AMP-activated protein kinase (AMPK) acts as a cellular energy sensor, being activated during states of low energy charge. Hypothalamic AMPK activity is altered by hormonal and metabolic signals and mediates the feeding response. To determine the effect of diabetes on hypothalamic AMPK activity, we assayed this activity in streptozotocin (STZ)-induced diabetic rats. Compared with control rats, S...

Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY; 10 micrograms/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver and adipose tissue lipogenic activity. It also increased basal morning corticosteronemia. When NPY-induced hyperp...

Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in triglyceride synthesis, have increased energy expenditure and therefore are resistant to obesity. Because ambient temperature can significantly affect energy expenditure in mice, we undertook these studies to determine the effects of different ambient temperatures on energy expenditure, food intake, and thermoregula...

The dramatic increase in the prevalence of obesity reflects a lack of progress in combating one of the most serious health problems of this century. Recent studies have improved our understanding of the appetitive network by focusing on the paraventricular hypothalamus (PVH), a key region responsible for the homeostatic balance of food intake. Here we show that mice with PVH-specific ablation o...

Ghrelin, a circulating growth hormone-releasing peptide derived from the stomach, stimulates food intake. The lowest systemically effective orexigenic dose of ghrelin was investigated and the resulting plasma ghrelin concentration was compared with that during fasting. The lowest dose of ghrelin that produced a significant stimulation of feeding after intraperitoneal injection was 1 nmol. The p...

The melanocortin receptor 4 (MC4R) is a well-established mediator of body weight homeostasis. However, the neurotransmitter(s) that mediate MC4R function remain largely unknown; as a result, little is known about the second-order neurons of the MC4R neural pathway. Single-minded 1 (Sim1)-expressing brain regions, which include the paraventricular nucleus of hypothalamus (PVH), represent key bra...

The neurosteroid allopregnanolone may increase feeding by altering food palatability; however, it may also increase feeding by reducing anxiety (neophobia). Moreover, it is unclear whether this induced hyperphagia is selective to safe, palatable foods only. Male rats were injected with allopregnanolone 20 min prior to behavioral testing. The taste reactivity test was used to examine possible sh...

Transgenic expression in the hypothalamus of syndecan-1, a cell surface heparan sulfate proteoglycan (HSPG) and modulator of ligand-receptor encounters, produces mice with hyperphagia and maturity-onset obesity resembling mice with reduced action of alpha melanocyte stimulating hormone (alphaMSH). Via their HS chains, syndecans potentiate the action of agouti-related protein and agouti signalin...