Nutrition and physical activity are environmental factors that play a vital role in health maintenance. Both are part of the first line of obesity treatment. The physiological effects of physical activity have been known for decades; however, it was not until recently that the biochemical and molecular effects started to receive special attention. Uncoupling proteins (UCP) are mitochondrial proteins that produce heat by dissipating the electrochemical potential located in the intermembrane

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... . UCP have shown to protect against reactive oxygen species, lipid peroxidation, free fatty acid accumulation, and insulin resistance, at the same time of increasing metabolic rate. Three isoforms have been detected in humans, UCP-1, UCP-2 and UCP-3, with UCP-3 being the predominant isoform expressed in skeletal muscle. Two transcription factors that have been proposed as important regulators of UCP expression activation are peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1-α) and peroxisome proliferatoractivated receptor alpha (PPARα). Both transcription factors play a central role in the response to external stressors, like fasting and exercise. β-aminoisobutyric acid (BAIBA), a small molecule produced by PGC-1α, is a myokine that has recently been shown to produce browning of white adipose tissue and increased β-oxidation in hepatocytes by acting through PPARα. In vitro, BAIBA treatment has shown to increase mitochondrial respiration and the expression of UCP. The main objective of the present review is to provide a discussion with relevant information regarding various factors that regulate UCP-3 expression in skeletal muscle.