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1.
Cell Physiol Biochem ; 53(5): 851-864, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714043

RESUMO

BACKGROUND/AIMS: The growth promoting effect of lysine and betaine as well as the expression of candidate genes reflecting their efficacy, such as ghrelin, leptin, Growth Hormone Secretagogue Receptor (GHS-R), Insulin like Growth Factor (IGF- 1) and Growth Hormone Releasing Hormone (GHRH) was examined in Labeo rohita fingerlings. METHODS: One hundred eighty healthy juveniles from a homologous population were randomly distributed to 15 rectangular tanks of 150 litres capacity. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. At the end of trial, the growth parameters such as weight gain, SGR, PER were estimated from the weight of the triplicate groups. The digestive, metabolic and antioxidant enzymes were analysed using spectrophotometric methods. The intestine, brain and liver were sampled from the treatments and expression of different genes ghrelin, leptin, GHSR, IGF-1 and GHRH was also performed by realtime PCR. RESULTS: A significant (P<0.05) increase in weight gain, SGR, PER and lowest FCR was found in T4 group which was significantly (p < 0.05) different from other experimental groups. The highest mRNA expression levels of expression were found in T4 group which was similar to that of ghrelin gene mRNA of T2 group. The significantly (p<0.05) highest GHSR, GHRH and IGF-1 gene expression levels were found in T4 treatment group compared to other groups. CONCLUSION: The present study reveals that the lysine and betaine stimulate growth and expression of ghrelin GHRH, GHS-R and IGF-1 genes. The increase of IGF-I mRNA expression with lysine and betaine supplementation revealed that these compounds act as growth modulators. However, lysine was found to be a more potent modulator of growth compared to betaine.


Assuntos
Betaína/farmacologia , Cyprinidae/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lisina/farmacologia , Ração Animal , Animais , Catalase/metabolismo , Cyprinidae/crescimento & desenvolvimento , Grelina/genética , Grelina/metabolismo , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Leptina/genética , Leptina/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Superóxido Dismutase/metabolismo
2.
Orv Hetil ; 160(44): 1727-1734, 2019 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-31657254

RESUMO

Authors discuss the musculoskeletal aspects of obesity by applying a novel approach. Biochemical changes associated with obesity and especially metabolic syndrome, may have a great impact on the function of bones, joints and muscles. Therefore we need a new view and new strategies in rheumatic diseases. Obesity-associated metabolic changes should be considered during the progress of as well as the selection of treatment in inflammatory rheumatic diseases. Individualised treatment is necessary due to associated comorbidities as well. Orv Hetil. 2019; 160(44): 1727-1734.


Assuntos
Artropatias/etiologia , Artropatias/fisiopatologia , Síndrome Metabólica , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Doenças Reumáticas , Adipocinas/metabolismo , Artrite , Humanos , Artropatias/metabolismo , Leptina/metabolismo , Doenças Musculoesqueléticas/metabolismo , Obesidade/metabolismo , Osteoartrite/etiologia , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Doenças Reumáticas/etiologia , Doenças Reumáticas/metabolismo , Doenças Reumáticas/fisiopatologia
3.
Res Vet Sci ; 125: 360-369, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31376718

RESUMO

Alpha-tocopherol-selenium (ATS) and ascorbic acid (AA) are the potent antioxidants. The present study investigated whether supplementation of ATS and AA in periparturient sows has positive effects on amelioration of oxidative stress, serum immunoglobulin G (IgG), lipid profile and sows performance. For this, twenty-four pregnant multiparous sows (landrace×indigenous) were randomly distributed into four groups (6 sows per group) 20 days before expected date of farrowing as Control (basal diet); ATS (basal diet + ATS); AA (basal diet + AA) and ATS-AA (basal diet + ATS plus AA). The results of the study revealed that the concentrations of triglyceride and cholesterol significantly reduced from day -7 to day 7 of farrowing irrespective of supplementations to sows, but the leptin concentration significantly reduced on day 7 of farrowing in ATS-AA supplemented sows (p<0.05). Moreover, sows of supplemented groups experienced decreased oxidative stress and cortisol level than control sows. The serum IgG concentration was significantly increased on day 7 post-farrowing in ATS group but it was much earlier on day 2 of farrowing in ATS-AA group (p<0.001). Supplementing sows with ATS and/or AA did not influence significantly the birth weight, weaning weight and litter size at weaning (p>0.05). Although piglet survival rate was not affected significantly by supplementation, however, piglet mortality rate was lowest in ATS-AA than any other groups. It was concluded that supplementation of ATS and/or AA to sows during late gestating and early lactating period ameliorated oxidative stress, improved lipid profile and serum IgG level without influencing reproductive performance.


