Health Effects of Weight-Loading in Obesity

Abstract

Obesity is increasingly recognized as a disorder of body composition rather than of body weight alone. Modern sedentary living has reduced the habitual mechanical loading of the skeleton compared with the weight-bearing conditions under which human physiology evolved. This transition is thought to promote fat mass accumulation and reduced relative lean mass. Current pharmacological and surgical treatments effectively reduce adiposity but also reduce lean mass, highlighting the need for complementary strategies that improve body composition while preserving skeletal muscle. Increased mechanical weight-loading may influence body composition independently of conventional alterations in whole-body energy balance. The aim of this thesis was to determine whether increased weight-loading improves body composition in adults with obesity and to characterize the associated metabolic, autonomic, and physiological responses. Four complementary studies were performed. A randomized controlled trial evaluated five weeks of externally applied loading with weighted vests in adults with class I obesity (Paper I), with a pre-specified sub-study of cardiovascular and autonomic responses assessed by ambulatory heart rate variability (Paper II). A crossover study used quantitative positron emission tomography/computed tomography (PET/CT) to investigate tissue-specific glucose uptake during acute loading (Paper III), and a controlled preclinical study in diet-induced obese rats examined whether loading-induced changes in body mass iv could be explained by alterations in sodium and water balance (Paper IV). Increased loading shifted body composition in a favorable direction, with lower fat mass and waist circumference and higher lean mass, thereby improving the balance between the two compartments without altering total body weight. Fat loss was concentrated in weight-bearing regions rather than uniformly distributed. The changes occurred despite increased sedentary time and without detectable changes in total energy expenditure or self-reported energy intake. During acute loading, glucose uptake increased selectively in skeletal muscle, cortical bone, and bone marrow of the weight-bearing lower extremities, consistent with localized metabolic activation in loaded tissues. Weight-loading imposed a greater cardiovascular demand during vest use and was accompanied by short-lived reductions in cardiac autonomic modulation, particularly among women, with no evidence of lasting changes in resting autonomic function. In rats, loading reduced body weight gain without affecting sodium or water balance, arguing against fluid redistribution as an explanation for the compositional changes. In conclusion, increased weight-loading improves body composition in adults with obesity by reducing fat mass while increasing lean mass. The effects were localized to loaded tissues, were not explained by measurable changes in whole-body energy expenditure or fluid balance and were accompanied only by transient autonomic responses during active loading. Weight-loading thus emerges as a biologically relevant physiological stimulus influencing body composition and a potential complement to current obesity therapies. How this mechanical signal is sensed and translated into changes in body composition remains an important question for future research.