Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

Obesity, inflammation, and insulin resistance

White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT

Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis

© 2011 Elsevier Inc

Interleukin-6 Signaling in Liver-Parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action

The contribution of interleukin (IL)-6 signaling in obesity-induced inflammation remains controversial. To specifically define the role of hepatic IL-6 signaling in insulin action and resistance, we have generated mice with hepatocyte-specific IL-6 receptor (IL-6R) a deficiency (IL-6RaL-KO mice). These animals showed no alterations in body weight and fat content but exhibited a reduction in insulin sensitivity and glucose tolerance. Impaired glucose metabolism originated from attenuated insulin-stimulated glucose transport in skeletal muscle and fat. Surprisingly, hepatic IL-6Ra-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-a, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of IkBa. Neutralization of TNF-a or ablation of Kupffer cells restored glucose tolerance in IL-6RaL-KO mice. Thus, our results reveal an unexpected role for hepatic IL-6 signaling to limit hepatic inflammation and to protect from local and systemic insulin resistance