title: Absence of hormone-sensitive lipase inhibits obesity and adipogenesis in Lep ob/ob mice.
abstract: Hormone-sensitive lipase (HSL) plays a crucial role in the hydrolysis of triacylglycerol and cholesteryl ester in various tissues including adipose tissues. To explore the role of HSL in the metabolism of fat and carbohydrate, we have generated mice lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) by cross-breeding HSL(-/-) mice with genetically obese Lep(ob/ob) mice. Unexpectedly, Lep(ob/ob)/HSL(-/-) mice ate less food, gained less weight, and had lower adiposity than Lep(ob/ob)/HSL(+/+) mice. Lep(ob/ob)/HSL(-/-) mice had massive accumulation of preadipocytes in white adipose tissues with increased expression of preadipocyte-specific genes (CAAT/enhancer-binding protein beta and adipose differentiation-related protein) and decreased expression of genes characteristic of mature adipocytes (CCAAT/enhancer-binding protein alpha, peroxisome proliferator activator receptor gamma, and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1). Consistent with the reduced food intake, hypothalamic expression of neuropeptide Y and agouti-related peptide was decreased. Since HSL is expressed in hypothalamus, we speculate that defective generation of free fatty acids in the hypothalamus due to the absence of HSL mediates the altered expression of these orexigenic neuropeptides. Thus, deficiency of both leptin and HSL has unmasked novel roles of HSL in adipogenesis as well as in feeding behavior.
authors.affiliation: Departments of Metabolic Diseases and Cardiovascular Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan. ishibash@jichi.ac.jp
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Shen
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tomita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Okazaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Fredric B
authors.initials: FB
authors.lastname: Kraemer
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D054369:Agouti-Related Protein; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D003433:Crosses, Genetic; D005247:Feeding Behavior; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000096:biosynthesis; D009479:Neuropeptides / Q000737:chemistry; D009765:Obesity / Q000209:etiology*; D010101:Oxygen Consumption; D011506:Proteins / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics* / Q000502:physiology*; D013696:Temperature; D013997:Time Factors
chemical_list: D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D011506:Proteins; D002787:Sterol Esterase; D003345:Corticosterone