THE CONCEPT OF LEPTIN RESISTANCE appeared in the literature almost as soon as the hormone itself was discovered. For purposes of our discussion, leptin resistance will be defined as, “reduced or absent responsiveness to the feeding and body weight inhibitory effects of the hormone in obese individuals in comparison with normal (lean) controls.” Two early reports, demonstrating significant corre...

Neuropeptide Y (NPY) neurons in both the arcuate nucleus of the hypothalamus (ARH) and the dorsomedial hypothalamus (DMH) have been implicated in food intake and obesity. However, while ARH NPY is highly expressed in the lean animal, DMH NPY mRNA expression is observed only after diet-induced obesity (DIO). Furthermore, while ARH NPY neurons are inhibited by leptin, the effect of this adipokine...

OBJECTIVE The dorsomedial hypothalamus (DMH) has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), leptin receptor, and melanocor...

Siberian hamsters decreased body weight by 30% during 18 wk in short day (SD) vs. long day (LD) controls. Subsequent imposed food deprivation (FD; 24 h) caused a further 10% decrease. In the hypothalamic arcuate nucleus (ARC), SDs reduced proopiomelanocortin (POMC) gene expression and agouti-related protein (AGRP) mRNA was elevated, changes that summate to reduced catabolic drive through the me...

OBJECTIVE There is increasing evidence of an association between leptin and increased cardiovascular risk. Higher leptin levels are associated with increased levels of C-reactive protein (CRP), which itself elicits proatherogenic effects in the vascular endothelium. We tested the hypothesis that leptin induces CRP expression in human coronary artery endothelial cells (HCAECs). METHODS AND RES...

BACKGROUND Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear. METHODS AND RESULTS Arterial injury was induced in wild-type (wt), leptin-deficient (lep(ob/ob)), and leptin receptor-deficient (lep...

Monocytes/macrophages are key mediators of wound repair, tissue remodeling, and inflammation. However, the molecular mechanisms underlying macrophage recruitment to the site of inflammation is not fully understood. Leptin acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. The leptin receptor, a single transmembrane protein that belongs to the gp130 family ...

Leptin, the product of the ob gene, is a pleiotropic molecule that regulates food intake as well as metabolic and endocrine functions. Leptin also plays a regulatory role in immunity, inflammation, and hematopoiesis. Alterations in immune and inflammatory responses are present in leptin- or leptin-receptor-deficient animals, as well as during starvation and malnutrition, two conditions characte...