Stay lean without dieting: Lose Sam68

Alternative splicing is well known to be tissue-specific. Although several genes have been shown to undergo alternative splicing in adipocytes, little is known about the mechanism that regulates alternative splicing during adipogenesis. We recently reported that Sam68(−/−) mice exhibit a lean phenotype and are protected against diet-induced obesity. Our genome-wide exon array analysis in white adipose tissue (WAT) from wild-type and Sam68(−/−) mice revealed that Sam68 deficiency leads to an abnormal splicing of the mTOR gene. This has been shown to reduce the overall mTOR protein content and activity during in vitro adipose differentiation. In Sam68(−/−) mice, this situation leads to an increased energy expenditure, decreased adipogenesis and WAT formation.