Nature Genetics
26, 474 - 479 (2000)
doi:10.1038/82630
Absence of perilipin results in leanness and reverses obesity in
Leprdb/db miceJavier Martinez-Botas1, John B. Anderson1, Darin Tessier1, Alexandre Lapillonne2, Benny Hung-Junn Chang1, Michael J. Quast3, David Gorenstein4, Kuang-Hua Chen1
& Lawrence Chan11
Departments of Molecular & Cellular Biology and
Medicine, Baylor College of Medicine, Houston, Texas
, USA. 2
United States Department of Agriculture/Agricultural
Research Service Children's Nutrition Research Center, Houston
, Texas, USA. 3
Marine Biomedical Institute and Department of Radiology,
University of Texas Medical Branch, Galveston, Texas
, USA. 4
the Sealy Center for Structural Biology, University
of Texas Medical Branch, Galveston, Texas,
USA.
Correspondence should be addressed to Lawrence Chan lchan@bcm.tmc.eduObesity is a disorder of energy balance1. Hormone-sensitive
lipase (HSL) mediates the hydrolysis of triacylglycerol2, the
major form of stored energy in the body. Perilipin (encoded by the gene
Plin), an adipocyte protein, has been postulated to modulate HSL activity3,
4,
5. We show here that targeted disruption of Plin results
in healthy mice that have constitutively activated fat-cell HSL. Plin
-/- mice consume more food than control mice, but have
normal body weight. They are much leaner and more muscular than controls,
have 62% smaller white adipocytes, show elevated basal lipolysis that is resistant
to  -adrenergic agonist stimulation, and are cold-sensitive except when
fed. They are also resistant to diet-induced obesity. Breeding the Plin
-/- alleles into Leprdb/db
mice reverses the obesity by increasing the metabolic rate of the mice. Our
results demonstrate a role for perilipin in reining in basal HSL activity
and regulating lipolysis and energy balance; thus, agents that inactivate
perilipin may prove useful as anti-obesity medications.
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