RESUMO
Rice is the primary staple food for half of the world's population but is low in lysine content. Previously, we developed transgenic rice with enhanced free lysine content in rice seeds (lysine-rich rice), which was shown safe for consumption and improved the growth in rats. However, the effects of lysine-rich rice on skeletal growth and development remained unknown. In this study, we hypothesized that lysine-rich rice improved skeletal growth and development in weaning rats. Male weaning Sprague-Dawley rats received lysine-rich rice (HFL) diet, wild-type rice (WT) diet, or wild-type rice with various contents of lysine supplementation diet for 70 days. Bone microarchitectures were examined by microcomputed tomography, bone strength was investigated by mechanical test, and dynamics of bone growth were examined by histomorphometric analysis. In addition, we explored the molecular mechanism of lysine and skeletal growth through biochemical testing of growth hormone, bone turnover marker, and amino acid content of rat serum analysis, as well as in a cell culture system. Results indicated that the HFL diet improved rats' bone growth, strength, and microarchitecture compared with the WT diet group. In addition, the HFL diet increased the serum essential amino acids, growth hormone (insulin-like growth factor-1), and bone formation marker concentrations. The cell culture model showed that lysine deficiency reduced insulin-like growth factor-1 and Osterix expression, Akt/mammalian target of rapamycin signaling, and matrix mineralization, and inhibited osteoblast differentiation associated with bone growth. Our findings showed that lysine-rich rice improved skeletal growth and development in weaning rats. A further increase of rice lysine content is highly desirable to fully optimize bone growth and development.
Assuntos
Lisina , Oryza , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Oryza/genética , Oryza/metabolismo , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/metabolismo , Microtomografia por Raio-X , Peso Corporal , Hormônio do Crescimento/metabolismo , Mamíferos/metabolismoRESUMO
Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.
Assuntos
Diabetes Gestacional , Resistência à Insulina , Humanos , Gravidez , Feminino , Idoso , Lactogênio Placentário/metabolismo , Ácido Fólico , Prolactina , Alimentos Fortificados , Diabetes Gestacional/metabolismo , Estudos Prospectivos , Placenta/metabolismo , Hormônio do Crescimento/metabolismo , Glucose/metabolismoRESUMO
The bony skeleton, as a structural foundation for the human body, is essential in providing mechanical function and movement. The human skeleton is a highly specialized and dynamic organ that undergoes continuous remodeling as it adapts to the demands of its environment. Advances in research over the last decade have shone light on the various hormones that influence this process, modulating the metabolism and structural integrity of bone. More recently, novel and non-traditional functions of hypothalamic, pituitary, and adipose hormones and their effects on bone homeostasis have been proposed. This review highlights recent work on physiological bone remodeling and discusses our knowledge, as it currently stands, on the systemic interplay of factors regulating this interaction. In this review, we provide a summary of the literature on the relationship between bone physiology and hormones including kisspeptin, neuropeptide Y, follicle-stimulating hormone (FSH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), leptin, and adiponectin. The discovery and understanding of this new functionality unveils an entirely new layer of physiologic circuitry.
Assuntos
Hipotálamo , Hipófise , Humanos , Hipófise/metabolismo , Hipotálamo/metabolismo , Hormônio do Crescimento/metabolismo , Prolactina/metabolismo , Tireotropina/metabolismo , Tecido Adiposo/metabolismoRESUMO
Growth hormone (GH) action in specific neuronal populations regulates neuroendocrine responses, metabolism, and behavior. However, the potential role of central GH action on glial function is less understood. The present study aims to determine how the hypothalamic expression of several neuroglial markers is affected by central GH action in male mice. The dwarf GH- and insulin-like growth factor-1 (IGF-1)-deficient Ghrhrlit/lit mice showed decreased mRNA expression of Nes (Nestin), Gfap, Iba1, Adgre1 (F4/80), and Tnf (TNFα) in the hypothalamus, compared to wild-type animals. In contrast, transgenic overexpression of GH led to high serum GH and IGF-1 levels, and increased hypothalamic expression of Nes, Gfap, Adgre1, Iba1, and Rax. Hepatocyte-specific GH receptor (GHR) knockout mice, which are characterized by high serum GH levels, but reduced IGF-1 secretion, showed increased mRNA expression of Gfap, Iba1, Tnf, and Sox10, demonstrating that the increase in GH levels alters the hypothalamic expression of glial markers associated with neuroinflammation, independently of IGF-1. Conversely, brain-specific GHR knockout mice showed reduced expression of Gfap, Adgre1, and Vim (vimentin), indicating that brain GHR signaling is necessary to mediate GH-induced changes in the expression of several neuroglial markers. In conclusion, the hypothalamic mRNA levels of several neuroglial markers associated with inflammation are directly modulated by GHR signaling in male mice.
Assuntos
Hormônio do Crescimento , Fator de Crescimento Insulin-Like I , Camundongos , Masculino , Animais , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Hipotálamo/metabolismo , Camundongos Knockout , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
The toxicity of ammonia surged with arsenic pollution and high temperature (34 °C). As climate change enhances the pollution in water bodies, however, the aquatic animals are drastically affected and extinct from nature. The present investigation aims to mitigate arsenic and ammonia toxicity and high-temperature stress (As + NH3 + T) using zinc nanoparticles (Zn-NPs) in Pangasianodon hypophthalmus. Zn-NPs were synthesized using fisheries waste to developing Zn-NPs diets. The four isonitrogenous and isocaloric diets were formulated and prepared. The diets containing Zn-NPs at 0 (control), 2, 4 and 6 mg kg-1 diets were included. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-s-transferase (GST) were noticeably improved using Zn-NPs diets in fish reared under with or without stressors. Interestingly, lipid peroxidation was significantly reduced, whereas vitamin C and acetylcholine esterase were enhanced with supplementation of Zn-NPs diets. Immune-related attributes such as total protein, globulin, albumin, myeloperoxidase (MPO), A:G ratio, and NBT were also improved with Zn-NPs at 4 mg kg-1 diet. The immune-related genes such as immunoglobulin (Ig), tumor necrosis factor (TNFα), and interleukin (IL1b) were strengthening in the fish using Zn-NPs diets. Indeed, the gene regulations of growth hormone (GH), growth hormone regulator (GHR1), myostatin (MYST) and somatostatin (SMT) were significantly improved with Zn-NPs diets. Blood glucose, cortisol and HSP 70 gene expressions were significantly upregulated by stressors, whereas the dietary Zn-NPs downregulated the gene expression. Blood profiling (RBC, WBC and Hb) was reduced considerably with stressors (As + NH3 + T), whereas Zn-NPs enhanced the RBC, WBC, and Hb count in fish reread in control or stress conditions. DNA damage-inducible protein gene and DNA damage were significantly reduced using Zn-NPs at 4 mg kg-1 diet. Moreover, the Zn-NPs also enhanced the arsenic detoxification in different fish tissues. The present investigation revealed that Zn-NPs diets mitigate ammonia and arsenic toxicity, and high-temperature stress in P. hypophthalmus.
Assuntos
Arsênio , Peixes-Gato , Nanopartículas Metálicas , Animais , Antioxidantes/metabolismo , Zinco/metabolismo , Arsênio/toxicidade , Arsênio/metabolismo , Estresse Oxidativo , Amônia/metabolismo , Dieta/veterinária , Peixes-Gato/fisiologia , Hormônio do Crescimento/metabolismo , Imunidade Inata , Ração Animal/análise , Suplementos NutricionaisRESUMO
BACKGROUND: High-yielding dairy cows develop insulin resistance during late gestation associated with disruption of the growth hormone (GH)-insulin-like growth factor (IGF)-I axis and cause metabolic and reproductive disorders. OBJECTIVE: This study aimed to determine the effects of dietary pioglitazone (PIO) supplementation as an insulin sensitizer agent on milk yield, plasma metabolite status and GH-IGF-I axis in transition Holstein dairy cows. METHODS: Twenty multiparous cows were randomly assigned into two experimental groups (n = 10 animals per group) and either fed with a basal diet (control) or the basal diet supplemented with 6 mg PIO/kg body weight (BW) from day 14 before parturition to day 21 postpartum. The BW and body condition score (BCS), non-esterified fatty acids, beta-hydroxybutyrate (BHBA), insulin, glucose, GH and IGF-I concentrations, milk production and composition were measured weekly. RESULTS: BW and BCS losses were lower in PIO than in control cows (p < 0.05). The percentage and amount of milk fat were decreased, and the amount of protein increased only in the first post-calving week in the PIO-treated cows compared to the control (p < 0.05). Dietary PIO supplementation increased glucose concentration at calving, but insulin concentration was increased at calving and in the first post-calving week (p < 0.05). Plasma concentrations of IGF-I and the ratio of IGF to GH were increased in the PIO group (p < 0.05). The mean revised quantitative insulin sensitivity check index with BHBA, as an insulin sensitivity index, was greater in PIO-supplemented cows (p < 0.05). CONCLUSIONS: Our results showed beneficial effects of PIO supplementation on improving insulin sensitivity and the GH-IGF-I axis that may cause lower negative energy balance and better metabolic and health status in transition dairy cows.
Assuntos
Doenças dos Bovinos , Resistência à Insulina , Feminino , Gravidez , Bovinos , Animais , Leite/metabolismo , Pioglitazona/metabolismo , Pioglitazona/farmacologia , Lactação , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Suplementos Nutricionais , Insulina/metabolismo , Insulina/farmacologia , Glucose/metabolismo , Glucose/farmacologiaRESUMO
OBJECTIVE: Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth requiring lipid supplementation. Lipids are targets of reactive oxygen species resulting in lipid peroxidation and cell death, particularly in preterm infants with compromised antioxidant systems. We tested the hypothesis that early supplementation with lipids and/or antioxidants promotes growth and influences biomarkers of carbohydrate metabolism in neonatal rats exposed to IH. DESIGN: Newborn rats (n = 18/group) were exposed to brief hypoxia (12% O2) during hyperoxia (50% O2), or room air (RA), from birth (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) glutathione nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At P21, plasma samples were assessed for glucose, insulin, glucokinase (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), corticosterone, and ghrelin. Liver was assessed for histopathology, apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL stain), and GH, insulin-like growth factor (IGF)-I, GH binding protein (GHBP), and IGF binding protein (IGFBP)-3. RESULTS: Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10 + fish oil, while corticosterone was higher with nGSH and CoQ10 + fish oil. IGF-I and IGFBP-3 were significantly higher in the liver with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10 + fish oil reduced IGF-I in RA and IH but increased IGFBP-3. CONCLUSIONS: Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and carbohydrate metabolism. Data suggest that these supplements may improve poor postnatal organ and body growth; and metabolic dysfunction associated with neonatal IH.
Assuntos
Hormônio do Crescimento Humano , Insulinas , Recém-Nascido , Humanos , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Animais Recém-Nascidos , Grelina , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Óleos de Peixe/farmacologia , Glucagon/metabolismo , Glicemia , Corticosterona , Azeite de Oliva , Recém-Nascido Prematuro , Hipóxia/complicações , Suplementos Nutricionais , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/metabolismo , Metabolismo dos Carboidratos , Biomarcadores/metabolismo , Insulinas/metabolismoRESUMO
BACKGROUND: The pollution and climate change in aquatic ecosystems are major problems threatening the aquatic organisms for existence in the recent timeline, which promotes the extinction of the fish species. However, the present study dealt with zinc nanoparticles (Zn-NPs) in mitigating arsenic, ammonia and high temperature stresses in Pangasianodon hypophthalmus. MATERIALS AND METHODS: To studying different gene expressions, an experiment was conducted to mitigate the multiple stressors using dietary Zn-NPs at 0, 2, 4, and 6 mg kg-1 diets. In the present investigation, the gene expressions studies were performed for growth hormone regulator 1 (GHR1), growth hormone regulator ß (GHRß), growth hormone (GR) in liver and gill tissue as well as myostatin (MYST) and somatostatin (SMT) in the muscle tissue. The anti-oxidative genes CAT, SOD and GPx in liver and gill tissues were also analysed. Expression studies for stress responsive heat shock protein gene (HSP70), DNA damage inducible protein, inducible nitric oxide synthase (iNOS), immune related genes such as interleukin (IL), tumour necrosis factor (TNFα), toll like receptor (TLR) and immunoglobulin were performed. At the end of the experiment the fish were infected with Aeromonas hydrophila to evaluate the immunomodulatory role of Zn-NPs. RESULTS: In the present investigation, the growth hormone regulator 1 (GHR1), growth hormone regulator ß (GHRß), growth hormone (GR) in liver and gill as well as myostatin (MYST) and somatostatin (SMT) in muscle were noticeably altered, whereas, Zn-NPs at 4 mg kg-1 diet improved gene expressions. The anti-oxidant gene viz. CAT, SOD and GPx in liver and gill tissues were upregulated by stressors such as As, NH3, NH3+T. As+T and As+NH3+T. Therefore, anti-oxidant genes were noticeably improved with dietary Zn-NPs diet. The stress protein gene (HSP70), DNA damage inducible protein, inducible nitric oxide synthase (iNOS) was significantly upregulated, whereas, Zn-NPs diet was applied to the corrected gene regulation. Similarly, immune related genes such as interleukin (IL), tumour necrosis factor (TNFα), toll like receptor (TLR) and immunoglobulin were highly affected by stressors. Dietary Zn-NPs at 4 mg kg-1 diet was improved all the immune related gene expression and mitigate arsenic, ammonia and high temperature stress in fish. CONCLUSION: The present investigation revealed that Zn-NPs at 4.0 mg kg-1 diet has enormous potential to modulates arsenic, ammonia and high temperature stress, and protect against pathogenic infections in fish.
Assuntos
Arsênio , Peixes-Gato , Nanopartículas Metálicas , Amônia , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Arsênio/metabolismo , Dieta , Suplementos Nutricionais/análise , Ecossistema , Hormônio do Crescimento/metabolismo , Proteínas de Choque Térmico/metabolismo , Miostatina/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Somatostatina/metabolismo , Superóxido Dismutase/metabolismo , Temperatura , Fator de Necrose Tumoral alfa/metabolismo , Zinco/metabolismo , Zinco/farmacologiaRESUMO
Growth hormone (GH)-responsive neurons regulate several homeostatic behaviors including metabolism, energy balance, arousal, and stress response. Therefore, it is possible that GH-responsive neurons play a role in other responses such as CO2/H+-dependent breathing behaviors. Here, we investigated whether central GH receptor (GHR) modulates respiratory activity in conscious unrestrained mice. First, we detected clusters of GH-responsive neurons in the tyrosine hydroxylase-expressing cells in the rostroventrolateral medulla (C1 region) and within the locus coeruleus (LC). No significant expression was detected in phox2b-expressing cells in the retrotrapezoid nucleus. Whole body plethysmography revealed a reduction in the tachypneic response to hypoxia (FiO2 = 0.08) without changing baseline breathing and the hypercapnic ventilatory response. Contrary to the physiological findings, we did not find significant differences in the number of fos-activated cells in the nucleus of the solitary tract (NTS), C1, LC and paraventricular nucleus of the hypothalamus (PVH). Our finding suggests a possible secondary role of central GH action in the tachypneic response to hypoxia in conscious mice.