Assuntos
Ácido Ascórbico/metabolismo , Metabolismo dos Lipídeos , Estresse Oxidativo , Selênio/metabolismo , Sus scrofa/fisiologia , alfa-Tocoferol/metabolismo , Ração Animal/análise , Animais , Animais Recém-Nascidos/fisiologia , Ácido Ascórbico/administração & dosagem , Contagem de Células Sanguíneas/veterinária , Peso Corporal , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Lactação , Leptina/metabolismo , Tamanho da Ninhada de Vivíparos , Longevidade , Gravidez , Selênio/administração & dosagem , alfa-Tocoferol/administração & dosagem
4.
Hypertension ; 74(3): 678-686, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327274

RESUMO

Compelling clinical evidence indicates that obesity and its associated metabolic abnormalities supersede the protective effects of female sex-hormones and predisposes premenopausal women to cardiovascular disease. The underlying mechanisms remain poorly defined; however, recent studies have implicated overactivation of the aldosterone-MR (mineralocorticoid receptor) axis as a cause of sex-specific cardiovascular risk in obese females. Experimental evidence indicates that the MR on endothelial cells contributes to obesity-associated, leptin-induced endothelial dysfunction in female experimental models, however, the vascular-specific mechanisms via which females are predisposed to heightened endothelial MR activation remain unknown. Therefore, we hypothesized that endogenous expression of endothelial MR is higher in females than males, which predisposes them to obesity-associated, leptin-mediated endothelial dysfunction. We found that endothelial MR expression is higher in blood vessels from female mice and humans compared with those of males, and further, that PrR (progesterone receptor) activation in endothelial cells is the driving mechanism for sex-dependent increases in endothelial MR expression in females. In addition, we show that genetic deletion of either the endothelial MR or PrR in female mice prevents leptin-induced endothelial dysfunction, providing direct evidence that interaction between the PrR and MR mediates obesity-associated endothelial impairment in females. Collectively, these novel findings suggest that progesterone drives sex-differences in endothelial MR expression and predisposes female mice to leptin-induced endothelial dysfunction, which indicates that MR antagonists may be a promising sex-specific therapy to reduce the risk of cardiovascular diseases in obese premenopausal women.


Assuntos
Endotélio Vascular/patologia , Regulação da Expressão Gênica , Obesidade/fisiopatologia , Progesterona/metabolismo , Receptores de Mineralocorticoides/genética , Animais , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Feminino , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Obesidade/genética , Distribuição Aleatória , Medição de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Regulação para Cima
5.
Nat Commun ; 10(1): 2717, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222048

RESUMO

Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis.


Assuntos
Leptina/metabolismo , Fígado/metabolismo , Bulbo/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Infusões Intraventriculares , Injeções Intraventriculares , Leptina/administração & dosagem , Lipogênese/fisiologia , Lipoproteínas VLDL , Fígado/inervação , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Polietilenoglicóis/administração & dosagem , Ratos , Ratos Sprague-Dawley , Técnicas Estereotáxicas , Simpatectomia , Nervo Vago/fisiologia , Nervo Vago/cirurgia
6.
J Agric Food Chem ; 67(25): 7040-7049, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199141

RESUMO

Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first induced to develop obesity by being fed a high-fat diet. The obese rats were then fed a control diet, AIN-93M (group HFD), or a 10% FP diet (group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, and serous proteins within the leptin-neuropeptide Y (NPY) and AMP-activated protein kinase (AMPK) signaling pathway were determined and analyzed. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15% ± 0.30% in group HFD to 478 ± 10 g and 1.38% ± 0.48% in group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Linho/química , Leptina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Saciação/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Obesidade/metabolismo , Obesidade/psicologia , Extratos Vegetais/química , Polissacarídeos/química , Ratos , Ratos Wistar , Sementes/química , Transdução de Sinais/efeitos dos fármacos
7.
Vet Surg ; 48(5): 780-785, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31155740

RESUMO

OBJECTIVE: To evaluate the relationship between serum and synovial fluid (SF) leptin concentrations and body condition score (BCS) in healthy and osteoarthritic dogs. STUDY DESIGN: Controlled, prospective, clinical study. ANIMALS: Nineteen healthy dogs and 29 dogs with osteoarthritis (OA) secondary to cranial cruciate ligament injury. METHODS: Synovial fluid was obtained from the femorotibial joint under sedation (healthy dogs) or during surgery (OA dogs). Serum and SF leptin and interleukin (IL)-1ß concentrations were measured via enzyme-linked immunosorbent assay. Dogs were classified as optimal weight (BCS 4-5/9) or overweight (BCS >5/9). Radiographs were scored for OA severity by a radiologist. Owners completed the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire. RESULTS: Mean (± SD) SF leptin (4.09 ± 4 ng/mL) was lower than serum leptin (6.88 ± 5.52 ng/mL, P < .0001). Synovial fluid leptin was higher in overweight (5.28 ± 4.21) than in optimal body weight dogs (1.54 ± 1.72 ng/mL, P < .0001). Serum (P < .001) and SF leptin (P = .004) concentrations were associated with BCS. Concentration of SF leptin did not differ between healthy (2.4 ± 2.04 ng/mL) and OA (4.9 ± 4.3 ng/mL, P = .25) dogs. Synovial fluid leptin and LOAD scores were weakly associated (P = .03). No association was detected between SF leptin and radiographic score or IL-1ß (P = .73). CONCLUSION: Serum and SF leptin correlated with BCS in this population. Synovial fluid leptin was weakly associated with LOAD scores but not with radiographic severity of OA or IL-1ß. CLINICAL SIGNIFICANCE: Serum and SF leptin concentrations do not predict radiographic severity of canine OA but contribute to joint pain and dysfunction.


Assuntos
Composição Corporal , Doenças do Cão/metabolismo , Leptina/sangue , Osteoartrite/veterinária , Líquido Sinovial/química , Animais , Lesões do Ligamento Cruzado Anterior/sangue , Lesões do Ligamento Cruzado Anterior/metabolismo , Lesões do Ligamento Cruzado Anterior/veterinária , Doenças do Cão/sangue , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leptina/análise , Leptina/metabolismo , Masculino , Osteoartrite/sangue , Osteoartrite/metabolismo , Estudos Prospectivos , Radiografia
8.
Life Sci ; 232: 116575, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211999

RESUMO

AIMS: Maternal smoking is considered a risk factor for childhood obesity. In a rat model of tobacco exposure during breastfeeding, we previously reported hyperphagia, overweight, increased visceral fat and hyperleptinemia in adult female offspring. Obesity and eating disorders are associated with impairment in the endocannabinoid (EC) and dopaminergic (DA) systems. Considering that women are prone to eating disorders, we hypothesize that adult female Wistar rats that were exposed to cigarette smoke (CS) during the suckling period would develop EC and DA systems deregulation, possibly explaining the eating disorder in this model. MATERIAL AND METHODS: To mimic maternal smoking, from postnatal day 3 to 21, dams and offspring were exposed to a smoking machine, 4×/day/1 h (CS group). Control animals were exposed to ambient air. Offspring were evaluated at 26 weeks of age. KEY FINDINGS: Concerning the EC system, the CS group had increased expression of diacylglycerol lipase (DAGL) in the lateral hypothalamus (LH) and decreased in the liver. In the visceral adipose tissue, the EC receptor (CB1r) was decreased. Regarding the DA system, the CS group showed higher dopamine transporter (DAT) protein expression in the prefrontal cortex (PFC) and lower DA receptor (D2r) in the arcuate nucleus (ARC). We also assessed the hypothalamic leptin signaling, which was shown to be unchanged. CS offspring showed decreased plasma 17ß-estradiol. SIGNIFICANCE: Neonatal CS exposure induces changes in some biomarkers of the EC and DA systems, which can partially explain the hyperphagia observed in female rats.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Endocanabinoides/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Animais Recém-Nascidos , Fumar Cigarros , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/efeitos dos fármacos , Neurônios Dopaminérgicos/fisiologia , Endocanabinoides/fisiologia , Feminino , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Hipotálamo/metabolismo , Lactação/efeitos dos fármacos , Leptina/metabolismo , Lipase Lipoproteica/efeitos dos fármacos , Exposição Materna/efeitos adversos , Obesidade/etiologia , Obesidade/metabolismo , Ratos , Ratos Wistar , Receptores de Canabinoides/efeitos dos fármacos , Fumar , Tabaco
9.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151172

RESUMO

The adipocyte hormone leptin was first recognized for its actions in the central nervous system to regulate energy homeostasis but has since been shown to have direct actions on peripheral tissues. In pancreatic ß-cells leptin suppresses insulin secretion by increasing KATP channel conductance, which causes membrane hyperpolarization and renders ß-cells electrically silent. However, the mechanism by which leptin increases KATP channel conductance had remained unresolved for many years following the initial observation. Recent studies have revealed that leptin increases surface abundance of KATP channels by promoting channel trafficking to the ß-cell membrane. Thus, KATP channel trafficking regulation has emerged as a mechanism by which leptin increases KATP channel conductance to regulate ß-cell electrical activity and insulin secretion. This review will discuss the leptin signaling pathway that underlies KATP channel trafficking regulation in ß-cells.


Assuntos
Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Canais KATP/metabolismo , Leptina/metabolismo , Animais , Biomarcadores , Glucose/metabolismo , Humanos , Ligação Proteica , Transporte Proteico , Transdução de Sinais
10.
Biomed Res Int ; 2019: 2585743, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119158

RESUMO

Purpose: Leptin is a nutritional cytokine encoded by the obesity gene whose concentration in the tumor microenvironment is closely related to the occurrence and progression of cancer. However, previous evidence has suggested that there is no clear relationship between serum leptin concentrations and lung cancer progression. Cancer-associated fibroblasts (CAFs), the most abundant component of the tumor microenvironment in a variety of solid tumors, were recently reported to produce leptin. Therefore, it was inferred that leptin is most likely to affect non-small-cell lung cancer (NSCLC) through an autocrine and paracrine mechanism. In the current study, we investigated the paracrine effect and mechanism of leptin produced by CAFs on NSCLC by establishing a novel in vitro cell coculture system. Methods: A noncontact coculture device was designed and made by 3D printing. CAFs and paired normal lung fibroblasts (NLFs) from 5 patients were successfully isolated and cocultured with two NSCLC cell lines in a coculture system. The background expression of leptin was detected by western blot. The in situ expression of leptin and its receptor (Ob-R) in NSCLC tissues and paired normal lung tissues was analyzed by immunohistochemistry. Furthermore, we downregulated the expression of leptin in CAFs and assessed changes in its promotion on NSCLC cells in the coculture system. Finally, changes in the phosphorylation of ERK1/2 and AKT were examined to investigate the molecular mechanisms responsible for the paracrine promotion of NSCLC cells by leptin. Results: Leptin was overexpressed in nearly all five primary CAF lines compared with its expression in paired NLFs. IHC staining showed that the expression of leptin was high in NSCLC cells, slightly lower in CAF, and negative in normal lung tissue. Ob-R was strongly expressed in NSCLC cells. The ability of A549 and H1299 cells to proliferate and migrate was enhanced by high leptin levels in both the cocultured fibroblasts and the culture medium. Furthermore, western blot assays suggested that the MAPK/ERK1/2 and PI3K/AKT signaling pathways were activated by leptin produced by CAFs, which demonstrated that the functions of paracrine leptin in NSCLC are as those of the serum leptin to other cancers. Conclusion: Leptin produced by CAF promotes proliferation and migration of NSCLC cells probably via PI3K/AKT and MAPK/ERK1/2 signaling pathways in a paracrine manner.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/dietoterapia , Proliferação de Células/efeitos dos fármacos , Leptina/farmacologia , Comunicação Parácrina/efeitos dos fármacos , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Técnicas de Cocultura , Humanos , Leptina/genética , Leptina/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Comunicação Parácrina/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Microambiente Tumoral/efeitos dos fármacos
11.
Int J Mol Sci ; 20(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141984

RESUMO

Leptin, an adipocyte-derived hormone and its receptor (ObR) expressed in the hypothalamus are well known as an essential regulator of appetite and energy expenditure. Obesity induces abundant leptin production, however, reduced sensitivity to leptin leads to the development of metabolic disorders, so called leptin resistance. The stomach has been identified as an organ that simultaneously expresses leptin and ObR. Accumulating evidence has shown gastric leptin to perform diverse functions, such as those in nutrient absorption and carcinogenesis in the gastrointestinal system, independent of its well-known role in appetite regulation and obesity. Overexpression of leptin and phosphorylated ObR is implicated in gastric cancer in humans and in murine model, and diet-induced obesity causes precancerous lesions in the stomach in mice. While the underlying pathomechanisms remain unclear, leptin signaling can affect gastric mucosal milieu. In this review, we focus on the significant role of the gastric leptin signaling in neoplasia and tumorigenesis in stomach in the context of hereditary and diet-induced obesity.


