Thumbnail
Access Restriction
Open

Author Jeong, Ha-Won ♦ Choi, Ran Hee ♦ McClellan, Jamie L. ♦ Piroli, Gerardo G. ♦ Frizzell, Norma ♦ Tseng, Yu-Hua ♦ Goodyear, Laurie J. ♦ Koh, Ho-Jin
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ADIPOSE TISSUE ♦ BATS ♦ DRUGS ♦ IN VIVO ♦ INHIBITION ♦ INSULIN ♦ METABOLISM ♦ MICE ♦ MOLECULES ♦ PHOSPHORYLATION
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. - Highlights: • TRB3 is expressed in brown adipose tissue and its expression is increased during differentiation. • Overexpression of TRB3 inhibits differentiation and its activity. • Overexpression of TRB3 in brown preadipocytes inhibits insulin signaling. • TRB3KO mice displays improved insulin signaling in brown adipose tissue. • Insulin signaling is required for the effects of TRB3 to regulate brown adipose tissue differentiation and activity.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-02-19
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 470
Issue Number 4


Open content in new tab

   Open content in new tab