Assuntos
Hipercapnia , Núcleo Solitário , Animais , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Hipóxia/metabolismo , Camundongos , Núcleo Solitário/metabolismoRESUMO
Growth hormone (GH) acts in several hypothalamic neuronal populations to modulate metabolism and the autoregulation of GH secretion via negative-feedback loops. However, few studies have investigated whether GH receptor (GHR) expression in specific neuronal populations is required for the homeostatic control of GH secretion and energy homeostasis. In the present study, we investigated the consequences of the specific GHR ablation in GABAergic (VGAT-expressing) or glutamatergic (VGLUT2-expressing) cells. GHR ablation in GABAergic neurons led to increased GH secretion, lean mass, and body growth in male and female mice. VGAT-specific GHR knockout (KO) male mice also showed increased serum insulin-like growth factor-1, hypothalamic Ghrh, and hepatic Igf1 messenger RNA levels. In contrast, normal GH secretion, but reduced lean body mass, was observed in mice carrying GHR ablation in glutamatergic neurons. GHR ablation in GABAergic cells increased weight loss and led to decreased blood glucose levels during food restriction, whereas VGLUT2-specific GHR KO mice showed blunted feeding response to 2-deoxy-D-glucose both in males and females, and increased relative food intake, oxygen consumption, and serum leptin levels in male mice. Of note, VGLUT2-cre female mice, independently of GHR ablation, exhibited a previously unreported phenotype of mild reduction in body weight without further metabolic alterations. The autoregulation of GH secretion via negative-feedback loops requires GHR expression in GABAergic cells. Furthermore, GHR ablation in GABAergic and glutamatergic neuronal populations leads to distinct metabolic alterations. These findings contribute to the understanding of the neuronal populations responsible for mediating the neuroendocrine and metabolic effects of GH.
Assuntos
Neurônios GABAérgicos , Receptores da Somatotropina , Animais , Feminino , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Receptores para Leptina/metabolismo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismoRESUMO
AIMS: The present study aims to compare the responses between male and female C57BL/6 mice to multiple metabolic challenges to understand the importance of sex in the control of energy homeostasis. MAIN METHODS: Male and female C57BL/6 mice were subjected to nutritional and hormonal challenges, such as food restriction and refeeding, diet-induced obesity, feeding response to ghrelin and leptin, ghrelin-induced growth hormone secretion, and central responsiveness to ghrelin and leptin. The hypothalamic expression of transcripts that control energy homeostasis was also evaluated. KEY FINDINGS: Male mice lost more weight and lean body mass in response to food restriction, compared to females. During refeeding, males accumulated more body fat and exhibited lower energy expenditure and glycemia, as compared to females. Additionally, female mice exhibited a higher protection against diet-induced obesity and related metabolic imbalances in comparison to males. Low dose ghrelin injection elicited higher food intake and growth hormone secretion in male mice, whereas the acute anorexigenic effect of leptin was more robust in females. However, the sex differences in the feeding responses to ghrelin and leptin were not explained by variations in the central responsiveness to these hormones nor by differences in the fiber density from arcuate nucleus neurons. Female, but not male, mice exhibited compensatory increases in hypothalamic Pomc mRNA levels in response to diet-induced obesity. SIGNIFICANCE: Our findings revealed several sexually differentiated responses to metabolic challenges in C57BL/6 mice, highlighting the importance of taking into account sex differences in metabolic studies.
Assuntos
Grelina , Leptina , Animais , Feminino , Grelina/farmacologia , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismoRESUMO
Links between the regulation of growth and energy balance are clear; to fuel growth, there must be consumption of energy. Therefore, it is perhaps intuitive that interactions between the hypothalamic - pituitary - growth hormone axis (growth axis) and pathways that drive metabolic processes exist. Overproduction of growth hormone has been associated with diabetes and metabolic disease for decades and the opposing effects of growth hormone and insulin have been studied since early experiments almost a century ago. The relationship between neuroendocrine axes can be complex and the growth axis is no exception, interacting with energy balance in several organ systems, both in the periphery and centrally in hypothalamic nuclei. Much is known about peripheral interactions between growth axis hormones and processes such as glucose homeostasis and adipogenesis. More is still being learned about the molecular actions of growth axis hormones in adipose and other metabolically active tissues, and recent findings are discussed in this perspective. However, less is known about interactions with central energy balance pathways in the hypothalamus. This perspective aims to summarise what is known about these interactions, taking lessons from human studies and animal genetic and seasonal models, and discusses what this may mean in an evolving landscape of personalised medicine.
