SEC16B identified as a regulator of VLDL secretion and lipid accumulation in the liver
Hossein Ardehali
Hossein Ardehali
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Commentary

SEC16B identified as a regulator of VLDL secretion and lipid accumulation in the liver

Abstract

The liver plays a major role in regulating the metabolic fate of lipids and facilitates lipid secretion to peripheral organs in the form of VLDLs or lipid storage in lipid droplets (LDs). Hepatic regulation of excess lipids profoundly influences the development of atherosclerosis; thus, uncovering the regulatory mechanisms underlying lipid storage and secretion pathways may reveal additional therapeutic targets. In this issue of the JCI, Lu et al. identified a pathway involving SEC16B, showing that this protein functions as a lipid-responsive regulator and mediates VLDL secretion and LD formation to maintain lipid homeostasis. They also demonstrated that a reduction in SEC16B reduced serum lipid levels and atherosclerotic plaque area in Ldlr–/– mice. These results indicate that SEC16B connects VLDL and LD metabolism, positioning SEC16B as a potential therapeutic avenue for atherosclerosis.

Authors

Hossein Ardehali

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Figure 1

SEC16B maintains hepatic lipid homeostasis by regulating VLDL secretion and LD formation.

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SEC16B maintains hepatic lipid homeostasis by regulating VLDL secretion ...
GWAS identified associations between SEC16B expression and serum cholesterol levels, obesity, and BMI. Here, Lu et al. (5) identified that SEC16B expression increased in response to FA and lipids and was controlled by the transcription factor HNF4α, which regulates expression of key hepatic genes. Using a combination of human hepatocytes and mouse models, they determined that SEC16B KO blocked VLDL secretion from the liver by disrupting the interaction of the COPII components SEC13 and SEC31A. SEC16B KO was also associated with decreased LD size and reduced atherosclerotic plaque formation. Thus, SEC16B represents a link between VLDL secretion and hepatic lipid storage that could potentially be targeted in atherosclerosis and metabolic disorders.