RESUMO
BACKGROUND: Growth hormone-releasing hormone (GHRH) has a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism. OBJECTIVES: To determine whether GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analyze the effects of GHRH on human adipocyte differentiation and lipolysis. METHODS: GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects. Human mesenchymal stem cells (HMSC) were differentiated to adipocytes with GHRH (10-14-10-8 M). Adipocyte differentiation, lipolysis and gene expression were measured and the effect of GH-R silencing was determined. RESULTS: Mature adipocytes from morbidly obese subjects showed a higher expression of GHRH and GH-R, and a lower expression of GHRH-R and GH than non-obese subjects (P<0.05). A total of 10-14-10-10 M GHRH induced an inhibition of lipid accumulation and PPAR-γ expression (P<0.05), and an increase in glycerol release and HSL expression (P<0.05) in human differentiated adipocytes. A total of 10-12-10-8 M GHRH decreased GHRH-R expression in human differentiated adipocytes (P<0.05). A total of 10-10-10-8 M GHRH increased GH and GH-R expression in human differentiated adipocytes (P<0.05). The effects of GHRH at 10-10 M on adipocyte differentiation and lipolysis were blocked when GH-R expression was silenced. CONCLUSIONS: GHRH and GHRH-R are expressed in human adipocytes and are negatively associated. GHRH at low doses may exert an anti-obesity effect by inhibiting HMSC differentiation in adipocytes and by increasing adipocyte lipolysis in an autocrine or paracrine pathway. These effects are mediated by GH and GH-R.
Assuntos
Adipócitos/citologia , Adipócitos/metabolismo , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Lipólise , Receptores da Somatotropina/metabolismo , Adipogenia , Adulto , Diferenciação Celular , Feminino , Inativação Gênica , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/biossíntese , Humanos , Masculino , Obesidade Mórbida/genética , PPAR gama/metabolismo , Receptores de Neuropeptídeos/metabolismo , Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismoRESUMO
Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Biomarcadores/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r = -0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Jejuno/metabolismo , Obesidade Mórbida/metabolismo , Triglicerídeos/metabolismo , Apolipoproteína B-48/sangue , Apolipoproteína B-48/metabolismo , Apolipoproteínas A/sangue , Apolipoproteínas A/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Resistência à Insulina , Jejuno/patologia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Triglicerídeos/sangueRESUMO
BACKGROUND AND AIMS: As interleukin-6 (IL-6) has an important role in general metabolism with high circulating levels in obesity and other associated diseases, the factors regulating its synthesis and release have been considered possible therapeutic targets and have recently been studied. We examined the influence of three different diets, each having a different fatty acid composition--saturated, monounsaturated or polyunsaturated (coconut oil, olive oil and sunflower oil diets), on IL-6 release from rat adipocytes, and the interaction between diet and other regulatory factors of IL-6 release, such as epinephrine. METHODS: A group of rats was assigned to one of the three different diets, each with a significantly different concentration of saturated, monounsaturated and polyunsaturated fatty acids. Samples were taken from the omental adipose tissue for measurement of the triacylglycerol fatty acid composition of the tissues and for adipocyte isolation. IL-6 release from adipocytes was measured in vitro, under nonstimulated conditions and also with two concentrations of epinephrine in the medium. RESULTS: Animals fed with the olive oil diet showed lower values of IL-6 release with and without epinephrine stimulation. IL-6 release from adipocytes varied according to the diet, but not according to epinephrine dose. However, a significant interaction was found between the epinephrine dose and the diet in IL-6 release regulation. CONCLUSIONS: IL-6 release from adipocytes was markedly regulated by the dietary fatty acid composition, even under epinephrine stimulation, with lower values of IL-6 release in the olive oil diet. The study also showed that epinephrine regulation of IL-6 release was related to the diet.
Assuntos
Adipócitos/efeitos dos fármacos , Epinefrina/farmacologia , Interleucina-6/metabolismo , Óleos de Plantas/farmacologia , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Óleo de Coco , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Masculino , Azeite de Oliva , Ratos , Ratos Sprague-Dawley , Óleo de GirassolRESUMO
Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.
Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Obesidade/epidemiologia , Adulto , Idoso , Glicemia , Pressão Sanguínea , Peso Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Fatores de Risco , Espanha/epidemiologiaRESUMO
OBJECTIVE: Changes in eating habits may be influential in the ever-increasing rate of childhood obesity. Our aim was to determine whether those children who consume olive oil have a lower risk of weight gain compared with children who consume other oils. DESIGN AND METHODS: The study included 18 girls and 74 boys, all aged 13-166 months. A survey was completed for each subject about eating habits and physical activity. A sample of subcutaneous adipose tissue was also obtained for cellular study. Data were recorded on the mean size of the adipocytes, the number of preadipocytes, and the concentration of particular fatty acids. The weight and height of the children were measured 13 months later. RESULTS: The likelihood that after 1 year the children would have increased their body mass index (BMI) Z-score above the initial score was less in the children who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI): 0.08-0.63; P=0.005). These results remained after adjusting for age, physical activity and BMI (OR=0.19; 95% CI: 0.06-0.61; P=0.005) and after adjusting for age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04-0.52; P=0.003). CONCLUSIONS: Diets with mono unsaturated fatty acid (MUFA)-rich olive oil could reduce the risk of obesity in childhood.