Regulation of obesity and insulin resistance by nitric oxide

Abstract

Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a world-wide pandemic with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many “distal” causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity—those that directly regulate energy metabolism or caloric intake—appear to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease.

Evidence for elevated (LIMK2 and CFL1) and suppressed (ICAM1, EZR, MAP2K2, and NOS3) gene expressions in metabolic syndrome

“…Lower NOS3 abundance is found in both adipose tissue and skeletal muscle of obese humans [30,31]. Decreased NOS3 expression commonly occurs in obese and diabetic states [32]. Beyond changes in expression, the NO-producing activity of NOS3 is diminished in metabolic disease [32].…”

Effect of Transdermal Nitroglycerin on Insulin Resistance in Healthy Young Men

“…In this regards there are also another reports indicated that elevation of nitric oxide activity is a mechanism for lower incidence of arterial hypertension in females [4,8]. Shangjian, et al also in a study reporting higher levels of serum nitric oxide level as a compensatory mechanism in insulin resistant rats comparing with control group [9]. Other studies in healthy human subjects also indicating a direct relationship between nitric oxide production in endothelial vascular cells and insulin sensitivity [10].…”

Sibutramine, a serotonin–norepinephrine reuptake inhibitor, causes fibrosis in rats

“…Its therapeutic effects are produced mainly by the inhibition of norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake at neuronal synapse sites in the Central Nervous System (CNS). This inhibition causes an increase in the synaptic concentration of these substances and consequently an increase in the feeling of satiety and energy expenditure and a resultant decrease in food intake (Lechin et al, 2006;Eroglu et al, 2009;Sansbury BE and Hill BG, 2014). After absorption, Sibutramine is metabolized by the hepatic Cytochrome P450 enzymes, forming the pharmacologically active metabolites, M1 and M2, which are responsible for the resultant hypophagic effect and subsequent weight-loss (Hwang IC et al, 2014;Luque and Rey 2002;Padwal and Majumdar 2007).…”