Assuntos
Apetite , Hormônio do Crescimento Humano , Animais , Metabolismo Energético/fisiologia , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/metabolismo , Hipotálamo/metabolismo , Sistemas Neurossecretores/metabolismoRESUMO
INTRODUCTION: While the vast majority of research investigating the role of ghrelin or its receptor, GHS-R1a, in growth, feeding, and metabolism has been conducted in male rodents, very little is known about sex differences in this system. Furthermore, the role of GHS-R1a signaling in the control of pulsatile GH secretion and its link with growth or metabolic parameters has never been characterized. METHODS: We assessed the sex-specific contribution of GHS-R1a signaling in the activity of the GH/IGF-1 axis, metabolic parameters, and feeding behavior in adolescent (5-6 weeks old) or adult (10-19 weeks old) GHS-R KO (Ghsr-/-) and WT (Ghsr+/+) male and female mice. RESULTS: Adult Ghsr-/- male and female mice displayed deficits in weight and linear growth that were correlated with reduced GH pituitary contents in males only. GHS-R1a deletion was associated with reduced meal frequency and increased meal intervals, as well as reduced hypothalamic GHRH and NPY mRNA in males, not females. In adult, GH release from Ghsr-/- mice pituitary explants ex vivo was reduced independently of the sex. However, in vivo pulsatile GH secretion decreased in adult but not adolescent Ghsr-/- females, while in males, GHS-R1a deletion was associated with reduction in pulsatile GH secretion during adolescence exclusively. In males, linear growth did not correlate with pulsatile GH secretion, but rather with ApEn, a measure that reflects irregularity of the rhythmic secretion. Fat mass, plasma leptin concentrations, or ambulatory activity did not predict differences in GH secretion. DISCUSSION/CONCLUSION: These results point to a sex-dependent dimorphic effect of GHS-R1a signaling to modulate pulsatile GH secretion and meal pattern in mice with different compensatory mechanisms occurring in the hypothalamus of adult males and females after GHS-R1a deletion. Altogether, we show that GHS-R1a signaling plays a more critical role in the regulation of pulsatile GH secretion during adolescence in males and adulthood in females.
Assuntos
Grelina , Receptores de Grelina/metabolismo , Animais , Comportamento Alimentar , Feminino , Grelina/metabolismo , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Masculino , Camundongos , Hipófise/metabolismo , Receptores de Grelina/genéticaRESUMO
Growth hormone (GH) is one of the critical factors in maintaining glucose metabolism. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are key regulators of diverse metabolic processes. In this study, we investigated the link between GH and BTG2-YY1 signaling pathway in glucose metabolism. GH treatment elevated the expression of hepatic Btg2 and Yy1 in primary mouse hepatocytes and mouse livers. Glucose production in primary mouse hepatocytes and serum blood glucose levels were increased during GH exposure. Overexpression of hepatic Btg2 and Yy1 induced key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6 phosphatase (G6PC) as well as glucose production in primary mouse hepatocytes, whereas this phenomenon was markedly diminished by knockdown of Btg2 and Yy1. Here, we identified the YY1-binding site on the Pck1 and G6pc gene promoters using reporter assays and point mutation analysis. The regulation of hepatic gluconeogenic genes induced by GH treatment was clearly linked with YY1 recruitment on gluconeogenic gene promoters. Overall, this study demonstrates that BTG2 and YY1 are novel regulators of GH-dependent regulation of hepatic gluconeogenic genes and glucose production. BTG2 and YY1 may be crucial therapeutic targets to intervene in metabolic dysfunction in response to the GH-dependent signaling pathway.
