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Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status. We investigated the potential role of AMPK in the hypothalamus in the(More)
Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5'-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length(More)
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(More)
Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates the oxidation of fatty acids and the uptake of glucose, and prevents the accumulation of lipids in nonadipose tissues, which can lead to functional impairments known as "lipotoxicity". The(More)
Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP))(More)
Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in(More)
Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by(More)
A single bout of exercise increases expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1alpha expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic(More)
We studied the effects of microinjection of leptin into the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) on glucose uptake in peripheral tissues in unanesthetized rats. The rate of glucose uptake was assessed in vivo by 2-[3H]deoxyglucose incorporation. Single injection of leptin into VMH increased glucose uptake in brown adipose tissue(More)
Our previous study demonstrated that microinjection of leptin into the ventromedial hypothalamus (VMH) dramatically increased glucose uptake in the heart, brown adipose tissue (BAT), and skeletal muscles, but not in white adipose tissue (WAT) in conscious unrestrained rats, as assessed in vivo by the 2-[3H]deoxyglucose method. Here we examined the role of(More)