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Ski transgenic mice are resistant to diet-induced obesity and have altered skeletal muscle metabolic gene expression
Transgenic mice over-expressing chicken Ski (c-Ski) develop marked muscle hypertrophy, and decrease in body fat. The underlying mechanisms for the decreased fat mass in the c-Ski mice are unclear. Previous studies in our laboratory suggest that the skeletal muscle expression of the master lipogenic regulator SREBP1c and the nuclear receptor, LXR are suppressed in the Ski mice (Leong GM, et al. Int J Obesity 2010; 34:524—36). Based on these and other findings, we hypothesized that c-Ski mice are resistant to diet-induced obesity. Wild type (WT) and Ski mice were challenged on a high fat (HF) diet from 6 weeks old for 12 weeks, and glucose tolerance testing performed and skeletal muscle nuclear hormone receptor (NR) and metabolic gene expression assessed by qRT-PCR using ABI Taqman Low Density Arrays (TLDAs).
At 18—20 weeks of age, HF-fed WT mice compared to chow-fed WT mice were significantly heavier by 25%. By contrast, body weights of HFand chow-fed Ski mice were not significantly different, despite Ski mice having a lower rate of physical activity and the same amount of food consumption than WT mice. Moreover, in HF-fed Ski mice, the fat pads were significantly smaller and the muscle mass larger than in HF-fed WT littermate controls. Glucose tolerance tests revealed HF-fed Ski mice had unaltered glucose tolerance compared to chow-fed Ski mice, whilst as expected, WT mice on HF-diet compared to chow-fed WT mice had significantly worse glucose tolerance. Analysis of NR and metabolic mRNA gene expression in Ski mice revealed significant changes in several key NR genes and gene pathways involved in glucose and lipid metabolism that in part provide explanation for the body composition and metabolic phenotype of the Ski mice. In conclusion, these studies suggest that c-Ski transgenic mice are resistant to diet-induced obesity and glucose-intolerance and that Ski targets several key NR and metabolic gene pathways to modulate body composition and metabolism.
History
Publication title
Obesity Research & Clinical PracticeVolume
4 (Suppl 1)Pagination
S63ISSN
1871-403XDepartment/School
School of NursingPublisher
ElsevierPlace of publication
United KingdomEvent title
11th International Congress on ObesityEvent Venue
Stockholm, SwedenDate of Event (Start Date)
2010-07-11Date of Event (End Date)
2010-07-15Repository Status
- Restricted