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Hepatic BSCL2 (Seipin) Deficiency Disrupts Lipid Droplet Homeostasis and Increases Lipid Metabolism via SCD1 Activity
Berardinelli-Seip congenital lipodystrophy (BSCL) is an autosomal recessive disorder. The more severe form, designated BSCL2, arises due to mutations in the BSCL2 gene. Patients with BSCL2, as well as Bscl2 −/− mice, have a near total absence of body fat, an organomegaly, and develop metabolic disor...
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Published in: | Lipids 2017-02, Vol.52 (2), p.129-150 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Berardinelli-Seip congenital lipodystrophy (BSCL) is an autosomal recessive disorder. The more severe form, designated BSCL2, arises due to mutations in the
BSCL2
gene. Patients with BSCL2, as well as
Bscl2
−/−
mice, have a near total absence of body fat, an organomegaly, and develop metabolic disorders including insulin resistance and hepatic steatosis. The function of the Seipin (BSCL2) protein remains poorly understood. Several lines of evidence have indicated that Seipin may have distinct functions in adipose versus non-adipose cells. Here we present evidence that
BSCL2
/
Bscl2
plays a role in lipid droplet (LD) biogenesis and homeostasis in primary and cultured hepatocytes. Our results show that decreasing
BSCL2
/
Bscl2
expression in hepatocytes increases the number and size of LD, as well as the expression of genes implicated in their formation and stability. We also show that knocking down
SCD1
expression reverses the phenotype associated with Seipin deficiency. Interestingly,
BSCL2
knockdown induces SCD1 expression and activity, potentially leading to increased basal phosphorylation of proteins involved in the insulin signaling cascade, as well as further increasing fatty acid uptake and
de novo
lipogenesis. In conclusion, our results suggest that a hepatic
BSCL2
/
Bscl2
deficiency induces the increase and expansion of LD, potentially via increased SCD1 activity. |
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ISSN: | 0024-4201 1558-9307 |
DOI: | 10.1007/s11745-016-4210-5 |