Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Nutrition Science

Committee Chair

Tara M. Henagan

Committee Member 1

Kimberley K. Buhman

Committee Member 2

Kee-Hong Kim

Committee Member 3

Barbara M. Stefanska


Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation and accumulation of fatty acid intermediates in the form of long and medium chain acylcarnitines, may contribute to ectopic lipid deposition and insulin resistance during high fat diet (HFD)-induced obesity. Anterograde and retrograde communication play a role in nucleo-mitochondrial crosstalk that determines skeletal muscle mitochondrial adaptations, specifically alterations in mitochondrial number and function in relation to obesity and insulin resistance. High fat diet (HFD) feeding affects the expression of nuclear-encoded mitochondrial genes (NEMGs) nuclear receptor factor 1 (NRF-1), 2 (NRF-2) and peroxisome proliferator receptor gamma coactivator 1 alpha (PGC-1α) thereby, playing a role in the onset and progression of insulin resistance during obesity. These HFD-induced alterations in NEMG expression affect skeletal muscle mitochondrial adaptations in relation to beta oxidation of fatty acids. Acylcarnitines or fatty acid intermediates resulting from mitochondrial beta oxidation have a potential to act as retrograde signals in nucleo-mitochondrial crosstalk. In contrast to these effects of HFD, many studies have shown that acute exercise upregulates PGC-1α and other NEMGs in association with improvement in insulin sensitivity and beneficial mitochondrial adaptations.