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IL‐6 and Bile Acids are Skin‐Derived Factors that Regulate Whole‐Body Metabolism in SCD1 Deficient Mice
Author(s) -
Dumas Sabri.,
Guo Changan,
Ntambi James M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.539.10
Subject(s) - medicine , endocrinology , adipose tissue , metabolism , chemistry , lipid metabolism , bile acid , white adipose tissue , fatty acid , cholesterol 7 alpha hydroxylase , biology , biochemistry
Stearoyl‐CoA desaturase 1 (SCD1) is a lipogenic enzyme that catalyzes the rate limiting step in monounsaturated fatty acid synthesis by inserting a double bond at the delta‐9 position of long‐chain fatty acids. Specifically, SCD1 converts stearate (18:0) to oleate (18:1n9) and palmitate (16:0) to palmitoleate (16:1n7). Global deletion of SCD1 in mice (GKO) provides complete resistance to both high‐carbohydrate and high‐fat diet‐induced obesity. Furthermore, GKO mice also demonstrate improved insulin sensitivity and glucose clearance. Surprisingly, skin‐specific deletion of SCD1 also provides protection from high‐fat diet‐induced obesity and similar metabolic improvements to GKO mice. Histological analysis of SKO skin demonstrates dermal deviations that include 1) an increased number of hair follicles despite progressive hair‐loss, 2) increased macrophage infiltration and 3) differentially expressed IL‐6 that is localized around hair follicles. Co‐localization of macrophage and IL‐6 markers reveal that IL‐6 is not produced by macrophages but instead is produced by cells of the hair follicles. In plasma, IL‐6 protein levels are 25‐fold increased relative to controls, and downstream IL‐6‐mediated metabolic effects are increased at least 5‐fold in distal tissues such as white adipose tissue and liver. Another skin‐derived factor in SKO mice is bile acids, in that, genetic analysis of bile acid synthesis genes in the skin and liver of SKO mice show unexpected and divergent expression. Cyp7a1 the rate‐limiting bile acid synthesis gene is unchanged in SKO liver, but the extrahepatic equivalent Cyp7b1 is significantly increased in skin. In plasma, bile acid composition is not only increased but is also significantly skewed towards increased levels of tauro‐β‐muricholic acid which is indicative of increased extrahepatic bile acid synthesis in mice. Furthermore, the bile acid pool is also more hydrophilic which is a phenotype that is protective against the development of diseases of the metabolic syndrome. Together, changes in both IL‐6 and bile acid composition in SKO mice strongly suggest that skin metabolism is an important component of whole‐body metabolism, and this opens another avenue for the treatment of metabolic diseases. Support or Funding Information Sabrina Dumas was supported by USDA Hatch W2005 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .