New insights into adipose tissue dysfunction in insulin resistance

Abstract

In a state of caloric excess, adipose tissue plays an essential role by storing lipids. Its expandability determines the onset of metabolic syndrome (central obesity, dyslipidemia, glucose intolerance and hypertension). When the adipocyte endoplasmic reticulum is no longer capable of processing the excess nutrients, the so-called "endoplasmic reticulum stress" develops. This triggers efflux of free fatty acids from adipocytes into the circulation and causes triglyceride overload in skeletal muscle, liver and pancreas. Adipose tissue hypoxia then develops, due to the failure of vasculature to expand with adipocyte hypertrophy. Increased catabolism in mitochondria leads there to oxidative stress. Both phenomena cause deranged adipokine secretion and low-grade inflammation. Inflammatory cytokines, reactive oxygen species and ectopic lipid deposition are the main mediators of insulin resistance and vascular impairment, which both lead finally to diabetes type 2 and cardiovascular disease. Recently, fibrosis of adipose tissue was also demonstrated in obesity, contributing to the interplay of deleterious factors forcing inflammation. The present paper reviews recent evidence for adipose tissue dysfunction, trying to define causes and consequences. In conclusion, insulin resistance and associated complications originate from excess lipids, which cannot be stored without limit in adipose tissue, thus affecting its integrity and adipokine secretion.

Alteration of NCoR Corepressor Splicing in Mice Causes Increased Body Weight and Hepatosteatosis without Glucose Intolerance

“…Levels of these markers were elevated in the wild-type mice on the HFD compared to those on the LFD, as expected (34)(35)(36)(37)(38), and, remarkably, were still more elevated in the NCoR Ϫ/Ϫ mice on the HFD despite the glucose tolerance of the latter (Fig. 5C, D, and F).…”

Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin

“…There is expansion of the adipose tissue depots in obesity with both hyperplasia and hypertrophy, coupled with increased macrophage infiltration and, consequently, inflammation. Although obesity can lead to an expansion of the visceral depot to as much as 20% total fat mass, subcutaneous adipose tissue accounts for the remaining 80% and also responds to inflammatory insults (Mlinar & Marc 2011). Furthermore, while adipose tissue from lean individuals may preferentially secrete anti-inflammatory adipokines such as adiponectin, transforming growth factor b (TGFb), interleukin 10 (IL10), IL4, IL13, ILRa and apelin, in obesity pro-inflammatory adipocytokines such as TNFa, IL6, leptin, visfatin, resistin, angiotensin II and plasminogen activator inhibitor 1 are released, as well as several interleukins (Ouchi et al 2011) coupled with a reduction in secretion of anti-inflammatory adipokines (Table 1).…”

The association of adipose-derived dimethylarginine dimethylaminohydrolase-2 with insulin sensitivity in experimental type 2 diabetes mellitus

“…Results showed that overexpression of hDDAH-2 increased intracellular DDAH activity, decreased ADMA contents, and ameliorated insulin sensitivity by up-regulating IRS-1 and GLUT-4 expression. Since defect of insulin signal in adipocytes has been confirmed to be crucially important in metabolic diseases [27,28], we have reason to postulate that local DDAH-2 might be protective in maintaining insulin sensitivity.…”