Insufficient physical activity is a global health problem and as per recent literature, approximately one-third of the world's adult population fails to achieve recommended levels of physical activity. An underappreciated primary cause of most chronic conditions is the lack of sufficient daily physical activity. Overwhelming evidence proves the notion that reductions in daily physical activity is primary causes of chronic diseases/conditions and also that exercise is rehabilitative therapy from the inactivity-caused dysfunctions.

There are several underlying mechanisms responsible for exercise-induced benefits such as, organ-to-organ crosstalk that contributes to metabolic homeostasis and affects the inflammatory response related pathways and fibrotic changes. Some of the best recognized beneficial effects of exercise on muscles are mediated by the transcriptional factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Skeletal muscles are highly vascularized tissue and have secretory abilities. Not only muscles release amino acids for fulfilling increased energy demand and to fuel the liver for undergoing gluconeogenesis, but also proteins to mediate inter-tissue crosstalk. Robust research have identified numerous endogenous factors secreted by myocytes (muscle cells) known as myokines or "exercise factor" upon regular exercise via PGC-1α-dependent mechanism. It has been reported that the levels of these myokines are upregulated during aerobic physical exercise.

Amino acid, a novel non-protein amino acid secreted by skeletal muscles which aids the cross-talk between skeletal muscles, liver, and adipose tissue at molecular levels. amino acid is generated by catabolism of the branched-chain amino acid valine. Existing literature states, amino acid induces body fat loss by increasing energy expenditure, stimulating free fatty acid (FFA) oxidation in the liver and skeletal muscle cell, and by enhancing oxygen consumption by adipose tissue and hepatocytes. It was observed that amino acid stimulated differentiation of energy storing white adipose tissue preadipocytes to an energy burning "beige" (brown to white) phenotype. Uptake of plasma nutrients such as glucose, triglycerides (TG)-rich very low-density lipoproteins (VLDL), and FFA by cold-activated brown adipose tissue might be responsible for modulatory effect of amino acid on lipid and glucose metabolism. It is believed that amino acid also exerts its metabolic effects by modulating other circulating signaling molecules such as leptin. amino acid affects lipid metabolism and insulin sensitivity via restoring leptin levels in individuals with leptin deficiency. As about 5-10% of the obese population are low leptin secretor, amino acid might be an ideal intervention for fat loss in such population. It has also been demonstrated that amino acid supplementation activates several "thermogenic programs" similar to those activated by physical exercise. Furthermore, amino acid has been also shown to protect the osteocytes from ROS-induced apoptosis through the MRGPRD and by also maintaining mitochondria integrity. This protective capacity decreases with age as to the down regulation of Mrgprd expression in osteocytes.