The efficacy of voluntary exercise and branched chain amino acids in preventing obesity-induced pathological changes in brain and behavior

Abstract

Obesity poses substantial societal risks, affecting public health and threatening the economy. Importantly, obesity-induced changes as found in the periphery also extend to brain structure and function, promoting premature cognitive dysfunction. Voluntary exercise and dietary supplements such as branched chain amino acids (BCAA) each demonstrate promising treatment opportunities. Following a longitudinal paradigm, the preventative effect of voluntary exercise in combination with BCAA against obesity-related changes in brain structure and function is investigated using male diet-induced obese (Ldlr-/-.Leiden) mice. Measurements included physiological parameters and a battery of behavioral tests to investigate cognition and motor skill. In addition, a neuroimaging protocol was performed to assess structural and functional brain connectivity (rs-fMRI and ASL). Individual locomotion and running wheel activity was measured using a digital ventilated cages system. Results demonstrated increased body weight in all animals in response to high fat (+BCAA) diet. While running activity decreased over time, we found that animals on BCAA preserved running endurance during nighttime. However, obesity-related motor impairments could not be prevented by exercise and BCAA supplementation. Moreover, functional MRI was not influenced by exercise and BCAA supplementation, however, exercise normalized CBF under normal conditions relative to baseline. Overall, this study demonstrated that exercise has beneficial effects on obesity-induced pathological changes in brain and behavior, while the synergistic effect of exercise and BCAA remains unseen in early disease state. Keywords: Exercise, Branched chain amino acids, Obesity, Cognition, Animal model, MRI