Assuntos
Gluconeogênese/genética , Hormônio do Crescimento/metabolismo , Proteínas Imediatamente Precoces/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Fator de Transcrição YY1/metabolismo , Animais , Linhagem Celular , Glucose/biossíntese , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Hormônio do Crescimento/administração & dosagem , Hepatócitos , Humanos , Injeções Intraperitoneais , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Modelos Animais , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Mutação Puntual , Cultura Primária de Células , Regiões Promotoras Genéticas , Transdução de Sinais/genéticaRESUMO
Inflammation induces a wide response of the neuroendocrine system, which leads to modifications in all the endocrine axes. The hypothalamic-growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis is deeply affected by inflammation, its response being characterized by GH resistance and a decrease in circulating levels of IGF-1. The endocrine and metabolic responses to inflammation allow the organism to survive. However, in chronic inflammatory conditions, the inhibition of the hypothalamic-GH-IGF-1 axis contributes to the catabolic process, with skeletal muscle atrophy and cachexia. Here, we review the changes in pituitary GH secretion, IGF-1, and IGF-1 binding protein-3 (IGFBP-3), as well as the mechanism that mediated those responses. The contribution of GH and IGF-1 to muscle wasting during inflammation has also been analyzed.
Assuntos
Caquexia/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Caquexia/fisiopatologia , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/metabolismo , Humanos , Hipotálamo/metabolismo , Inflamação/fisiopatologia , Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologiaRESUMO
SCOPE: Dietary intervention to obese dams during pregnancy and lactation period provides avenues for improving metabolic profiles of the offspring. In the current study, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to obese dams during pregnancy and lactation on the skeletal outcomes of male offspring are investigated. METHODS AND RESULTS: MFGM-PL is supplemented to obese rats induced by high-fat diet during pregnancy and lactation at a dose of 400 mg kg-1 body weight. Results show that maternal MFGM-PL supplementation significantly ameliorates the stunted skeletal growth of male offspring at weaning. In adulthood offspring, maternal MFGM-PL supplementation protects against high-fat diet (HFD)-induced bone microstructure degeneration and bone marrow adipocyte accumulation. Further investigation shows that maternal supplementation of MFGM-PL significantly ameliorates insulin resistance and increases the mRNA expression of growth hormone releasing hormone (GHRH) in the hypothalamus of HFD offspring. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is subsequently enhanced in MFGM-PL + HFD offspring, contributing to the beneficial skeletal outcomes. CONCLUSION: The findings suggest that maternal MFGM-PL supplementation of HFD dam during pregnancy and lactation shows desirable effects on fetal skeletal development, with lasting beneficial programming impacts on skeletal outcomes of offspring.
Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Glicolipídeos/farmacologia , Glicoproteínas/farmacologia , Resistência à Insulina , Obesidade/dietoterapia , Animais , Desenvolvimento Ósseo/fisiologia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Feminino , Glicolipídeos/química , Glicoproteínas/química , Hormônio Liberador de Gonadotropina/genética , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lactação , Gotículas Lipídicas/química , Lipídeos/química , Lipídeos/farmacologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Leite/química , Obesidade/fisiopatologia , Gravidez , Ratos Sprague-DawleyRESUMO
Chronic stress exerts multiple negative effects on the physiology and health of an individual. In the present study, we examined hypothalamic, pituitary and endocrine responses to 14 days of chronic variable stress (CVS) in male and female C57BL/6J mice. In both sexes, CVS induced a significant decrease in body weight and enhanced the acute corticosterone stress response, which was accompanied by a reduction in thymus weight only in females. However, single-point blood measurements of basal prolactin, thyroid-stimulating hormone, luteinising hormone, growth hormone and corticosterone levels taken at the end of the CVS were not different from those of controls. Similarly, pituitary mRNA expression of Fshb, Lhb, Prl and Gh was unchanged by CVS, although Pomc and Tsh were significantly elevated. Within the adrenal medulla, mRNA for Th, Vip and Gal were elevated following CVS. Avp transcript levels within the paraventricular nucleus of the hypothalamus were increased by CVS; however, levels of Gnrh1, Crh, Oxt, Sst, Trh, Ghrh, Th and Kiss1 remained unchanged. Oestrous cycles were lengthened slightly by CVS and ovarian histology revealed a reduction in the number of preovulatory follicles and corpora lutea. Taken together, these observations indicate that 14 days of CVS induces an up-regulation of the neuroendocrine stress axis and creates a mild disruption of female reproductive function. However, the lack of changes in other neuroendocrine axes controlling anterior and posterior pituitary secretion suggest that most neuroendocrine axes are relatively resilient to CVS.
Assuntos
Hipotálamo/metabolismo , Folículo Ovariano/metabolismo , Hipófise/metabolismo , Pró-Opiomelanocortina/metabolismo , Estresse Psicológico/metabolismo , Animais , Corpo Lúteo/metabolismo , Corticosterona/metabolismo , Feminino , Hormônio do Crescimento/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Camundongos , Neurônios/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Prolactina/metabolismo , Tireotropina/metabolismoRESUMO
Central actions of leptin and insulin on hepatic lipid metabolism can be opposing and the mechanism underlying this phenomenon remains unclear. Both hormones can modulate the central somatostatinergic system that has an inhibitory effect on growth hormone (GH) expression, which plays an important role in hepatic metabolism. Using a model of chronic central leptin infusion, we evaluated whether an increase in central leptin bioavailability modifies the serum lipid pattern through changes in hepatic lipid metabolism in male rats in response to an increase in central insulin and the possible involvement of the GH axis in these effects. We found a rise in serum GH in leptin plus insulin-treated rats, due to an increase in pituitary GH mRNA levels associated with lower hypothalamic somatostatin and pituitary somatostatin receptor-2 mRNA levels. An augment in hepatic lipolysis and a reduction in serum levels of non-esterified fatty acids (NEFA) and triglycerides were found in leptin-treated rats. These rats experienced a rise in lipogenic-related factors and normalization of serum levels of NEFA and triglycerides after insulin treatment. These results suggest that an increase in insulin in leptin-treated rats can act on the hepatic lipid metabolism through activation of the GH axis.
Assuntos
Hipotálamo/efeitos dos fármacos , Insulina/farmacologia , Leptina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Animais , Ácidos Graxos não Esterificados/sangue , Regulação da Expressão Gênica , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Injeções Intravenosas , Injeções Intraventriculares , Insulina/metabolismo , Leptina/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Masculino , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transdução de Sinais , Triglicerídeos/sangueRESUMO
The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/genética , Leptina/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Metabolismo Energético/genética , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hormônio do Crescimento/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraventriculares , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Somatostatina/genética , Somatostatina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
This study aims to evaluate the effect of puerarin on performance, meat quality, and serum indexes of beef cattle under hot environment. Thirty-two bulls were divided into four groups and fed diet supplemented with puerarin at 0, 200, 400, or 800 mg/kg. Results showed that heat stress was employed for 54 out of 60 days, 400 mg/kg group declined serum cortisol (COR) contents, all treatments increased the contents of total cholesterol, high density lipoprotein cholesterol, and total superoxide dismutase activity; in addition, glutathione peroxidase activity of 200 mg/kg group were enhanced, only 800 mg/kg group enhanced immunoglobulin (IgA, IgM, and IgG) and low density lipoprotein cholesterol contents compared with the control (p < .05). Moreover, 400-mg/kg puerarin increased serum growth hormone levels compared with 200 mg/kg group but declined COR concentrations compared with 200 mg/kg and 800 mg/kg groups (p < .05). More importantly, average daily gain and daily matter intake, and intramuscular fat contents of 400 mg/kg group were enhanced, but the shear force of beef in 400 mg/kg and 800 mg/kg groups were declined compared with the control (p < .05). These findings indicated that supplemental with puerarin enhanced immune and antioxidant, and 400 mg/kg of puerarin improved performance and meat quality by normalizing levels of stress hormones and increasing intramuscular fat deposition of beef cattle under hot environment.