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Mol Metab. 2013 Nov 28;3(2):145-54. doi: 10.1016/j.molmet.2013.11.008. eCollection 2014 Apr.

Lipin-1 and lipin-3 together determine adiposity in vivo.

Author information

1
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
2
Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
3
Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Alberta, Canada.
4
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA ; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
5
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA ; Current address: Department of Energy (DOE) Joint Genome Institute, Walnut Creek, CA 94598, USA.
6
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
7
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
8
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA ; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA ; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Abstract

The lipin protein family of phosphatidate phosphatases has an established role in triacylglycerol synthesis and storage. Physiological roles for lipin-1 and lipin-2 have been identified, but the role of lipin-3 has remained mysterious. Using lipin single- and double-knockout models we identified a cooperative relationship between lipin-3 and lipin-1 that influences adipogenesis in vitro and adiposity in vivo. Furthermore, natural genetic variations in Lpin1 and Lpin3 expression levels across 100 mouse strains correlate with adiposity. Analysis of PAP activity in additional metabolic tissues from lipin single- and double-knockout mice also revealed roles for lipin-1 and lipin-3 in spleen, kidney, and liver, for lipin-1 alone in heart and skeletal muscle, and for lipin-1 and lipin-2 in lung and brain. Our findings establish that lipin-1 and lipin-3 cooperate in vivo to determine adipose tissue PAP activity and adiposity, and may have implications in understanding the protection of lipin-1-deficient humans from overt lipodystrophy.

KEYWORDS:

Adipogenesis; Gene family; Glycerolipid biosynthesis; Knockout mouse; Triacylglycerol

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