Obesity in men is caused by genes that have been discovered by scientists.
A genome-wide linkage scan for high body mass index (BMI) in 3,893 men and 4,445 women has identified a link on chromosome 5q13-15.
Analysis of this chromosome has revealed a rare cluster of gene types linked to high BMI in men but not women. The portion of the chromosome related to high BMI risk contains a single gene named "arrestin domain containing 3" (Arrdc3).
Researchers investigated Arrdc3 expression and detected it in human fat and muscle. Analysis of gene expression in human abdominal fat biopsies showed significant correlation of Arrdc3 messenger RNA with BMI in men but not women, supporting the male-specific linkage to obesity.
The study also found that fasting increased Arrdc3 expression in both human and mouse fat tissue, suggesting that Arrdc3 functions to conserve energy when food is not available.
To test whether the gene casually regulates obesity, the scientist generated a mouse without Arrdc3. The mice without Arrdc3 showed a "striking resistance" to age-induced obesity: the mice without Arrdc3 had a smaller total body mass compared to mice with the gene.
And consistent with human data, loss of Arrdc3 had less effect on female mice. The Arrdc3-null mice were also resistant to metabolic complications of obesity - having a strong response to insulin, faster clearance of glucose and lower lipids.
"These results implicate a novel family of arrestins in the control of metabolism and development of obesity," said researchers.