title: DNAJB3/HSP-40 cochaperone is downregulated in obese humans and is restored by physical exercise.
abstract: Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT(2)-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity.
authors.affiliation: Biomedical Research Department, Dasman Diabetes Institute, Kuwait, Kuwait.
authors.forename: Jehad
authors.initials: J
authors.lastname: Abubaker
authors.forename: Ali
authors.initials: A
authors.lastname: Tiss
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abu-Farha
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Ghimlas
authors.forename: Irina
authors.initials: I
authors.lastname: Al-Khairi
authors.forename: Engin
authors.initials: E
authors.lastname: Baturcam
authors.forename: Preethi
authors.initials: P
authors.lastname: Cherian
authors.forename: Naser
authors.initials: N
authors.lastname: Elkum
authors.forename: Maha
authors.initials: M
authors.lastname: Hammad
authors.forename: Jeena
authors.initials: J
authors.lastname: John
authors.forename: Sina
authors.initials: S
authors.lastname: Kavalakatt
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Khadir
authors.forename: Samia
authors.initials: S
authors.lastname: Warsame
authors.forename: Said
authors.initials: S
authors.lastname: Dermime
authors.forename: Kazem
authors.initials: K
authors.lastname: Behbehani
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dehbi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015444:Exercise / Q000502:physiology*; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010168:Palmitates / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: C000610086:DNAJB3 protein, human; D050956:HSP40 Heat-Shock Proteins; D010168:Palmitates; D014415:Tunicamycin
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