, onde sua maior incidênciaestá em cães de meia idade ou idosos, animais gonadectomizados, com dietas hipercalóricas e poucaatividade física,além de demonstrarque os animais tratados com os medicamentos Calcarea carbônicae Fucus vesiculosos, apresentaram reduçãona porcentagem de gordura e circunferência abdominal(p 0.05), e os medicamentos Hyphotalamus 6 cH+ Leptina 8 cH+ Thyroidinum 5 cHapresentaram redução no escore corporal(p 0.05),. Mais estudos são necessários, principalmente com um número maior de animais.

Obesity, a multifactorial disease, is disease, is defined as the excessive accumulation of adipose tissue in the body, being the most common nutritional disorder in dogs and cats, due, for the most part, to excessive food intake or inadequate use of energy, numerous studies indicate that the incidence of overweight/ obesity in canine population is constantly increasing, as well as its implications, the objective of the present study was to evaluate the effects of the administration of ultra-diluted and dynamized drugs in dogs with obesity. 38 dogs, both sexes, mostly mixed breed, between 2 and 13 years of age, all neutered, were evaluated. Weight, bodycondition score, body fat percentage, canine body mass index were evaluated, as well as abdominal and thoracic circumference and the thickness of adipose tissue in the region of the seventh lumbar vertebra by ultrasound examination. These assessments took place in two stages with an interval of 60 days between the beginning and end of the study, the animals were randomly divided into three groups, 10 animals belonging to the control group (GC), 15 animals belonging to the drug group A (DGA) and 13 animals belonging to the drug group B (GDB). The animals in the CG did not receive medication, while the animals in the other groups received 5 drops orally twice daily from the respective medication groups for 60 days. The medications were divided into two groups and named as medicine A (Calcarea carbonica 12cH + Fucus vesiculosos 6cH) and medicine B (Hyphotalamus 6cH + Leptin 8cH + Thyroidinum5CH). The results obtained in this study corroborate with other studies regarding the profile of the obese dog, where its highest incidence is in middle-age or elderly dogs, neutered animals, with high caloric diets and little physical activity, in addition to demonstrating that the animals treated with medicines Calcarea carbonica + Fucus vesiculosos, showed a reduction in the percentage of fat and waist circumference (p 0.05) and medicines Hyphotalamus + Leptin + Thyroidinum showed a reduction in body score (p 0.05). More studies are needed, especially with a larger number of animals.

Explorando os efeitos da leptina sobre a maturação in vitro de oócitos caprinos

A leptina é um hormônio proteico, produzido predominantemente pelo tecido adiposo, considerado sinal metabólico que regula os efeitos da nutrição na função reprodutiva. Em mamíferos, estudos tem demonstrado potencial papel direto da leptina na regulação da função ovariana e na maturação de oócitos. Os objetivos do presente estudo foram: investigar se a leptina recombinante (1, 10, 100 ng/mL) influencia a maturação meiótica de oócitos caprinos; se as vias JAK2/STAT3 e MAPK MEK1/2 medeiam os efeitos da leptina durante a maturação in vitro e como a leptina afeta a abundância de RNAm de genes relevantes para a transdução de sinal da leptina (PPAR, PPAR, AMPK1) e apoptose (Caspase 3, BAX e BCL2) em oócitos e células do cumulus. A adição de leptina, em todas as concentrações testadas, no meio de maturação afetou significativamente a porcentagem de oócitos que completaram a maturação nuclear. A maturação nuclear de oócitos estimulada pela leptina (10ng/mL) foi significativamente prejudicada quando os inibidores específicos de JAK2/STAT3 (AG490) e MEK 1/2 (U0126) foram adicionados ao meio de maturação. A adição de leptina (10ng/mL) durante a maturação não afetou a expressão dos genes PPAR, AMPK1, Caspase 3, BAX e BCL2 em oócitos ou células cumulus. O RNAm do PPAR nos oócitos foi significamente maior no grupo 10 ng/mL de leptina. Em conclusão, demonstramos que a leptina melhora a maturação meiótica de oócitos caprinos através das vias JAK2/STAT3 e MAPK MEK 1/2. Em adição, para oócitos submetidos à maturação in vitro em meio adicionado com 10 ng/mL de leptina, observamos maior expressão do PPAR no nível transcricional.

Leptin is a protein hormone, produced predominantly by adipose tissue, considered a metabolic signal that regulates the effects of nutrition on reproductive function. In mammals, studies have demonstrated the potential direct role of leptin in the regulation of ovarian function and in the maturation of oocytes. The objectives of the present study were: to investigate whether the recombinant leptin (1, 10, 100 ng / mL) influences the meiotic maturation of goat oocytes; whether the JAK2 / STAT3 and MAPK MEK1 / 2 pathways mediate the effects of leptin during in vitro maturation and how leptin affects the abundance of mRNAs relevant to leptin signal transduction (PPAR, PPAR, AMPK1) and apoptosis ( Caspase 3, BAX and BCL2) in oocytes and cumulus cells. The addition of leptin, in all concentrations tested, in the maturation medium significantly affected the percentage of oocytes that completed nuclear maturation. Nuclear oocyte maturation stimulated by leptin (10ng / mL) was significantly impaired when specific inhibitors of JAK2 / STAT3 (AG490) and MEK 1/2 (U0126) were added to the maturation medium. The addition of leptin (10ng / mL) during maturation did not affect the expression of the PPAR, AMPK1, Caspase 3, BAX and BCL2 genes in oocytes or cumulus cells. PPAR mRNA in oocytes was significantly higher in the 10 ng / mL leptin group. In conclusion, we demonstrated that leptin improves the meiotic maturation of goat oocytes through the JAK2 / STAT3 and MAPK MEK 1/2 pathways. In addition, for oocytes submitted to maturation in vitro in medium added with 10 ng / mL of leptin, we observed greater expression of PPAR at the transcriptional level.

Leptin and leptin receptor expressions in prostate tumors may predict disease aggressiveness?

The aim of this study was to evaluate the expression of leptin and its receptor in histological sections of prostate tumors, and their association with prognostic factors. A total of 532 surgical specimens from prostate cancer were studied. After histopathological diagnosis, the samples were included in tissue microarrays containing cores from tumor and non-tumor (benign prostatic hyperplasia) areas. These were immunostained with anti-leptin and anti-leptin-receptor antibodies. Objective and subjective analyses were performed. Student's-t-test and ANOVA were used to compare mean values, and linear regression was used to evaluate the correlation between histological results and prognostic indicators. Leptin receptor expression was reduced in tumors with a positive surgical margin, urethral margin involvement, and seminal vesicles invasion. Further, there was a negative correlation between the expression of leptin receptor in tumor areas and the sum of prognostic factors, suggesting that leptin receptor may predict the aggressiveness of disease. Our findings suggest that leptin receptor expression is a potential prognostic factor for PCa. Further investigation is needed to support the use of leptin receptor as a novel biomarker, although leptin itself does not seem to predict the aggressiveness of prostate cancer.(AU)

O papel da leptina na reprodução dos ruminantes / The role of leptin on the reproduction of ruminants

A leptina é um hormônio peptídico secretado principalmente pelo tecido adiposo, o qual promoveredução na ingestão de alimentos e no peso corporal. Atualmente, sabe-se que a leptina influencia o eixohipotalâmico-hipofisário e interfere em diversos processos fisiológicos em mamíferos. Porém, a maioria dasinformações existentes foi obtida com pesquisas realizadas em humanos e roedores. Desse modo, ainda não estáesclarecido o mecanismo de regulação em ruminantes. O objetivo desta revisão é sumarizar o papel da leptinasobre a reprodução de ruminantes, os mecanismos hormonais e sua ação ao longo da vida reprodutiva norebanho.(AU)

Leptin is a peptide hormone mainly secreted from the adipose tissue. It can cause marked reduction infood intake and body weight. At present, it is known that leptin influences the hypothalamic-pituitary axisinterfering in various physiological processes in mammals. However, the majority of the information existingwas obtained with research done in humans and rodents. Thus, the regulation mechanism in ruminants is stillunclear. The aim of this review was to outline the role of leptin in regulating reproduction in ruminants,hormone mechanism and its action on the flocks reproductive life.(AU)

O papel da leptina na reprodução dos ruminantes / The role of leptin on the reproduction of ruminants

A leptina é um hormônio peptídico secretado principalmente pelo tecido adiposo, o qual promoveredução na ingestão de alimentos e no peso corporal. Atualmente, sabe-se que a leptina influencia o eixohipotalâmico-hipofisário e interfere em diversos processos fisiológicos em mamíferos. Porém, a maioria dasinformações existentes foi obtida com pesquisas realizadas em humanos e roedores. Desse modo, ainda não estáesclarecido o mecanismo de regulação em ruminantes. O objetivo desta revisão é sumarizar o papel da leptinasobre a reprodução de ruminantes, os mecanismos hormonais e sua ação ao longo da vida reprodutiva norebanho.

