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Biochem Biophys Res Commun. 2016 Feb 19;470(4):783-91. doi: 10.1016/j.bbrc.2016.01.064. Epub 2016 Jan 20.

Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling.

Author information

1
Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, SC 29208, USA.
2
Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
3
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
4
Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, SC 29208, USA. Electronic address: kohh@mailbox.sc.edu.

Abstract

Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti-obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found that TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function.

KEYWORDS:

Brown adipose tissue; Insulin signaling; UCP1

PMID:
26801556
PMCID:
PMC4768059
DOI:
10.1016/j.bbrc.2016.01.064
[Indexed for MEDLINE]
Free PMC Article

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