Oral Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

Physiological testing reveals impaired muscle function in obese mice (#134)

Joseph Power 1 , Susan McLennan 1 2 , Marco Morsch 1 , Tania Markovic 2 3 , Christine Yee 1 , Stephen Twigg 1 2 , Charmaine Tam 1 3 4
  1. Sydney Medical School , The University of Sydney, Sydney, NSW, Australia
  2. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. The Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, The University of Sydney, Sydney, NSW, Australia
  4. Charles Perkins Centre and School of Biological Sciences, The University of Sydney, Sydney, NSW, Australia

Investigating changes in skeletal muscle, particularly functional changes that occur with obesity and diabetes are critical to elucidating the pathophysiology and associated complications of these diseases. The aims of this study were to determine if diet-induced obesity and subsequent diabetes induction causes impairments in muscle function and the molecular mechanisms of these effects. Male C57BL/6 mice were fed standard chow (CHOW) (n=20) or 45%fat diet (HFD) (n=25) for 15 weeks. Three non-invasive muscle function tests were then administered: Hang mesh (best time), hang wire (best time), and forelimb grip strength (peak force). From the hang wire test, we calculated an aggregate score [(10- number of falls)+ number of reaches (reached end of the wire)+1)*time]. Hang mesh and hang wire score were multiplied by body weight. Normal and not-normally distributed data are presented as mean±SD and median(interquartile range).

At 15 weeks, HFD mice had gained significantly more weight (HFD= ∆17.5±12.5g; CHOW= ∆8.0±2.5g; P<0.001) and had higher blood glucose (HFD=8.0±1.2; CHOW=6.7±1.3mmol/L; P=0.03) compared to CHOW. After adjustment for body weight, HFD mice performed significantly worse in hang mesh (HFD=3130 (2562–4093); CHOW= 4950 (3575–5616) seconds*gram; P=0.004) and hang wire tests (HFD=3198 (2381–5365); CHOW= 37523 (11156–72833); P<0.001) compared to CHOW. There was no group difference in grip strength.

These data represent the first results from an animal model examining obesity and diabetes-related muscle dysfunction. Even after adjustment for body weight, we observed a significant decline in muscle function with weight gain, suggesting that obesity is associated with impaired muscle function in mice. In ongoing analyses, we will induce diabetes (STZ injection) in a subset of these mice. At 25 weeks, muscle function tests will be repeated and muscle tissues harvested to examine molecular pathways (extracellular matrix proteins, dystrophin-associated protein complex) potentially associated with impaired muscle function.