Adipose tissue transplantation ameliorates lipodystrophy-associated metabolic disorders in seipin-deficient mice

Am J Physiol Endocrinol Metab. 2019 Jan 1;316(1):E54-E62. doi: 10.1152/ajpendo.00180.2018. Epub 2018 Nov 20.

Abstract

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue and can lead to hepatic steatosis, insulin resistance (IR), and dyslipidemia in humans. Adipose tissue secretes many adipokines that are central to the regulation of metabolism. In this study, we investigated whether transplantation of normal adipose tissue could ameliorate severe hepatic steatosis, IR, and dyslipidemia in lipoatrophic seipin knockout (SKO) mice. Normal adipose tissue from wild-type mice was transplanted into 6-wk-old SKO mice. At 4 mo after adipose tissue transplantation (AT), the transplanted fat survived with detectable blood vessels, and the reduced levels of plasma leptin, a major adipokine, were dramatically increased. Severe hepatic steatosis, IR, and dyslipidemia in SKO mice were ameliorated after AT. In addition, abnormal hepatic lipogenesis and β-oxidation gene expression in SKO mice were improved after AT. Our results suggest that AT may be an effective treatment to improve lipodystrophy-associated metabolic disorders.

Keywords: adipose tissue transplantation; hepatic steatosis; insulin resistance; leptin; metabolic disorders; seipin.

Publication types

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

MeSH terms

  • Animals
  • Dyslipidemias / etiology
  • Dyslipidemias / genetics
  • Dyslipidemias / metabolism
  • Fatty Acids, Nonesterified / metabolism*
  • Fatty Liver / etiology
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • GTP-Binding Protein gamma Subunits
  • Glucose Tolerance Test
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Leptin / genetics*
  • Leptin / metabolism
  • Lipid Metabolism
  • Lipodystrophy, Congenital Generalized / complications
  • Lipodystrophy, Congenital Generalized / genetics*
  • Lipodystrophy, Congenital Generalized / metabolism
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Subcutaneous Fat / transplantation*
  • Triglycerides / metabolism

Substances

  • Bscl2 protein, mouse
  • Fatty Acids, Nonesterified
  • GTP-Binding Protein gamma Subunits
  • Leptin
  • Triglycerides
  • Heterotrimeric GTP-Binding Proteins