RESUMO
Background: About 30% of patients treated with second generation antipsychotics (SGA) experience weight gain. Although there is evidence that the FTO gene is associated with obesity its role in antipsychotic induced weight gain is not so clear. Methods: A genetic association study was carried out to identify the association between FTO rs9939609 and antipsychotic induced weight gain. Sample consisted of 180 cases and 120 controls. Cases were patients diagnosed with schizophrenia or schizoaffective disorder, treated with second-generation antipsychotics for a minimum of 3 months, and had gained at least 10% of body weight. Controls were patients with schizophrenia treated with second-generation antipsychotics for a minimum of 3 months but had not gained ≥10% of body weight. Genomic DNA was extracted from whole blood. Polymerase chain reaction of the samples was done. Real-time quantitative PCR (qPCR) was carried out using BIO-RAD CFX96 Touch TM PCR detection system. Results: Females were significantly more among cases (58.3%) than controls (35%). Cases (52.4%) were significantly more likely to be overweight or obese than controls (13.8%). Genotype distribution was in Hardy-Weinberg equilibrium (p=0.43). Cochran-Armitage trend test was not significant. Risk of antipsychotic induced weight gain in the AA genotype [OR 1.69 (95% CI 0.74-3.86)] and AT genotype [OR 1.1 (95% CI 0.67-1.79)] were not significantly higher than the TT genotype. Recessive model showed that AA/AT genotypes were at significantly higher risk of being obese/overweight [OR 1.84 (95% CI 1.05-3.2)]. Conclusions: There was no significant association between FTO rs9939609 and antipsychotic induced weight gain. AA/AT genotypes had significantly higher risk of overweight/obesity.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Sobrepeso/genética , Esquizofrenia/tratamento farmacológico , Aumento de Peso/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Obesidade/genética , Sobrepeso/induzido quimicamente , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Esquizofrenia/genética , Sri LankaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Peçonhas/farmacologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Cromonas/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Exenatida , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas In Vitro , Insulina/sangue , Masculino , Malondialdeído/análise , Morfolinas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Coelhos , Superóxido Dismutase/análiseRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.
