title: Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice.
abstract: Obesity is a common nutritional problem often associated with diabetes, insulin resistance, and fatty liver (excess fat deposition in liver). Leptin-deficient Lep(ob)/Lep(ob) mice develop obesity and those obesity-related syndromes. Increased lipogenesis in both liver and adipose tissue of these mice has been suggested. We have previously shown that the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) plays a crucial role in the regulation of lipogenesis in vivo. To explore the possible involvement of SREBP-1 in the pathogenesis of obesity and its related syndromes, we generated mice deficient in both leptin and SREBP-1. In doubly mutant Lep(ob/ob) x Srebp-1(-/-) mice, fatty livers were markedly attenuated, but obesity and insulin resistance remained persistent. The mRNA levels of lipogenic enzymes such as fatty acid synthase were proportional to triglyceride accumulation in liver. In contrast, the mRNA abundance of SREBP-1 and lipogenic enzymes in the adipose tissue of Lep(ob)/Lep(ob) mice was profoundly decreased despite sustained fat, which could explain why the SREBP-1 disruption had little effect on obesity. In conclusion, SREBP-1 regulation of lipogenesis is highly involved in the development of fatty livers but does not seem to be a determinant of obesity in Lep(ob)/Lep(ob) mice.
authors.affiliation: Department of Internal Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Hasty
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ide
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Michiyo
authors.initials: M
authors.lastname: Amemiya-Kudo
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tomita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.forename: Takanari
authors.initials: T
authors.lastname: Gotoda
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005234:Fatty Liver / Q000628:therapy*; D005838:Genotype; D007333:Insulin Resistance / Q000235:genetics*; D020738:Leptin / Q000096:biosynthesis; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; D008071:Lipoprotein Lipase