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

Mohammed Dehbi²  Said Dermime⁵  Kazem Behbehani³  Naser Elkum³  Fahad Al-Ghimlas⁴  Samia Warsame¹  Sina Kavalakatt¹  Jeena John¹  Preethi Cherian¹  Irina Al-Khairi¹  Mohamed Abu-Farha¹  Jehad Abubaker¹  Abdelkrim Khadir¹  Ali Tiss¹ 

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

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

Others  :  821621
DOI  :  10.1186/1476-511X-13-106

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

【 摘 要 】

Background

Obesity 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.

Methods

Two 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.

Results

Obese 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.

Conclusion

Taken 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】

   
2014 Tiss et al.; licensee BioMed Central Ltd.

【 图 表 】

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