Assuntos
Carcinogênese/metabolismo , Leptina/metabolismo , Obesidade/metabolismo , Neoplasias Gástricas/etiologia , Animais , Carcinogênese/genética , Humanos , Leptina/genética , Obesidade/complicações , Receptores para Leptina/genética , Receptores para Leptina/metabolismo
12.
Int J Mol Sci ; 20(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091785

RESUMO

Growing scientific evidence has unveiled increased incidences of obesity in domestic animals and its influence on a plethora of associated disorders. Leptin, an adipokine regulating body fat mass, represents a key molecule in obesity, able to modulate immune responses and foster chronic inflammatory response in peripheral tissues. High levels of cytokines and inflammatory markers suggest an association between inflammatory state and obesity in dogs, highlighting the parallelism with humans. Canine obesity is a relevant disease always accompanied with several health conditions such as inflammation, immune-dysregulation, insulin resistance, pancreatitis, orthopaedic disorders, cardiovascular disease, and neoplasia. However, leptin involvement in many disease processes in veterinary medicine is poorly understood. Moreover, hyperleptinemia as well as leptin resistance occur with cardiac dysfunction as a consequence of altered cardiac mitochondrial metabolism in obese dogs. Similarly, leptin dysregulation seems to be involved in the pancreatitis pathophysiology. This review aims to examine literature concerning leptin and immunological status in obese dogs, in particular for the aspects related to obesity-associated diseases.


Assuntos
Imunidade Adaptativa , Doenças do Cão/imunologia , Imunidade Inata , Leptina/genética , Obesidade/veterinária , Animais , Doenças do Cão/etiologia , Cães , Leptina/metabolismo , Obesidade/etiologia , Obesidade/imunologia
13.
Mol Cell Biochem ; 458(1-2): 207-217, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077012

RESUMO

Leptin induces ovarian cancer cell invasion via overexpression of MMP7, MMP9, and upA. In addition, the key role of ERα in leptin-increased cell growth was indicated. However, the influence of ER on leptin-mediated cell invasion remains still unknown. The present study was designed to evaluate the E2-independent effect of ERα/ß on leptin-mediated cell invasion and cell proliferation in ovarian cancer. We utilized SKOV3 cancer (expressing OB-Rb and ERα/ß, insensitive to estrogen) and OVCAR3 (expressing OB-Rb) cell lines to show the involvement of ER in leptin-mediated effects in an E2-independent manner. MTT, BrdU, and BD matrigel invasion assays were applied to analyze cell growth, proliferation, and invasion. The siRNA approach was used to confirm the role of ERα/ß in leptin effects. Moreover, western blotting and Real-time PCR were employed to detect the OB-Rb, ER, MMP9/7, and upA proteins and mRNAs. Leptin, in the absence of E2, increased ERα expression in SKOV3 cells, which was attenuated using knockdown of OB-Rb gene by siRNA. The effect of leptin on the cell growth was promoted in the presence of PPT, but not in the presence of DNP and E2, which was lost when OB-Rb siRNA was transfected. Furthermore, ERα gene silencing and/or pre-incubation with ER antagonist (ICI 182,780, 10 nM) significantly reduced cell invasion and MMP9 expression stimulated by leptin. In conclusion, our findings demonstrated that ERα, but not ERß, is involved in leptin-induced ovarian cancer in an E2-independent manner, providing new evidence for cancer progression in obesity-associated ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Receptor alfa de Estrogênio/metabolismo , Leptina/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Receptores para Leptina/metabolismo , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Leptina/genética , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores para Leptina/genética
14.
Int J Mol Med ; 44(1): 301-312, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115489

RESUMO

Transplantation of mesenchymal stem cells (MSCs) is emerging as a potential therapy for cardiovascular diseases. However, the poor survival of transplanted MSCs is a major obstacle to improving their clinical efficacy. Accumulating evidence indicates that hypoxic preconditioning (HPC) can improve the survival of MSCs. It has been previously reported that leptin plays a critical role in HPC­enhanced MSC survival through increasing optic atrophy 1 (OPA1)­dependent mitochondrial fusion. Survival of MSCs mainly relies on glycolysis as an energy source. The close relationship between leptin and glucose homeostasis has attracted intense scientific interest. Furthermore, emerging evidence indicates that mitochondrial dynamics (fusion and fission) are associated with alterations in glycolysis. The aim of the present study was to investigate whether leptin increases MSC survival through metabolic regulation. Leptin­modulated increased OPA1 expression was found to be associated with increased glycolysis. However, the glycolytic efficacy of leptin was abrogated after silencing OPA1 using a selective siRNA, suggesting that OPA1 directly regulates glycolysis. Furthermore, the activation of sodium­glucose symporter 1 (SGLT1) was markedly induced by leptin. However, leptin­induced glycolysis was primarily blocked by SGLT1 inhibitor treatment. Thus, leptin regulates OPA1­dependent glycolysis to improve MSC survival primarily through SGLT1 activation. We therefore identified a pivotal leptin/OPA1/SGLT1 signaling pathway for mitochondrial dynamic­mediated glycolysis, which may optimize the therapeutic efficiency of MSCs.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Glicólise , Leptina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Dinâmica Mitocondrial , Transdução de Sinais , Sobrevivência Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/patologia , Transportador 1 de Glucose-Sódio/metabolismo
15.
Horm Metab Res ; 51(5): 330-335, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30943548

RESUMO

The goal of this study is to investigate whether congenital hypothyroidism induced by MMI during gestation (G) or gestation plus lactation (GL) would affect the leptin action upon body weight control on hypothalamus. Six to eight pups per group were killed at 90 days of age. For statistical analysis one-way ANOVA followed by the Holm-Sìdak post hoc test was used. Hypothyroidism resulted in a significant increase in leptin serum levels in G 20% and GL 25% (p<0.04). There was a significant expression decrease of OBR in G 45% and GL 63%; pSTAT3 in G 56% and GL 51%; pERK in G 50% and GL 48%; POMC in G 41% and GL 46% (p<0.04), while a significant increase was assigned to SOCS3 in G 52% and GL 170% (p<0.04) protein expression. We can conclude that hypothyroxinemia condition in rats on adulthood results in impairment of the leptin signaling pathway via ObRb-STAT3 in the hypothalamus, which is likely to be involved in the leptin resistance.


Assuntos
Envelhecimento/metabolismo , Hipotireoidismo Congênito/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Transdução de Sinais , Animais , Peso Corporal , Hipotireoidismo Congênito/sangue , Comportamento Alimentar , Feminino , Hormônios/sangue , Leptina/sangue , Masculino , Ratos Wistar
16.
Nutrients ; 11(4)2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935076

RESUMO

The gastrointestinal-brain axis is a key mediator of the body weight and energy homeostasis regulation. Uroguanylin (UGN) has been recently proposed to be a part of this gut-brain axis regulating food intake, body weight and energy expenditure. Expression of UGN is regulated by the nutritional status and dependent on leptin levels. However, the exact molecular mechanisms underlying this UGN-leptin metabolic regulation at a hypothalamic level still remains unclear. Using leptin resistant diet-induced obese (DIO) mice, we aimed to determine whether UGN could improve hypothalamic leptin sensitivity. The present work demonstrates that the central co-administration of UGN and leptin potentiates leptin's ability to decrease the food intake and body weight in DIO mice, and that UGN activates the hypothalamic signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositide 3-kinases (PI3K) pathways. At a functional level, the blockade of PI3K, but not STAT3, blunted UGN-mediated leptin responsiveness in DIO mice. Overall, these findings indicate that UGN improves leptin sensitivity in DIO mice.


