Inhibition of Sam68 triggers adipose tissue browning

Junlan Zhou, Min Cheng, Chan Boriboun, Mariam M. Ardehali, Changfei Jiang, Qinghua Liu, Shuling Han, David A. Goukassian, Yao Liang Tang, Ting C. Zhao, Ming Zhao, Lu Cai, Stéphane Richard, Raj Kishore, Gangjian Qin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis.We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders.

Original languageEnglish (US)
Pages (from-to)181-189
Number of pages9
JournalJournal of Endocrinology
Volume225
Issue number3
DOIs
StatePublished - Jan 1 2015

Fingerprint

Mitosis
Adipose Tissue
Knockout Mice
Adiposity
White Adipose Tissue
Brown Adipose Tissue
Groin
Obesity
Body Weight
Thermogenesis
High Fat Diet
Adipocytes
Type 2 Diabetes Mellitus
Energy Metabolism
Genes
Insulin Resistance
Homeostasis
Fatty Acids
Eating
Fats

Keywords

  • Adipocyte
  • Insulin
  • Metabolism
  • Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Zhou, J., Cheng, M., Boriboun, C., Ardehali, M. M., Jiang, C., Liu, Q., ... Qin, G. (2015). Inhibition of Sam68 triggers adipose tissue browning. Journal of Endocrinology, 225(3), 181-189. https://doi.org/10.1530/JOE-14-0727

Inhibition of Sam68 triggers adipose tissue browning. / Zhou, Junlan; Cheng, Min; Boriboun, Chan; Ardehali, Mariam M.; Jiang, Changfei; Liu, Qinghua; Han, Shuling; Goukassian, David A.; Tang, Yao Liang; Zhao, Ting C.; Zhao, Ming; Cai, Lu; Richard, Stéphane; Kishore, Raj; Qin, Gangjian.

In: Journal of Endocrinology, Vol. 225, No. 3, 01.01.2015, p. 181-189.

Research output: Contribution to journalArticle

Zhou, J, Cheng, M, Boriboun, C, Ardehali, MM, Jiang, C, Liu, Q, Han, S, Goukassian, DA, Tang, YL, Zhao, TC, Zhao, M, Cai, L, Richard, S, Kishore, R & Qin, G 2015, 'Inhibition of Sam68 triggers adipose tissue browning', Journal of Endocrinology, vol. 225, no. 3, pp. 181-189. https://doi.org/10.1530/JOE-14-0727
Zhou J, Cheng M, Boriboun C, Ardehali MM, Jiang C, Liu Q et al. Inhibition of Sam68 triggers adipose tissue browning. Journal of Endocrinology. 2015 Jan 1;225(3):181-189. https://doi.org/10.1530/JOE-14-0727
Zhou, Junlan ; Cheng, Min ; Boriboun, Chan ; Ardehali, Mariam M. ; Jiang, Changfei ; Liu, Qinghua ; Han, Shuling ; Goukassian, David A. ; Tang, Yao Liang ; Zhao, Ting C. ; Zhao, Ming ; Cai, Lu ; Richard, Stéphane ; Kishore, Raj ; Qin, Gangjian. / Inhibition of Sam68 triggers adipose tissue browning. In: Journal of Endocrinology. 2015 ; Vol. 225, No. 3. pp. 181-189.
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