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Publication
Shc depletion stimulates brown fat activity in vivo and in vitro.
Authors Tomilov A, Bettaieb A, Kim K, Sahdeo S, Tomilova N, Lam A, Hagopian K, Connell
M, Fong J, Rowland D, Griffey S, Ramsey J, Haj F, Cortopassi G
Submitted By Submitted Externally on 9/20/2017
Status Published
Journal Aging cell
Year 2014
Date Published 12/1/2014
Volume : Pages 13 : 1049 - 58
PubMed Reference 25257068
Abstract 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 (ShcKO) 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 ShcKO mice. Primary ShcKO BAT
cells exhibited increased mitochondrial respiration; increased expression of
several mitochondrial and lipid-oxidative enzymes was observed in ShcKO BAT.
Levels of brown fat-specific markers of differentiation, UCP1, PRDM16, ELOVL3,
and Cox8b, were higher in ShcKO BAT. In vitro, Shc knockdown in BAT cell line
increased insulin sensitivity and metabolic activity. In vivo, pharmacological
stimulation of ShcKO 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 ShcKO mice.
Similarly, in vitro Shc knockdown in BAT cell lines increased their expression
of UCP1 and metabolic activity. These data suggest increased BAT activity
significantly contributes to the improved metabolic phenotype of ShcKO mice.




Strains
StrainDevelopment StatusCreation MethodOptions
B6.Cg-Shc1tm1PgpPhenotyping ongoingknockout
View




Genes
SymbolDescription
Shc1src homology 2 domain-containing transforming protein C1

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