Teubner BJ, Keen-Rhinehart E, Bartness TJ. Third ventricular coinjection of subthreshold doses of NPY and AgRP stimulate food hoarding and intake and neural activation. Am J Physiol Regul Integr Comp Physiol 302: R37–R48, 2012. First published October 19, 2011; doi:10.1152/ajpregu.00475.2011.—We previously demonstrated that 3rd ventricular (3V) neuropeptide Y (NPY) or agouti-related protein (Ag...

Although excess hypothalamic agouti-related peptide (AGRP), an endogenous antagonist of the melanocortin 3/4 receptor, causes hyperphagia and obesity, its role in regulating cardiovascular function is unclear. This study examined control of mean arterial pressure (MAP), heart rate (HR), and metabolism during chronic central administration of AGRP in rats. A cannula was placed in the lateral ven...

The central melanocortin (MC) system has been demonstrated to act downstream of leptin in the regulation of body weight. The system comprises alpha-MSH, which acts as agonist, and agouti-related protein (AgRP), which acts as antagonist at the MC3 and MC4 receptors (MC3R and MC4R). This property suggests that MCR activity is tightly regulated and that opposing signals are integrated at the recep...

The melanocortin 4 receptor (MC4R) is a G-protein coupled receptor mainly expressed in the central nervous system of vertebrates. Activation of the MC4R leads to a decrease in food intake, while inactivating mutations are a genetic cause of obesity. The binding of agoutirelated protein (AGRP) reduces agonist-stimulated cAMP production (competitive antagonist) but also the basal activity of the ...

In the present study we examined the diurnal patterns of agouti-related protein (AGRP) and proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus and their relation to circulating glucocorticoids and food intake. Animals were killed at 4-h intervals throughout the 24-h diurnal cycle, and the expression of AGRP and POMC mRNA was evaluated by semiquantitative in situ hybridization anal...

In many mammals, body weight increases continuously throughout adulthood until late middle age. The hormone leptin is necessary for maintaining body weight, in that high levels of leptin promote negative energy balance. As animals age, however, their increase in body weight is accompanied by a steady rise in circulating leptin levels, indicating the progressive development of counterregulatory ...

Nociceptin or orphanin FQ (N/OFQ) and its receptor NOP1 are expressed in hypothalamic nuclei involved in energy homeostasis. N/OFQ administered by intracerebroventricular or arcuate nucleus (ARC) injection increases food intake in satiated rats. The mechanisms by which N/OFQ increases food intake are unknown. We hypothesized that N/OFQ may regulate hypothalamic neurons containing peptides invol...

Aberrant melanocortin signaling has been implicated in the pathogenesis of wasting in chronic kidney disease (CKD). Previously, we demonstrated that agouti-related peptide (AgRP), a melenocortin-4 receptor antagonist, reduced CKD-associated cachexia in CKD mice. Our previous studies with AgRP utilized dual energy X-ray (DXA) densitometry to assess the body composition in mice (Cheung W, Kuo HJ,...

Neuropeptide Y (NPY) and agouti gene-related protein (AGRP) are orexigenic peptides of special importance for control of food intake. In situ hybridization studies have shown that NPY and AGRP mRNAs are increased in the arcuate nucleus of the hypothalamus (ARC) by glucoprivation. Other work has shown that glucoprivation stimulates food intake by activation of hindbrain glucoreceptor cells and r...

Insulin and leptin intracellular signaling pathways converge and act synergistically on the hypothalamic phosphatidylinositol-3-OH kinase/3-phosphoinositide-dependent protein kinase 1 (PDK1). However, little is known about whether PDK1 in agouti-related peptide (AGRP) neurons contributes to energy homeostasis. We generated AGRP neuron-specific PDK1 knockout (AGRPPdk1(-/-)) mice and mice with se...