The Influence of a High Fat Diet on Mice with and without Myosin Light Chain Kinase: Implications for Muscle Thermogenesis and Obesity
|Work performed at the cellular level suggests that skeletal myosin light chain kinase (skMLCK) mediated phosphorylation of myosin participates in the regulation of muscle thermogenesis. The purpose of this study was to investigate the effect of skMLCK ablation, and resultant loss of myosin phosphorylation, on murine physiology and metabolism. To this end, we compared the morphology and metabolic rate of wildtype and skMLCK absent mice (skMLCK-/- ) in response to 10 weeks of high fat feeding. A larger metabolic challenge better tests the hypothesis that the ability to phosphorylate myosin RLC will aid wildtype mice (WT) in counteracting the obesogenic effects of a HFD more effectively than skMLCK-/- mice. Adult mice (8-12 weeks) of both genotypes were housed at 30°C (thermoneutrality) and randomly assigned to either a control or high fat feeding group (n = 8 per genotype, total of 32 mice). All mice were weighed twice weekly while dual-energy X-ray absorptiometry (DXA) was used at baseline and at week 10 to detect changes in fat and fat-free mass. Metabolic measures such as kcal output as well as behavioural measures such as locomotion, fine movement and food intake were assessed biweekly. At the conclusion of the study, all mice were euthanized, and epididymal white adipose tissue, inguinal white adipose tissue and brown adipose tissue were removed and weighed. Based on cellular studies, it was expected that the absence of myosin phosphorylation would render the skMLCK-/- genotype more susceptible to weight gain than the WT genotype. Contrary to our hypothesis, in vitro data did not translate to effects on whole-body metabolism. WT mice were similarly susceptible to the same morphological and metabolic changes as the skMLCK-/- group when exposed to a high fat diet. Both genotypes consumed the same amount, however, the skMLCK-/- mice were less active and yet, both genotypes gained the same amount of weight. This may suggest a compensatory thermogenic pathway may be at play.
|Skeletal Muscle Thermogenesis, Obesity, skeletal muscle myosin kinase, brown adipose tissue
|The Influence of a High Fat Diet on Mice with and without Myosin Light Chain Kinase: Implications for Muscle Thermogenesis and Obesity
|Electronic Thesis or Dissertation
|M.A. Applied Health Sciences
|Applied Health Sciences Program
|Faculty of Applied Health Sciences