Chronic unpredictable stress regulates visceral adipocyte‐mediated glucose metabolism and inflammatory circuits in male rats

Physiological Reports

Iordanes Karagiannides³  Viktoriya Golovatscka¹  Kyriaki Bakirtzi³  Aristea Sideri³  Martha Salas¹  Dimitris Stavrakis³  Christos Polytarchou²  Dimitrios Iliopoulos²  Charalabos Pothoulakis³ 

[1] Division of Digestive Diseases, Center for Neurobiology of Stress, CURE VAGLA HC, Los Angeles, California;Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts;Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California

关键词: Adipocytes;    adipokines;    fat tissue;    insulin resistance;    stress;   

DOI  :  10.14814/phy2.284

来源: Wiley

【 摘 要 】

Abstract

Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte-associated insulin sensitivity and function after chronic unpredictable stress in rats. Male rats were subjected to chronic unpredictable stress for 35 days. Total body and visceral fat was measured. Cytokines and activated intracellular kinase levels were determined using high-throughput multiplex assays. Adipocyte function was assessed via tritiated glucose uptake assay. Stressed rats showed no weight gain, and their fat/lean mass ratio increased dramatically compared to control animals. Stressed rats had significantly higher mesenteric fat content and epididymal fat pad weight and demonstrated reduced serum glucose clearing capacity following glucose challenge. Alterations in fat depot size were mainly due to changes in adipocyte numbers and not size. High-throughput molecular screening in adipocytes isolated from stressed rats revealed activation of intracellular inflammatory, glucose metabolism, and MAPK networks compared to controls, as well as significantly reduced glucose uptake capacity in response to insulin stimulation. Our study identifies the adipocyte as a key regulator of the effects of chronic stress on insulin resistance, and glucose metabolism, with important ramifications in the pathophysiology of several stress-related disease states.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.