Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue

Lipids in Health and Disease

Research

Naser Elkum¹  Ali Tiss²  Sina Kavalakatt²  Mohamed Abu-Farha²  Irina Al-Khairi²  Jehad Abubaker²  Jeena John²  Samia Warsame²  Abdelkrim Khadir²  Preethi Cherian²  Kazem Behbehani³  Said Dermime⁴  Mohammed Dehbi⁵  Fahad Al-Ghimlas⁶ 

[1] Department Biostatistics and Epidemiology, Dasman Diabetes Institute, Kuwait City, Kuwait;Department of Biomedical Research, Dasman Diabetes Institute, Kuwait City, Kuwait;Department of Biomedical Research, Dasman Diabetes Institute, Kuwait City, Kuwait;Fitness and Rehabilitation Center, Dasman Diabetes Institute, Kuwait City, Kuwait;Department Biostatistics and Epidemiology, Dasman Diabetes Institute, Kuwait City, Kuwait;Department of Biomedical Research, King Fahad Specialist Hospital, Dammam, Kingdom of Saudi Arabia;Diabetes Research Centre, Qatar Biomedical Research Institute, Box: 5825, Doha, Qatar;Fitness and Rehabilitation Center, Dasman Diabetes Institute, Kuwait City, Kuwait;

关键词: Heat shock protein;    HSP;    Exercise;    ER stress;    Obesity;    Adipose tissue;   

DOI  :  10.1186/1476-511X-13-106

 received in 2014-04-26, accepted in 2014-06-17,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundObesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels.MethodsTwo groups of adult non-diabetic human subjects consisting of lean and obese (n = 47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP-40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRT-PCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects.ResultsObese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P < 0.05). No differential expression was observed for HSP-27 between the two groups. Higher levels of HSP-72 and GRP-94 proteins correlated positively with the indices of obesity (body mass index and percent body fat) and circulating levels of IFN-gamma-inducible protein 10 (IP-10) and RANTES chemokines. This expression pattern was concomitant with increased inflammatory response in the adipose tissue as monitored by increased levels of Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and RANTES (P < 0.05). Physical exercise reduced the expression of various HSPs in obese to normal levels observed in lean subjects with a parallel decrease in the endogenous levels of IL-6, TNF-α, and RANTES.ConclusionTaken together, these data indicate that obesity triggers differential regulation of various components of the HSR in non-diabetic subjects and a 3-month physical moderate exercise was sufficient to restore the normal expression of HSPs in the adipose tissue with concomitant attenuation in the inflammatory response.

【 授权许可】

Unknown   
© Tiss et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.