This Is AuburnElectronic Theses and Dissertations

Exploring the Impact of Obesity, Type 2 Diabetes Mellitus, Nerve Growth Factor, and Exercise on Skeletal Muscle




Jun, Lauren

Type of Degree

PhD Dissertation


Nutrition, Dietetics and Hospitality Management

Restriction Status


Restriction Type


Date Available



Skeletal muscle is the largest organ of the body with many essential functions. Recent studies have linked obesity and type 2 diabetes mellitus (T2DM) with skeletal muscle loss and dysfunction. The first objective of this study was to investigate the effects of obesity, T2DM, and nerve growth factor (NGF) on skeletal muscle atrophy markers. Examination of several molecular pathways associated with muscle atrophy revealed increased levels of atrophy markers in obese and T2DM model. Moreover, NGF was shown to mitigate these levels through inhibition of myostatin cleavage and subsequent translocation of FoxO1 transcription factor. Obesity has been shown to affect skeletal muscle fiber type proportions, reducing overall oxidative capacity, which fuels the development of insulin resistance in skeletal muscle. Thus, the second part of the dissertation work aimed to investigate mitochondrial markers in the skeletal muscle of obese and T2DM mouse model. Although there was no significant difference in the mitochondrial markers of both obese and T2DM model, NGF treatment was shown to elevate the markers associated with mitochondrial biogenesis and fusion, highlighting potential effects of NGF in alleviating dysfunctional mitochondria often associated with metabolic diseases. Moderate-intensity exercise has been recognized to increase the content and quality of mitochondria in skeletal muscle. This third part of the dissertation work revealed reduced mitochondrial markers in the muscle of obese mouse model, which were effectively elevated in the exercised obese counterparts. The increase in mitochondrial markers was shown to be associated with enhanced mitochondrial biogenesis and fission.