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

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.

• Authors: Huan Wang, Peng-Fei Xu, Jing-Yi Li, Xue-Jing Liu, Xiao-Yue Wu, Fang Xu, Bei-Chen Xie, Xiao-Min Huang, Zi-Hao Zhou, Abudurexiti Kayoumu, George Liu, Wei Huang
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 316 Issue 1 Pg. E54-E62 (01 01 2019) ISSN: 1522-1555 [Electronic] United States
• PMID: 30457912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

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