Document Detail


Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue.
MedLine Citation:
PMID:  23020201     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin sensitivity deteriorates with age, but mechanisms remain unclear. Age-related changes in the function of subcutaneous white adipose tissue (sWAT) are less characterized than those in visceral WAT. We hypothesized that metabolic alterations in sWAT, which in contrast to epididymal WAT, harbors a subpopulation of energy-dissipating UCP1+ brown adipocytes, promote age-dependent progression toward insulin resistance. Indeed, we show that a predominant consequence of aging in murine sWAT is loss of 'browning'. sWAT from young mice is histologically similar to brown adipose tissue (multilocular, UCP1+), but becomes morphologically white by 12 months of age. Correspondingly, sWAT expression of ucp1 precipitously declines (~300-fold) between 3 and 12 months. Loss continues into old age (24 months) and is inversely correlated with the development of insulin resistance. Additional age-dependent changes in sWAT include lower expression of adbr3 and higher expression of maoa, suggesting reduced local adrenergic tone as a potential mechanism. Indeed, treatment with a β3-adrenergic agonist to compensate for reduced tone rescues the aged sWAT phenotype. Age-related changes in sWAT are not explained by the differences in body weight; mice subjected to 40% caloric restriction for 12 months are of body weight similar to 3-month-old ad lib fed mice, but display sWAT resembling that of age-matched ad lib fed mice (devoid of brown adipose-like morphology). Overall, findings identify the loss of 'browning' in sWAT as a new aging phenomenon and provide insight into the pathogenesis of age-associated metabolic disease by revealing novel molecular changes tied to systemic metabolic dysfunction.
Authors:
Nicole H Rogers; Alejandro Landa; Seongjoon Park; Roy G Smith
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-24
Journal Detail:
Title:  Aging cell     Volume:  11     ISSN:  1474-9726     ISO Abbreviation:  Aging Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-04-18     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  101130839     Medline TA:  Aging Cell     Country:  England    
Other Details:
Languages:  eng     Pagination:  1074-83     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes, Brown / drug effects,  metabolism,  pathology*
Adipose Tissue, Brown / drug effects,  metabolism,  pathology*
Adipose Tissue, White / drug effects,  metabolism,  pathology*
Adrenergic beta-Agonists / pharmacology
Aging / genetics,  metabolism,  pathology*
Animals
Body Weight
Gene Expression / drug effects
Humans
Insulin / metabolism
Insulin Resistance
Ion Channels / genetics,  metabolism
Male
Mice
Mice, Inbred C57BL
Mitochondrial Proteins / genetics,  metabolism
Monoamine Oxidase / genetics,  metabolism
Obesity / genetics,  metabolism,  pathology
Phenotype
Receptors, Adrenergic, beta-3 / genetics,  metabolism
Subcutaneous Tissue / drug effects,  metabolism,  pathology*
Grant Support
ID/Acronym/Agency:
R01 AG019230/AG/NIA NIH HHS; R01 AG029740/AG/NIA NIH HHS; R01AG19230/AG/NIA NIH HHS; R01AG29740/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Insulin; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Receptors, Adrenergic, beta-3; 0/mitochondrial uncoupling protein; EC 1.4.3.4/Monoamine Oxidase
Comments/Corrections

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