[PDF][PDF] Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration

P Polak, N Cybulski, JN Feige, J Auwerx, MA Rüegg… - Cell metabolism, 2008 - cell.com
P Polak, N Cybulski, JN Feige, J Auwerx, MA Rüegg, MN Hall
Cell metabolism, 2008cell.com
Summary raptor is a specific and essential component of mammalian TOR complex 1
(mTORC1), a key regulator of cell growth and metabolism. To investigate a role of adipose
mTORC1 in regulation of adipose and whole-body metabolism, we generated mice with an
adipose-specific knockout of raptor (raptor ad−/−). Compared to control littermates, raptor
ad−/− mice had substantially less adipose tissue, were protected against diet-induced
obesity and hypercholesterolemia, and exhibited improved insulin sensitivity. Leanness was …
Summary
raptor is a specific and essential component of mammalian TOR complex 1 (mTORC1), a key regulator of cell growth and metabolism. To investigate a role of adipose mTORC1 in regulation of adipose and whole-body metabolism, we generated mice with an adipose-specific knockout of raptor (raptorad−/−). Compared to control littermates, raptorad−/− mice had substantially less adipose tissue, were protected against diet-induced obesity and hypercholesterolemia, and exhibited improved insulin sensitivity. Leanness was in spite of reduced physical activity and unaffected caloric intake, lipolysis, and absorption of lipids from the food. White adipose tissue of raptorad−/− mice displayed enhanced expression of genes encoding mitochondrial uncoupling proteins characteristic of brown fat. Leanness of the raptorad−/− mice was attributed to elevated energy expenditure due to mitochondrial uncoupling. These results suggest that adipose mTORC1 is a regulator of adipose metabolism and, thereby, controls whole-body energy homeostasis.
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