Lipin, a lipodystrophy and obesity gene.
Lipodystrophy and obesity represent extreme and opposite ends of the adiposity spectrum and have typically been attributed to alterations in the expression or function of distinct sets of genes. We previously demonstrated that lipin deficiency impairs adipocyte differentiation and causes lipodystrophy in the mouse. Using two different tissue-specific lipin transgenic mouse strains, we now demonstrate that enhanced lipin expression in either adipose tissue or skeletal muscle promotes obesity. This occurs through diverse mechanisms in the two tissues, with lipin levels in adipose tissue influencing the fat storage capacity of the adipocyte, and lipin levels in skeletal muscle acting as a determinant of whole-body energy expenditure and fat utilization. Thus, variations in lipin levels alone are sufficient to induce extreme states of adiposity and may represent a mechanism by which adipose tissue and skeletal muscle modulate fat mass and energy balance.
Phan
Jack
J
Department of Human Genetics, David Geffen School of Medicine and Molecular Biology Institute, University of California, Los Angeles 90073, USA.
Reue
Karen
K
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism; D001835:Body Weight; D002151:Calorimetry; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D009930:Organic Chemicals; D010100:Oxygen / Q000378:metabolism; D010711:Phosphatidate Phosphatase; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000890:Anti-Infective Agents; D009687:Nuclear Proteins; D009930:Organic Chemicals; C088310:lipine; D012313:RNA; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase; D005947:Glucose; D010100:Oxygen