Open AccessShc depletion stimulates brown fat activity in vivo and in vitro
Author(s) -
Tomilov Alexey,
Bettaieb Ahmed,
Kim Kyoungmi,
Sahdeo Sunil,
Tomilova Natalia,
Lam Adam,
Hagopian Kevork,
Connell Michelle,
Fong Jennifer,
Rowland Douglas,
Griffey Stephen,
Ramsey Jon,
Haj Fawaz,
Cortopassi Gino
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12267
Subject(s) - biology , brown adipose tissue , endocrinology , medicine , insulin , adipose tissue , glucose homeostasis , energy homeostasis , gene knockdown , thermogenin , mitochondrial ros , thermogenesis , insulin resistance , oxidative stress , cell culture , obesity , genetics
Summary Adipose tissue is an important metabolic organ that integrates a wide array of homeostatic processes and is crucial for whole‐body insulin sensitivity and energy metabolism. Brown adipose tissue ( BAT ) is a key thermogenic tissue with a well‐established role in energy expenditure. BAT dissipates energy and protects against both hypothermia and obesity. Thus, BAT stimulation therapy is a rational strategy for the looming pandemic of obesity, whose consequences and comorbidities have a huge impact on the aged. Shc‐deficient mice (Shc KO ) were previously shown to be lean, insulin sensitive, and resistant to high‐fat diet and obesity. We investigated the contribution of BAT to this phenotype. Insulin‐dependent BAT glucose uptake was higher in Shc KO mice. Primary Shc KO BAT cells exhibited increased mitochondrial respiration; increased expression of several mitochondrial and lipid‐oxidative enzymes was observed in Shc KO BAT . Levels of brown fat‐specific markers of differentiation, UCP 1, PRDM 16, ELOVL 3, and Cox8b, were higher in Shc KO BAT . In vitro , Shc knockdown in BAT cell line increased insulin sensitivity and metabolic activity. In vivo , pharmacological stimulation of Shc KO BAT resulted in higher energy expenditure. Conversely, pharmacological inhibition of BAT abolished the improved metabolic parameters, that is the increased insulin sensitivity and glucose tolerance of Shc KO mice. Similarly, in vitro Shc knockdown in BAT cell lines increased their expression of UCP 1 and metabolic activity. These data suggest increased BAT activity significantly contributes to the improved metabolic phenotype of Shc KO mice.