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Publication
Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity
during aging by regulating fat metabolism in white and brown adipose tissues.
Authors Lin L, Saha PK, Ma X, Henshaw IO, Shao L, Chang BH, Buras ED, Tong Q, Chan L,
McGuinness OP, Sun Y
Submitted By Yuxiang Sun on 9/18/2012
Status Published
Journal Aging cell
Year 2011
Date Published 12/1/2011
Volume : Pages 10 : 996 - 1010
PubMed Reference 21895961
Abstract Aging is associated with increased adiposity in white adipose tissues and
impaired thermogenesis in brown adipose tissues; both contribute to increased
incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating
orexigenic hormone that promotes adiposity. In this study, we show that ablation
of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) improves
insulin sensitivity during aging. Compared to wild-type (WT) mice, old Ghsr(-/-)
mice have reduced fat and preserve a healthier lipid profile. Old Ghsr(-/-) mice
also exhibit elevated energy expenditure and resting metabolic rate, yet have
similar food intake and locomotor activity. While GHS-R expression in white and
brown adipose tissues was below the detectable level in the young mice, GHS-R
expression was readily detectable in visceral white fat and interscapular brown
fat of the old mice. Gene expression profiles reveal that Ghsr ablation reduced
glucose/lipid uptake and lipogenesis in white adipose tissues but increased
thermogenic capacity in brown adipose tissues. Ghsr ablation prevents
age-associated decline in thermogenic gene expression of uncoupling protein 1
(UCP1). Cell culture studies in brown adipocytes further demonstrate that
ghrelin suppresses the expression of adipogenic and thermogenic genes, while
GHS-R antagonist abolishes ghrelin's effects and increases UCP1 expression.
Hence, GHS-R plays an important role in thermogenic impairment during aging.
Ghsr ablation improves aging-associated obesity and insulin resistance by
reducing adiposity and increasing thermogenesis. Growth hormone secretagogue
receptor antagonists may be a new means of combating obesity by shifting the
energy balance from obesogenesis to thermogenesis.




Strains




Genes
SymbolDescription
Ghsrgrowth hormone secretagogue receptor

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