Skin-specific deletion of stearoyl-CoA desaturase-1 alters skin lipid composition and protects mice from high fat diet-induced obesity.
Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids and is an important regulator of whole body energy homeostasis. Severe cutaneous changes in mice globally deficient in SCD1 also indicate a role for SCD1 in maintaining skin lipids. We have generated mice with a skin-specific deletion of SCD1 (SKO) and report here that SKO mice display marked sebaceous gland hypoplasia and depletion of sebaceous lipids. In addition, SKO mice have significantly increased energy expenditure and are protected from high fat diet-induced obesity, thereby recapitulating the hypermetabolic phenotype of global SCD1 deficiency. Genes of fat oxidation, lipolysis, and thermogenesis, including uncoupling proteins and peroxisome proliferator-activated receptor-gamma co-activator-1alpha, are up-regulated in peripheral tissues of SKO mice. However, unlike mice globally deficient in SCD1, SKO mice have an intact hepatic lipogenic response to acute high carbohydrate feeding. Despite increased basal thermogenesis, SKO mice display severe cold intolerance because of rapid depletion of fuel substrates, including hepatic glycogen, to maintain core body temperature. These data collectively indicate that SKO mice have increased cold perception because of loss of insulating factors in the skin. This results in up-regulation of thermogenic processes for temperature maintenance at the expense of fuel economy, illustrating cross-talk between the skin and peripheral tissues in maintaining energy homeostasis.
Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Harini
H
Sampath
Matthew T
MT
Flowers
Xueqing
X
Liu
Chad M
CM
Paton
Ruth
R
Sullivan
Kiki
K
Chu
Minghui
M
Zhao
James M
JM
Ntambi
D000064:Acclimatization; D000818:Animals; D003080:Cold Temperature; D004041:Dietary Fats / Q000009:adverse effects*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism; D007003:Hypoglycemia / Q000235:genetics; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012868:Skin Abnormalities / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism*
D004041:Dietary Fats; D005227:Fatty Acids; D008055:Lipids; D006003:Glycogen; D013230:Stearoyl-CoA Desaturase