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The neuronal circuits involved in the regulation of feeding behavior and energy expenditure are soft-wired, reflecting the relative activity of the postsynaptic neuronal system, including the anorexigenic proopiomelanocortin (POMC)-expressing cells of the arcuate nucleus. We analyzed the synaptic input organization of the melanocortin system in lean rats(More)
Current evidence suggests that hypothalamic fatty acid metabolism may play a role in regulating food intake; however, confirmation that it is a physiologically relevant regulatory system of feeding is still incomplete. Here, we use pharmacological and genetic approaches to demonstrate that the physiological orexigenic response to ghrelin involves specific(More)
Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its(More)
We report the efficacy of a new peptide with agonism at the glucagon and GLP-1 receptors that has potent, sustained satiation-inducing and lipolytic effects. Selective chemical modification to glucagon resulted in a loss of specificity, with minimal change to inherent activity. The structural basis for the co-agonism appears to be a combination of local(More)
Entrainment of anticipatory activity and wakefulness to nutrient availability is a poorly understood component of energy homeostasis. Restricted feeding (RF) paradigms with a periodicity of 24 h rapidly induce entrainment of rhythms anticipating food presentation that are independent of master clocks in the suprachiasmatic nucleus (SCN) but do require other(More)
Existing monotherapies for the treatment of obesity provide only modest weight loss and/or have adverse side effects, and this is also the case with the cannabinoid receptor 1 (CB1) inverse agonist, rimonabant. We aimed to investigate the possibility of improving efficacy and reducing side effects of rimonabant by cotreatment with opioid system antagonists.(More)
Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol(More)
Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and(More)
Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the CNS. The CNS also directly regulates adipocyte metabolism, as we have shown here by examining central action of the orexigenic hormone ghrelin. Chronic central ghrelin infusion resulted in increases in the glucose utilization rate of white(More)
Glucagon has long been known as a counter-regulatory hormone to insulin of fundamental importance to glucose homeostasis. Its prominent ability to stimulate glycogenolysis and gluconeogenesis, has historically cast this peptide as one hormone where the metabolic consequences of increasing blood glucose levels, especially in obesity, are viewed largely as(More)