title: Liver-Specific Silencing of Lipin1 Reduces Fat Mass as Well as Hepatic Triglyceride Biosynthesis in Mice.
abstract: Lipin1, a bifunctional protein, regulates fatty acid utilization in the triglyceride biosynthesis pathway. In the current study, using a liver-specific in vivo short interfering RNA (siRNA) delivery system, we examined the pathological and physiological roles of hepatic Lipin1 in the development of insulin resistance and the maintenance of systemic energy homeostasis. Liver-specific silencing of Lipin1 expression was achieved by the systemic administration of siRNA against Lpin1 mRNA (siLpin1)-loaded lipid nanoparticles (LNPs) to wild type mice at 3-4 d intervals for 25 d. The siLpin1-treated mice showed normal blood glucose levels and insulin sensitivity, however, triglyceride (TG) levels were reduced in liver and peripheral blood of them. The knockdown of hepatic Lipin1 in mice led to marked decrease in adipose tissue mass and adipocyte diameters in epididymal and inguinal fat depots without the undesired silencing of Lipin1 in adipose tissue. In summary, we report for the first time that the down-regulation of hepatic Lipin1 expression leads to less adiposity as well as a decrease in TG level in the liver and blood circulation, without any alterations in the glucose tolerance and blood glucose levels. Our findings may provide new insights into the physiological roles of hepatic Lipin1 in systemic energy homeostasis.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kajimoto
authors.forename: Erina
authors.initials: E
authors.lastname: Suemitsu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Yu
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D020868:Gene Silencing; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage; D009687:Nuclear Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D010711:Phosphatidate Phosphatase / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014280:Triglycerides / Q000096:biosynthesis* / Q000097:blood
chemical_list: D001786:Blood Glucose; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014280:Triglycerides; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase