DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise

Jehad Abubaker, Ali Tiss, Mohamed Abu-Farha, Fahad Al-Ghimlas, Irina Al-Khairi, Engin Baturcam, Preethi Cherian, Naser Elkum, Maha Hammad, Jeena John, Sina Kavalakatt, Abdelkrim Khadir, Samia Warsame, Said Dermime, Kazem Behbehani, Mohammed Dehbi

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 RT2-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.

Original languageEnglish
Article numbere69217
JournalPLoS One
Volume8
Issue number7
DOIs
Publication statusPublished - 24 Jul 2013
Externally publishedYes

Fingerprint

exercise
obesity
Down-Regulation
Obesity
Exercise
Medical problems
IKappaB kinase
mitogen-activated protein kinase
insulin resistance
Insulin
diabetes
Insulin Resistance
Adipose Tissue
Tunicamycin
Chemokine CCL5
Biopsy
Palmitates
tunicamycin
Chemokines
Heat-Shock Response

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Abubaker, J., Tiss, A., Abu-Farha, M., Al-Ghimlas, F., Al-Khairi, I., Baturcam, E., ... Dehbi, M. (2013). DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise. PLoS One, 8(7), [e69217]. https://doi.org/10.1371/journal.pone.0069217

DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise. / Abubaker, Jehad; Tiss, Ali; Abu-Farha, Mohamed; Al-Ghimlas, Fahad; Al-Khairi, Irina; Baturcam, Engin; Cherian, Preethi; Elkum, Naser; Hammad, Maha; John, Jeena; Kavalakatt, Sina; Khadir, Abdelkrim; Warsame, Samia; Dermime, Said; Behbehani, Kazem; Dehbi, Mohammed.

In: PLoS One, Vol. 8, No. 7, e69217, 24.07.2013.

Research output: Contribution to journalArticle

Abubaker, J, Tiss, A, Abu-Farha, M, Al-Ghimlas, F, Al-Khairi, I, Baturcam, E, Cherian, P, Elkum, N, Hammad, M, John, J, Kavalakatt, S, Khadir, A, Warsame, S, Dermime, S, Behbehani, K & Dehbi, M 2013, 'DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise', PLoS One, vol. 8, no. 7, e69217. https://doi.org/10.1371/journal.pone.0069217
Abubaker J, Tiss A, Abu-Farha M, Al-Ghimlas F, Al-Khairi I, Baturcam E et al. DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise. PLoS One. 2013 Jul 24;8(7). e69217. https://doi.org/10.1371/journal.pone.0069217
Abubaker, Jehad ; Tiss, Ali ; Abu-Farha, Mohamed ; Al-Ghimlas, Fahad ; Al-Khairi, Irina ; Baturcam, Engin ; Cherian, Preethi ; Elkum, Naser ; Hammad, Maha ; John, Jeena ; Kavalakatt, Sina ; Khadir, Abdelkrim ; Warsame, Samia ; Dermime, Said ; Behbehani, Kazem ; Dehbi, Mohammed. / DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise. In: PLoS One. 2013 ; Vol. 8, No. 7.
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