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

Biochemical and Biophysical Research Communications
Ha-Won JeongHo-Jin Koh

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 phosphorylat...Continue Reading

References

Dec 13, 2000·Molecular and Cellular Biology·M FasshauerC R Kahn
Jun 17, 2003·The Journal of Biological Chemistry·Amelia J EntinghC Ronald Kahn
Feb 18, 2004·Molecular and Cellular Biology·Yu-Hua TsengC Ronald Kahn
Mar 12, 2004·American Journal of Physiology. Cell Physiology·Nobuharu FujiiLaurie J Goodyear
Jun 24, 2006·Science·Ling QiMarc Montminy
Jan 9, 2007·Biochemical and Biophysical Research Communications·Satomi Kato, Keyong Du
Apr 10, 2009·The New England Journal of Medicine·Wouter D van Marken LichtenbeltG J Jaap Teule
Apr 10, 2009·The New England Journal of Medicine·Aaron M CypessC Ronald Kahn
Apr 10, 2009·The New England Journal of Medicine·Kirsi A VirtanenPirjo Nuutila
Apr 3, 2010·Circulation Research·Joan AveryAnthony J Muslin
Jul 12, 2011·Nature Cell Biology·Lei SunHarvey F Lodish
Feb 7, 2012·The Journal of Clinical Investigation·Marica BordicchiaSheila Collins
Dec 12, 2012·The Journal of Clinical Investigation·Kristin I StanfordLaurie J Goodyear
Mar 1, 2013·Nutrition & Diabetes·C L PlaisierL Vergnes
May 23, 2013·Nature Communications·Ho-Jin KohLaurie J Goodyear
Jun 21, 2013·The Journal of Clinical Endocrinology and Metabolism·Guy H E J VijgenPatrick Schrauwen

❮ Previous
Next ❯

Citations

Nov 1, 2021·The Journal of Clinical Endocrinology and Metabolism·Seul Ki LeeYeon Jin Jang

❮ Previous
Next ❯

Related Concepts

Related Feeds

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.

Antiparasitics

Antiparasitics are medications which are indicated for the treatment of parasitic diseases. Discover the latest research on antiparasitics here.