Possible Mechanisms of Insulin Resistance in Obese Subjects.
Obesity is characterized by excessive triglyceride accumulation in adipose tissue cells (adipocytes); the adipocytes are not just a reservoir for storage of energy in the form of triglyceride, but more importantly act as endocrine cells; they secrete several hormones as leptin and adiponectin, also secrete adipokines as TNF-α, Interleukin 6 (IL-6) and Plasminogen activator inhibitor-1 (PAI-1). In obese subjects, adipocytes release high levels of free fatty acids (FFA) and its metabolites; Diacylglycerol (DAG) and ceramide.
Those mechanisms include; inflammatory pathways through activation of (IKKβ) (inhibitor of nuclear factor κB) and c-Jun N-terminal kinase 1 (JNK1): They play a role in feedback inhibition of the insulin signaling cascade. Their activation occur by increased secretion of free fatty acids (FFA) and its metabolites, which together adipokines (TNF-α), reactive oxygen species in both liver and adipose tissue. Its inhibition decreases triglyceride storage in adipocytes and increases lipid distribution to skeletal muscle and liver which consequently contributes to insulin resistance.
Also Leptin and adiponectin under normal conditions promote FA oxidation, lower lipid stores.
Apolipoprotein (ApoB 100) is the major constituent of very low density lipoprotein (VLDL) and low density lipoprotein (LDL). Insulin decreases ApoB 100 secretion by promoting its degradation in the hepatocyte. Also insulin promotes clearance of circulating ApoB 100 particles by the hepatocytes through low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1). In conclusion there are several hypotheses for the pathogenesis of obesity-associated insulin resistance, including chronic inflammation and its contribution to decreased insulin secretion and dyslipidemia. Moreover, the possible role added by lipoproteins and their associated apoproteins; that help in modulating insulin sensitivity.
Obes Res Open J. 2016; 2(4): 117-118. doi: 10.17140/OROJ-2-118