Leptin is a peptide hormone mainly secreted from the adipose tissue. It can cause marked reduction infood intake and body weight. At present, it is known that leptin influences the hypothalamic-pituitary axisinterfering in various physiological processes in mammals. However, the majority of the information existingwas obtained with research done in humans and rodents. Thus, the regulation mechanism in ruminants is stillunclear. The aim of this review was to outline the role of leptin in regulating reproduction in ruminants,hormone mechanism and its action on the flock’s reproductive life.

EFEITO DA GORDURA CORPORAL NA EFICIÊNCIA REPRODUTIVA E VIABILIDADE EMBRIONÁRIA EM ÉGUAS DOADORAS DE EMBRIÃO DA RAÇA CRIOULA.

O cavalo Crioulo é originário dos cavalos espanhóis trazidos para a América. Estes animais se reproduziram livremente durante séculos, e hoje a raça apresenta grande impacto na equinocultura brasileira. A relação entre eficiência reprodutiva e obesidade têm sido relatada em espécies domésticas e em humanos, porém em equinos há poucos estudos, ainda não havendo relatos na raça Crioula. O objetivo deste trabalho foi investigar os efeitos do sobrepeso e/ou obesidade na eficiência reprodutiva e na qualidade embrionária de éguas da raça Crioula, doadoras de embrião. No experimento foram utilizadas 21 éguas, com histórico reprodutivo conhecido, sem alterações clínicas detectáveis, alojadas em uma central de reprodução no Sul do estado do Rio Grande do Sul. Foi verificado o escore corporal, avaliado de 1 à 9, e o acúmulo de gordura no pescoço, avaliado de 0 à 5. Foram coletadas amostras de sangue para avaliação dos níveis séricos de glicose e leptina. Não foi verificada associação entre o tamanho do folículo e o escore corporal (p=0,5835) ou acúmulo de gordura no p escoço (p=0,9153), enquanto houve forte correlação entre escore corporal e acúmulo de gordura no pescoço (p= <0,0001). Não há correlação linear entre tamanho do folículo e a leptina (p=0,5726). Foi realizada regressão logística para avaliar se o tamanho do folículo ou o escore corporal estavam associados a um lavado positivo, porém não houve associação com tamanho folicular (p=7609), nem o escore corporal (p=0,5482). Da mesma maneira não houve associação entre lavado positivo e as variáveis analisadas (p>0,05). Os resultados apresentados neste trabalho possuem grande importância para começarmos a compreender a relação entre eficiência reprodutiva e obesidade na raça Crioula.

The Crioulo horse originated from the Spanish horses brought to America. These animals have reproduced freely for centuries, and today the breed has great impact on Brazilian echinoculture. The relationship between reproductive efficiency and obesity has been reported in domestic species and human, but in equines there are few studies, although there are no reports in the Crioulo breed. The objective of this work was to investigate the effects of overweight and/or obesity on the reproductive efficiency and embryo quality of Crioulo breed embryo donor mares. In the experiment, 21 mares were used, with a known reproductive history,without detectable clinical alterations, housed in a center reproduction in the South of the state of Rio Grande do Sul. The body score are evaluated, from 1 to 9, and fat accumulation in the neck, evaluated from 0 to 5. Blood samples were collected for the evaluation of serum glucose and leptin levels. There are no association between follicle size and body score (p = 0.58 35) or accumulation of fat in the neck (p = 0.9153), while there was a strong correlation between body score and neck fat accumulation (p = <0.0001). There is no linear correlation between follicle size and leptin (p = 0.5726). Logistic regression was performed to assess whether follicle size or body score was associated with a positive wash, but there was no association with follicular size (p = 0.7609) or body score (p = 0.5482). Likewise, there was no association between positive lavage and the variables analyzed (p> 0.05). The results presented in this study are very important to begin to understand the relationship between reproductive efficiency and obesity in the Crioula breed.