RESUMO
Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.
Assuntos
Adiponectina/fisiologia , Ingestão de Alimentos , Hipotálamo/enzimologia , Complexos Multienzimáticos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases Ativadas por AMP , Adenoviridae/genética , Adiponectina/líquido cefalorraquidiano , Adiponectina/genética , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Metabolismo Energético , Feminino , Hipotálamo/patologia , Técnicas Imunoenzimáticas , Hibridização In Situ , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complexos Multienzimáticos/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Sondas RNA , Receptores de Adiponectina , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores para LeptinaRESUMO
Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM.