Interleukin-6 derived from cutaneous deficiency of stearoyl-CoA desaturase- 1 may mediate metabolic organ crosstalk among skin, adipose tissue and liver

Biochem Biophys Res Commun. 2019 Jan 1;508(1):87-91. doi: 10.1016/j.bbrc.2018.11.083. Epub 2018 Nov 22.

Abstract

Stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme that adds a double bond at the delta 9 position of stearate (C18: 0) and palmitate (C16: 0), has been proven to be important in the development of obesity. Mice with skin-specific deficiency of SCD1 (SKO) display increased whole-body energy expenditure, which is protective against adiposity from a high-fat diet because it improves glucose clearance, insulin sensitivity, and hepatic steatosis. Of note, these mice also display elevated levels of the "pro-inflammatory" plasma interleukin-6 (IL-6). In whole skin of SKO mice, IL-6 mRNA levels are increased, and protein expression is evident in hair follicle cells and in keratinocytes. Recently, the well-known role of IL-6 in causing white adipose tissue lipolysis has been linked to indirectly activating the gluconeogenic enzyme pyruvate carboxylase 1 in the liver, thereby increasing hepatic glucose production. In this study, we suggest that skin-derived IL-6 leads to white adipose tissue lipolysis, which contributes to the lean phenotype of SKO mice without the incidence of meta-inflammation that is associated with IL-6 signaling.

Keywords: Adipose; Diabetes; Fat; Gluconeogenesis; Glucose; IL6; Inflammation; Lipids; Liver; Metabolism; Obesity; SCD1; Skin; Steatosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue, White / metabolism
  • Adiposity
  • Animals
  • Diet, High-Fat / adverse effects
  • Fatty Acids / metabolism
  • Gluconeogenesis
  • Hair Follicle / cytology
  • Hair Follicle / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Keratinocytes / metabolism
  • Lipolysis
  • Liver / metabolism
  • Macrophages / cytology
  • Male
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Skin / cytology
  • Skin / metabolism*
  • Stearoyl-CoA Desaturase / deficiency*
  • Stearoyl-CoA Desaturase / genetics
  • Thinness / genetics
  • Thinness / metabolism
  • Tissue Distribution

Substances

  • Fatty Acids
  • Interleukin-6
  • RNA, Messenger
  • interleukin-6, mouse
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase