Diaz, M and Martel, N and Myers, SA and Fitzsimmons, R and Pearen, M and Muscat, GEO and Leong, GM, Ski transgenic mice are resistant to diet-induced obesity and have altered skeletal muscle metabolic gene expression, Obesity Research & Clinical Practice, 11-15 July, 2010, Stockholm, Sweden, pp. S63. ISSN 1871-403X (2010) [Conference Extract]
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.
|Item Type:||Conference Extract|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and Cell Biology|
|Research Field:||Cell Metabolism|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Author:||Myers, SA (Dr Stephen Myers)|
|Deposited By:||Health Sciences B|
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