RESUMO
PURPOSE: This study examines whether G-protein coupled receptor 120 (GPR120) is involved in the pro-/anti-inflammatory effects of different types of fatty acids (FAs) in human visceral adipocytes, and whether these effects may be altered in obesity, a state with a chronic inflammation. METHODS: Pro-/anti-inflammatory effects of palmitic, oleic, linoleic and docosahexaenoic acids on human visceral adipocytes were tested in mature adipocytes from non-obese and morbidly obese (MO) subjects. Also, the effects of these FAs were tested when the GPR120 gene was silenced. RESULTS: In adipocytes from non-obese subjects, palmitic and linoleic acids increased TNF-α and IL-6 mRNA expression (p < 0.05), and decreased IL-10 and adiponectin expression (p < 0.05). However, oleic and docosahexaenoic acids (DHA) produced the opposite effect (p < 0.05). In adipocytes from MO subjects, all FAs used increased TNF-α and IL-6 expression (p < 0.05). Palmitic and linoleic acids decreased IL-10 and adiponectin expression (p < 0.05), but oleic acid and DHA did not have significant effects. Only oleic acid increased adiponectin expression (p < 0.05). The effects of FAs on TNF-α, IL-6, IL-10 and adiponectin expression in non-obese and MO subjects were significantly annulled when the GPR120 gene was silenced in visceral adipocytes differentiated from human mesenchymal stem cells. CONCLUSIONS: FAs are capable of directly acting on visceral adipocytes to modulate differently TNF-α, IL-6, IL-10 and adiponectin expression, with a different and greater effect in MO subjects. These effects are largely annulled when GPR120 expression was silenced, which suggests that they could be mediated by GPR120.
Assuntos
Adipócitos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Ácidos Graxos/farmacologia , Inflamação/tratamento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Adulto , Índice de Massa Corporal , Peso Corporal , Colesterol/sangue , Doença Crônica , Feminino , Inativação Gênica , Humanos , Insulina/sangue , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: Irisin activates the thermogenic function in adipose tissues. However, little is known on the association between human irisin and different cardiometabolic risk factors. We analyse the influence of morbid obesity on irisin levels and its relation with leptin and different cardiovascular risk factors. MATERIAL AND METHODS: We measured the serum irisin level and the fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue from 33 morbidly obese subjects and 12 nonobese subjects. We also studied the effect of leptin on FNDC5 expression. RESULTS: Serum irisin was higher in the nonobese subjects than in morbidly obese subjects, both before (P = 0·043) and after bariatric surgery (P = 0·042). The variable that best explained the serum irisin levels in a multiple linear regression model was the waist-to-hip ratio (WHR) (R(2) = 0·201) (Beta = -0·357, P = 0·046). Those morbidly obese subjects with android-type obesity had lower serum irisin levels than those with gynecoid-type obesity, both before (P = 0·027) and after bariatric surgery (P = 0·006). Only the percentage change in WHR was associated with serum irisin levels after bariatric surgery (r = -0·529, P = 0·005). FNDC5 expression levels in subcutaneous adipose tissue (SAT) were higher in the nonobese than in the morbidly obese subjects (P = 0·042). In SAT explants from nonobese subjects, leptin (20 and 150 ng/mL) produced a decrease in FNDC5 expression (P = 0·009 and P = 0·037, respectively). CONCLUSIONS: We showed decreased serum irisin levels in morbidly obese subjects, related mainly to WHR. FNDC5 expression could be regulated by leptin.
Assuntos
Fibronectinas/metabolismo , Gordura Intra-Abdominal/química , Leptina/fisiologia , Obesidade Mórbida/sangue , Gordura Subcutânea/química , Adulto , Regulação para Baixo , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Humanos , Masculino , RNA Mensageiro/metabolismo , Relação Cintura-QuadrilRESUMO
SCOPE: The effects that fatty acids (FAs) exert on G protein-coupled receptor-120 (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the association between GPR120 and obesity, and the FA effects on its expression. METHODS AND RESULTS: GPR120 levels were analyzed in visceral adipose tissue (VAT) from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a high-fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in the fasting state was lower in morbidly obese subjects (p = 0.04), with a decrease 3 h after a high-fat meal only in morbidly obese subjects (p = 0.043). Also, incubations of visceral adipocytes from these subjects were made with different FAs. In nonobese subjects, palmitic, oleic, linoleic, and docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p < 0.05). In morbidly obese subjects, only linoleic acid produced an increase in GPR120 mRNA and protein levels (p < 0.05). CONCLUSION: Morbidly obese subjects had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after a high-fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120 mRNA and protein levels in visceral adipocytes was lower in morbidly obese subjects.