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Endocrine Abstracts (2009) 20 HTB4

ECE2009 Basic Highlights Hot topics: Basic (5 abstracts)

Mice deficient for the Sam68 RNA binding protein are protected from dietary obesity and insulin resistance

Gillian Vogel & Stephane Richard


Lady Davis Institute, McGill University, Montreal, Quebec, Canada.


The Src substrate associated in mitosis of 68 kDa (Sam68) is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism. The tyrosine phosphorylation of Sam68 was shown to negatively regulate its RNA binding activity and hence it was termed a Signal Transduction Activator of RNA (STAR) protein. Although KH-type RNA binding domains are known to mediate specific protein-RNA interactions, their RNA targets remain elusive. Nevertheless, Sam68 has been shown to regulate HIV Rev nuclear export pathway, the constitutive transport element and alternative splicing. To define the physiological role of this RNA binding protein, we generated Sam68 deficient mice (Richard et al. 2005, PLOS Genetic 1:e74). Previously we reported that the Sam68 deficient mice were protected from age-induced bone loss (Richard et al. 2005, PLOS Genetic 1:e74) and delayed breast tumorigenesis (Richard et al. 2008 Oncogene 27:548). Here we report that homozygote Sam68−/− mice have a lower body and adipose tissue weight despite normal insulin sensitivity. These mice are protected against dietary obesity owing to deregulation in lipid metabolism associated with adipogenesis defects. Moreover, they remain insulin sensitive when placed on high-fat diet. We observed that the expression of peroxisome proliferator-activated receptor-γ (PPARγ) is reduced in Sam68−/− mice. Consistent with these results, differentiation ability of 3T3-1L preadipocyte cells depleted of Sam68 is attenuated for adipocyte differentiation. These results suggest that the Sam68 RNA binding protein is a novel regulator of adipogenesis and represents a new target to treat type II diabetes and obesity.

This work was funded by grant MT-13377 from the Canadian Institutes of Health Research (CIHR) to S.R who is an investigator of the CIHR.

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