Fat deficiency gene also spu...( A gene earlier found to underlie lipody...)

A gene earlier found to underlie lipodystrophy--a disorder characterized by a severe deficiency of fat--can also spur obesity, according to new research published in the premier issue of Cell Metabolism. The gene, which alters fat storage and metabolism, is the first found to adjust body fat content up or down, depending on its expression level in fat and muscle, according to the researchers.

The gene might therefore represent a novel peripheral target for the treatment of obesity and lipodystrophy, they said. The finding further suggests that differences in lipin might contribute to the natural range of fat levels found among people.

The group, led by Karen Reue of the David Geffen School of Medicine and the University of California, Los Angeles found that excess levels of lipin, in either the fat tissue or skeletal muscle of mice, promote obesity. The protein operates through diverse mechanisms to affect body weight, they show. While lipin in fat influences the storage capacity of fat cells, in muscle the protein determines whole-body energy expenditure and the rate at which the body burns fat.

"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," Reue said. "Lipin represents the first gene with the capacity to go both ways on the scale, modulating body fat content from one extreme to the other."

Lipin is normally found in metabolically active tissues such as fat and skeletal muscle. Mice lacking lipin exhibit lipodystrophy, with symptoms including a severe deficiency of adipose tissue and insulin resistance. A deficiency of lipin prevents both diet-induced and genetic obesity and is required for the normal development of mature fat cells, Reue's team reported last year.

To further elucidate lipin's role, the researchers generated transgenic mice with enhanced expression of the gene
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
18-Jan-2005

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