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Cell Rep. 2016 Dec 6;17(10):2542-2552. doi: 10.1016/j.celrep.2016.10.040.

Rapamycin Reverses Metabolic Deficits in Lamin A/C-Deficient Mice.

Author information

1
Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA.
2
Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA. Electronic address: bkennedy@buckinstitute.org.

Abstract

The role of the mTOR inhibitor, rapamycin, in regulation of adiposity remains controversial. Here, we evaluate mTOR signaling in lipid metabolism in adipose tissues of Lmna-/- mice, a mouse model for dilated cardiomyopathy and muscular dystrophy. Lifespan extension by rapamycin is associated with increased body weight and fat content, two phenotypes we link to suppression of elevated energy expenditure. In both white and brown adipose tissue of Lmna-/- mice, we find that rapamycin inhibits mTORC1 but not mTORC2, leading to suppression of elevated lipolysis and restoration of thermogenic protein UCP1 levels, respectively. The short lifespan and metabolic phenotypes of Lmna-/- mice can be partially rescued by maintaining mice at thermoneutrality. Together, our findings indicate that altered mTOR signaling in Lmna-/- mice leads to a lipodystrophic phenotype that can be rescued with rapamycin, highlighting the effect of loss of adipose tissue in Lmna-/- mice and the consequences of altered mTOR signaling.

KEYWORDS:

Lmna(−/−) mice; adiposity; lifespan; lipodystrophy; mTOR; progeria; rapamycin; thermoneutrality

PMID:
27926859
DOI:
10.1016/j.celrep.2016.10.040
[Indexed for MEDLINE]
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