Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy.

Abstract

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance, and fatty liver. BSCL2 is caused by loss-of-function mutations in the BSCL2/seipin gene, which encodes seipin. The essential role for seipin in adipogenesis has recently been established both in vitro and in vivo. However, seipin is highly upregulated at later stages of adipocyte development, and its role in mature adipocytes remains to be elucidated. We therefore generated transgenic mice overexpressing a short isoform of human BSCL2 gene (encoding 398 amino acids) using the adipocyte-specific aP2 promoter. The transgenic mice produced ∼150% more seipin than littermate controls in white adipose tissue. Surprisingly, the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets. This may be due in part to elevated lipolysis rates in the transgenic mice. Moreover, there was a nearly 50% increase in the triacylglycerol content of transgenic liver. These results suggest that seipin promotes the differentiation of preadipocytes but may inhibit lipid storage in mature adipocytes.

• Authors: Xin Cui, Yuhui Wang, Lingjun Meng, Weihua Fei, Jingna Deng, Guoheng Xu, Xingui Peng, Shenghong Ju, Ling Zhang, George Liu, Liping Zhao, Hongyuan Yang
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 302 Issue 6 Pg. E705-13 (Mar 15 2012) ISSN: 1522-1555 [Electronic] United States
• PMID: 22234369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BSCL2 protein, human
• DNA, Complementary
• GTP-Binding Protein gamma Subunits
• Lipids
• RNA

Topics

• Adipocytes (metabolism, ultrastructure)
• Adipocytes, White (physiology)
• Adipose Tissue (metabolism)
• Animals
• Blotting, Western
• Body Temperature (physiology)
• Cell Size
• DNA, Complementary (biosynthesis, genetics)
• Eating (physiology)
• GTP-Binding Protein gamma Subunits (biosynthesis, genetics)
• Glucose Tolerance Test
• Humans
• Lipid Metabolism (genetics, physiology)
• Lipids (blood)
• Lipodystrophy, Congenital Generalized (genetics, metabolism)
• Lipolysis (physiology)
• Magnetic Resonance Imaging
• Mice
• Mice, Transgenic
• RNA (biosynthesis, genetics)
• Real-Time Polymerase Chain Reaction