title: Immunohistochemical profiling of the heat shock response in obese non-diabetic subjects revealed impaired expression of heat shock proteins in the adipose tissue.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ali
authors.initials: A
authors.lastname: Tiss
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Khadir
authors.forename: Jehad
authors.initials: J
authors.lastname: Abubaker
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abu-Farha
authors.forename: Irina
authors.initials: I
authors.lastname: Al-Khairi
authors.forename: Preethi
authors.initials: P
authors.lastname: Cherian
authors.forename: Jeena
authors.initials: J
authors.lastname: John
authors.forename: Sina
authors.initials: S
authors.lastname: Kavalakatt
authors.forename: Samia
authors.initials: S
authors.lastname: Warsame
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Ghimlas
authors.forename: Naser
authors.initials: N
authors.lastname: Elkum
authors.forename: Kazem
authors.initials: K
authors.lastname: Behbehani
authors.forename: Said
authors.initials: S
authors.lastname: Dermime
authors.affiliation: Diabetes Research Centre, Qatar Biomedical Research Institute, Box: 5825, Doha, Qatar. mdehbi@qf.org.qa.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dehbi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D015850:Interleukin-6 / Q000097:blood; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha