Thesis Defence: Comparing Monocyte and Skeletal Muscle Mitochondrial Metabolism in Individuals That Are Lean or Living With Obesity – A Cross-Sectional Study

Spencer Ursel, supervised by Dr. Jonathan Little, will defend their thesis titled “Comparing Monocyte and Skeletal Muscle Mitochondrial Metabolism in Individuals That Are Lean or Living With Obesity – A Cross-Sectional Study” in partial fulfillment of the requirements for the degree of Master of Science in Health and Exercise Sciences.

An abstract for Spencer Ursel’s thesis is included below.

Defences are open to all members of the campus community as well as the general public. Registration is not required for in-person defences.

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Abstract

Obesity is a major risk factor for type 2 diabetes (T2D), in part due to its association with chronic low-grade inflammation and insulin resistance. Monocytes represent an important immune cell subset implicated in obesity-related inflammation. Evidence suggests that monocyte phenotype is related to their metabolic profile, however monocyte metabolism in obesity remains poorly characterized. Second, mitochondrial dysfunction is commonly exhibited during obesity and type 2 diabetes, however, these studies often do not account for activity levels, which have been shown to greatly impact mitochondrial function. Therefore, this study aimed to compare mitochondrial respiration in circulating monocytes and vastus lateralis skeletal muscle between lean individuals and those living with obesity, while matching participants for habitual activity levels.

In a cross-sectional study design, 37 healthy adults (lean: n=20; obesity: n=17) – matched for physical activity, age, and sex distribution – completed two experimental visits involving a skeletal muscle biopsy, serial blood sampling throughout a mixed meal tolerance test (MMTT), and accelerometer-based physical activity tracking. Mitochondrial respiration was assessed using high-resolution respirometry in monocytes isolated from fasted blood samples and in permeabilized skeletal muscle fibres from the vastus lateralis biopsy.

We found that monocyte respiration was significantly higher in lean individuals for CI+II oxidative phosphorylation (OXPHOS) and maximal uncoupled respiration (p < 0.05), suggesting diminished respiratory capacity in monocytes from individuals with obesity. Opposingly, we found that skeletal muscle respiration was significantly higher in the group living with obesity across all respiratory states (p < 0.05). Activity levels were similar between groups, suggesting results were not confounded by habitual physical activity.

These findings highlight distinct, tissue-specific alterations in mitochondrial metabolism in young individuals with obesity compared to lean counterparts. We hypothesize that the reduction in monocyte respiration may reflect systemic impairments in mitochondrial function, while increased skeletal muscle respiration may represent an early compensatory mechanism to energy surplus and lipid oversupply.