Lashbrook 2016 Thesis

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Lashbrook M (2016) Functional responses of cardiac and skeletal muscle mitochondria to short-term obesity: are all obesities the same? Master's Thesis 63pp.

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Lashbrook M (2016) Master's Thesis

Abstract: Obesity is associated with metabolic alterations, specifically in the mitochondria, that may play a role in the development of insulin resistance and type 2 diabetes. In nature, there are circumstances where obesity is normal, even favored as seen in mammals that hibernate (hibernators). Understanding the consequences of obesity in ‘hibernators’ versus ‘disease’ models might yield novel insights on the effect of short-term obesity on mitochondrial function. The aim of this study is to compare mitochondrial function in a hibernator, the golden-mantled ground squirrel (Callospermophilus lateralis) and Ob/Ob mice following 4-6 weeks of hyperphagia versus their respective lean controls. Glucose tolerance tests were administered in lean, summer active squirrels (summer); hyperphagic obese, pre-hibernation period squirrels (prehib); and 5-week-old leptin-deficient (ob) and control (WT) C57-BL6J mice prior to sacrifice. High-resolution respirometry was used to examine mitochondrial function in permeabilized solei muscle fibers and isolated cardiac and skeletal muscle mitochondria obtained from all study groups. Body mass of obese animals was 30 and 50% greater than respective lean controls in squirrels and mice, respectively. Glucose intolerance developed with obesity in both species. Skeletal muscle mitochondria exhibited a greater capacity to oxidize pyruvate in the presence of lipids in squirrels, but not in mice. Cardiac oxidative phosphorylation (OXPHOS) capacity significantly increased only in squirrels, and exhibited a significantly greater capacity to oxidize pyruvate in the presence of lipids. No significant change was observed in mice cardiac mitochondria. Mitochondrial responses to obesity differed between models despite nearly identical effects of weight gain and glucose intolerance. Therefore, the observed differences between squirrel and mice likely reflect responses to different environmental cues or genetic background independent of ‘classic’ effects of obesity. The observed mitochondrial responses are not simply responses of obesity and glucose intolerance.


O2k-Network Lab: US CO Fort Collins Chicco AJ


Labels: MiParea: Respiration, Genetic knockout;overexpression, Comparative MiP;environmental MiP  Pathology: Diabetes, Obesity 

Organism: Mouse, Other mammals  Tissue;cell: Heart, Skeletal muscle  Preparation: Permeabilized tissue, Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: F, N, NS  HRR: Oxygraph-2k 

2016-09