Chronic Ethanol‐Induced Insulin Resistance Is Associated With Macrophage Infiltration Into Adipose Tissue and Altered Expression of Adipocytokines

Abstract

These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.

Identification of a Cytochrome P4502E1/Bid/C1q-dependent Axis Mediating Inflammation in Adipose Tissue after Chronic Ethanol Feeding to Mice

“…The development of adipose tissue inflammation in obese animals is associated with an increase in body weight and adipocyte size (33). In contrast, ethanol feeding is not associated with increased body weight, adiposity, or adipocyte size (3,5), suggesting that adipose inflammation in response to ethanol is initiated via a mechanism(s) distinct from those involved in obesity-induced adipose inflammation. Ethanol metabolism via CYP2E1 increases oxidative stress and is a well studied contributor to alcoholic liver disease (12).…”

“…6). Ethanol exposure is associated with the development of oxidant stress in a number of tissues (12) including adipose tissue (3,4). In the liver, ethanol-induced oxidant stress is due at least in part to ethanol metabolism via CYP2E1 (12).…”

“…Expression of inflammatory cytokines and macrophage infiltration into adipose tissue are also increased, and adipocytes exhibit insulin resistance (3). Both insulin-stimulated glucose transport and the ability of insulin to inhibit lipolysis are reduced after chronic ethanol feeding (3) associated with the development of systemic insulin resistance and the development of hepatic steatosis (5).…”

“…After chronic ethanol feeding, indicators of oxidative stress, such as 4-hydroxynonenal, are detected in adipose tissue (3,4). Expression of inflammatory cytokines and macrophage infiltration into adipose tissue are also increased, and adipocytes exhibit insulin resistance (3).…”

Chronic Ethanol and Triglyceride Turnover in White Adipose Tissue in Rats

“…Hyperinsulinemic-euglycemic clamps were then performed on one rat at a time as previously described (17), with minor modifications. Data on the effects of chronic ethanol on glucose disposal during these specific clamp studies have been previously reported (18). Briefly, rats were transported from the Animal Resource Center and allowed at least 90 min to stabilize before commencement of the glucose clamp.…”