Hepatic BSCL2 (Seipin) Deficiency Disrupts Lipid Droplet Homeostasis and Increases Lipid Metabolism via SCD1 Activity

Seipin regulates ER–lipid droplet contacts and cargo delivery

Seipin is an endoplasmic reticulum (ER) membrane protein implicated in lipid droplet (LD) biogenesis and mutated in severe congenital lipodystrophy (BSCL2). Here, we show that seipin is stably associated with nascent ER-LD contacts in human cells, typically via one mobile focal point per LD Seipin appears critical for such contacts since ER-LD contacts were completely missing or morphologically...

Seipin performs dissectible functions in promoting lipid droplet biogenesis and regulating droplet morphology

Seipin is necessary for both adipogenesis and lipid droplet (LD) organization in nonadipose tissues; however, its molecular function is incompletely understood. Phenotypes in the seipin-null mutant of Saccharomyces cerevisiae include aberrant droplet morphology (endoplasmic reticulum-droplet clusters and size heterogeneity) and sensitivity of droplet size to changes in phospholipid synthesis. I...

Analysis of Lipid Droplet Proteins and their Contribution to Phospholipid Homeostasis during Lipid Droplet Expansion

GLUT4 glucose transporter deficiency increases hepatic lipid production and peripheral lipid utilization.

A critical defect in type 2 diabetes is impaired insulin-stimulated glucose transport and metabolism in muscle and adipocytes. To understand the metabolic adaptations this elicits, we generated mice with targeted disruption of the GLUT4 glucose transporter in both adipocytes and muscle (AMG4KO). In contrast to total body GLUT4-null mice, AMG4KO mice exhibit normal growth, development, adipose m...

SIRT7 and hepatic lipid metabolism

The mammalian sirtuin family, consisting of NAD+-dependent class III histone/protein deacetylases, has 7 members (Greiss and Gartner, 2009). The physiological activities and pathological associations of sirtuins have been subjects of intense interest, as these are key regulators of metabolic processes that often impinge on health, aging and lifespan (Chalkiadaki and Guarente, 2012; Houtkooper e...