Assuntos
Ingestão de Alimentos/efeitos dos fármacos , Leptina/metabolismo , Peptídeos Natriuréticos/metabolismo , Obesidade/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Dieta/efeitos adversos , Hipotálamo/metabolismo , Camundongos , Camundongos Obesos , Obesidade/etiologia , Fosfatidilinositol 3-Quinase/metabolismo , Fator de Transcrição STAT3/metabolismo
17.
J Med Food ; 22(6): 560-566, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31013456

RESUMO

The gut microbiota is the most important environmental factor that plays a role in inducing obesity. The gram-negative bacteria, Enterobacter cloacae strains, recently identified in obese mice are considered to be pathogenic bacteria in the gut. Probiotics are important members of the gut microbiota and exert beneficial effects, including inhibiting the growth of potential pathogenic bacteria. Therefore, we isolated a total of 230 lactic acid bacteria from traditional, Korean fermented foods and fecal samples from newborn infants, including Lactobacillus plantarum LMT1-48, which exhibited maximal antimicrobial activity against E. cloacae. We next investigated the functional antiobesity effects of L. plantarum LMT1-48 in an E. cloacae-induced high-fat diet (HFD)-fed animal obesity model. To this end, the L. plantarum LMT1-48 showed antiobesity effects, including body weight loss and reduction of abdominal fat volume, which was accompanied by a decrease in leptin and total cholesterol levels in E. cloacae-induced HFD-fed mice. Notably, gut microbiota diversity also increased after long-term ingestion of L. plantarum LMT1-48, resulting in amelioration of obesity in E. cloacae-induced HFD-fed mice. Accordingly, results suggest that dietary intake of L. plantarum LMT1-48 protects against the onset of E. cloacae-induced obesity.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Enterobacter cloacae/fisiologia , Lactobacillus plantarum/fisiologia , Obesidade/tratamento farmacológico , Probióticos/administração & dosagem , Animais , Antibiose , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Humanos , Intestinos/microbiologia , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Obesidade/microbiologia , Triglicerídeos/metabolismo
18.
Nat Commun ; 10(1): 1718, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979869

RESUMO

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.


Assuntos
Hipotálamo/metabolismo , Neurônios/metabolismo , Coativador 1 de Receptor Nuclear/genética , Coativador 1 de Receptor Nuclear/metabolismo , Obesidade/genética , Alelos , Animais , Peso Corporal , Linhagem Celular Tumoral , Cruzamentos Genéticos , Deleção de Genes , Técnicas de Introdução de Genes , Variação Genética , Células HEK293 , Heterozigoto , Homeostase , Humanos , Leptina/metabolismo , Masculino , Potenciais da Membrana , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto , Obesidade/metabolismo , Fenótipo
19.
Nutrients ; 11(2)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813240

RESUMO

Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ≥1.0 can be considered normal, a ratio of ≥0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = -0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Leptina/metabolismo , Obesidade/metabolismo , Tecido Adiposo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos Transversais , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Mater Sci Eng C Mater Biol Appl ; 99: 1257-1273, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889661

RESUMO

Lithium (Li+) ion due to its excellent bioactivity is one of the most well-studied element in bone-tissue engineering. In this study, we fabricated nanohydroxyapatite (nHAp) doped with Li+ ions (5 mol% Li+:nHAp) and co-doped with lanthanide ions. We investigated the effects of nHAp, 5 mol% Li+:nHAp or Li+ alone, on osteogenic differentiation of human Adipose Tissue-derived Stem Cells (hASCs), their proliferation, mitochondrial dynamics and apoptosis. Moreover, we monitored cell proliferation after treatment with samarium (III) (Sm3+) and europium (III) (Eu3+) ions co-doped 5 mol% Li+:nHAp as well as their luminescent property. The hASCs treated with 5 mol% Li+:nHAp and Li+ ions proliferated more rapidly and differentiated effectively than control cells without undergoing apoptosis. Both, 5 mol% Li+:nHAp and Li+ ions improved osteogenic differentiation of hASCs. Moreover they decreased expression of glycogen synthase kinase 3ß (GSK3ß) while increased ß-catenin mRNA level. In addition, Li+, nHAp and 5 mol% Li+:nHAp improved mitochondrial dynamics and enhanced expression of neural differentiation marker genes. Collectively, the study indicates on pro-osteogenic and anti-apoptotic properties of nHAp doped with Li+ and Li+ alone. Moreover, unique properties of 5 mol% Li+:nHAp and 5 mol% Li+:nHAp co-doped with rare earth ions, such as Sm3+ and Eu3+ have shed a promising light on their potential application in theranostics.


Assuntos
Durapatita/química , Európio/farmacologia , Lítio/farmacologia , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Samário/farmacologia , Nanomedicina Teranóstica , Apoptose , Biomarcadores/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Humanos , Íons , Leptina/genética , Leptina/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Nanopartículas/ultraestrutura , Nestina/genética , Nestina/metabolismo , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Osteogênese/genética , Osteopontina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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