Absence of perilipin results in leanness and reverses obesity in Lepr db db mice

Citation
J. Martinez-botas et al., Absence of perilipin results in leanness and reverses obesity in Lepr db db mice, NAT GENET, 26(4), 2000, pp. 474-479
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
1061-4036 → ACNP
Volume
26
Issue
4
Year of publication
2000
Pages
474 - 479
Database
ISI
SICI code
1061-4036(200012)26:4<474:AOPRIL>2.0.ZU;2-1
Abstract
Obesity is a disorder of energy balance(1). Hormone-sensitive lipase (HSL) mediates the hydrolysis of triacylglycerol(2). the major form of stored ene rgy in the body. Perilipin (encoded by the gene Plin), an adipocyte protein , has been postulated to modulate HSL activity(3-5). We show here that targ eted disruption of Plin results in healthy mice that have constitutively ac tivated fat-cell HSL. Plin(-/-) mice consume more food than control mice, b ut have normal body weight. They are much leaner and more muscular than con trols, have 62% smaller white adipocytes, show elevated basal lipolysis tha t is resistant to beta -adrenergic agonist stimulation, and are cold-sensit ive except when fed. They are also resistant to diet-induced obesity. Breed ing the Plin(-/-) alleles into Lepr(db/db) mice reverses the obesity by inc reasing the metabolic rate of the mice. Our results demonstrate a role for perilipin in mining in basal HSL activity and regulating lipolysis and ener gy balance; thus, agents that inactivate perilipin may prove useful as anti -obesity medications.