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The more severe form, designated BSCL2, arises due to mutations in the <jats:italic>BSCL2<\/jats:italic> gene. Patients with BSCL2, as well as <jats:italic>Bscl2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> 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\u2010adipose cells. Here we present evidence that <jats:italic>BSCL2<\/jats:italic>\/<jats:italic>Bscl2<\/jats:italic> plays a role in lipid droplet (LD) biogenesis and homeostasis in primary and cultured hepatocytes. Our results show that decreasing <jats:italic>BSCL2<\/jats:italic>\/<jats:italic>Bscl2<\/jats:italic> 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 <jats:italic>SCD1<\/jats:italic> expression reverses the phenotype associated with Seipin deficiency. Interestingly, <jats:italic>BSCL2<\/jats:italic> 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 <jats:italic>de novo<\/jats:italic> lipogenesis. In conclusion, our results suggest that a hepatic <jats:italic>BSCL2<\/jats:italic>\/<jats:italic>Bscl2<\/jats:italic> deficiency induces the increase and expansion of LD, potentially via increased SCD1 activity.<\/jats:p>","DOI":"10.1007\/s11745-016-4210-5","type":"journal-article","created":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T23:56:15Z","timestamp":1478908575000},"page":"129-150","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Hepatic BSCL2 (Seipin) Deficiency Disrupts Lipid Droplet Homeostasis and Increases Lipid Metabolism via SCD1 Activity"],"prefix":"10.1002","volume":"52","author":[{"given":"Mohamed Amine","family":"Lounis","sequence":"first","affiliation":[{"name":"D\u00e9partement des sciences biologiques et centre de recherche BioMed Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al Case Postale 8888, Succursale Centre\u2010ville Montr\u00e9al QC H3C 3P8 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