Endocrine Abstracts

Obesity is linked to common metabolic diseases including insulin resistance, which constitutes a principal risk factor for type 2 diabetes. Increasing evidence indicates that changes in adipose-secreted factors in obesity, dramatically affect insulin sensitivity. Among these adipokines, resistin is described as a key factor in obesity-mediated both inflammation and insulin resistance. However, little is known about the molecular mechanisms mediating resistin effects particular...

FGF21 has recently emerged as a major regulator of metabolism and energy utilisation. FGF21 administration confers multiple metabolic benefits on insulin sensitivity, blood glucose, lipid profile and body weight in rodents and primates. FGF21 acts through a receptor complex consisting of FGF receptors (FGFR 1, 2, 3 or 4) and a co-receptor βKlotho (KLB), crucially required for FGF21 signaling. Although FGFRs are widely expressed, KLB is predominantly expressed in adipose t...

Toll-like receptor 4 (TLR4) has a critical role in innate immunity, and the activation of inflammatory pathways plays an important role in the induction of insulin resistance. Indeed, we have recently demonstrated that TLR4 is implicated in resistin-induced inflammation and insulin resistance in the hypothalamus.1 We have also shown that TLR4 is up-regulated in the hypothalamus of mice fed a high-fat diet. Here, we aim to decipher the molecular mechanisms implicated...

Resistin promotes both inflammation and insulin resistance associated with energy homeostasis impairment. Resistin is secreted by adipose tissue and macrophages, but its mechanism of action remained unknown because its receptor was not characterised. Recently, we have shown that central resistin acts by way of hypothalamic TLR4 receptors promoting overall inflammation and insulin resistance. Here, we aim to block resistin action in HFD mice that are prone to obesity and inflam...

Obesity and its major consequence, type II diabetes mellitus (T2DM), is epidemic throughout Western society. T2DM accounts for 95% of the diabetes worldwide. One limitation to the development of new diabetes treatments has been a lack of effective animal models to use in research. There are no rodent models that recapitulate the pancreatic β-cell lesions of humans with T2DM. Moreover, animal models of obesity either require overfeeding which is expensive and takes weeks t...

Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in variety of biological processes including energy metabolism, reproduction and modulation of the immune response. So far structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high-affinity mutants by yeast-surface display and discovered that replacing residue D23 with a non-negatively charged amino a...

Recent reports have revealed that leptin’s effects are not restricted to central control of body weight, demonstrating instead that leptin is a pleiotropic hormone with a wide variety of different biological actions. Leptin exhibits undesirable effects in autoimmune diseases, in atherosclerosis, and possibly in several types of cancer, and increases the risk of cardiovascular disease in obese people. Therefore, preparation of reagents capable of abolishing leptin’s a...