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Effects of Conjugated Linoleic Acid (CLA) on Skeletal Muscle Metabolism

Although it is well known that increased physical activity can help reduce incidences of obesity, physical activity can be influenced by complex issues, making it difficult to use universal means to control obesity. Recent discoveries of the effects of exercise at the cellular level opened up the unique opportunity to develop compounds with ‘exercise-like’ effects. In fact, CLA has been shown to promote voluntary activity and endurance capacity in mice. Thus, the purpose of these studies is to determine the mechanisms of conjugated linoleic acid on muscle metabolism via the modulation of biochemical events including mitochondrial biogenesis and the alternation of fiber composition in skeletal muscle in order to develop preventive strategies for obesity. Based on in vitro fundamental mechanism studies, we observed that CLA stimulated mitochondrial biogenesis by signaling the up-regulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and related biomarkers involved in muscle metabolism. These new findings provided the opportunity to consider CLA as a candidate for bioactive compound mimicking exercises. We conducted additional animal studies, which were organized into three parts. The first part was an adult obesity study with the nescient basic helix loop helix 2 (Nhlh2) gene knockout mice, which are the genetically induced inactivity adult-onset obesity model. Moreover, the study was designed for childhood obesity with post-weaning Nhlh2 mice under the pre-obese state. Lastly, this was an exercise model, which divided normal mice into four groups according to diet and training, such as sedentary or exercise regimes. Consequently, these three studies have shown that CLA enhances voluntary activity and endurance capacity. Additionally, there were increases of muscle mass and decreases of body fat mass through modulating muscle metabolism by stimulating mitochondrial biogenesis, inducing genes of muscle fibers, and enhancing lipid metabolism based on the AMP-activated protein kinase (AMPK) signaling pathway. Particularly, the PPARδ-mediated pathway plays a central role in overall skeletal muscle metabolism. The current results suggest that CLA acts as a potential exercise-mimetic, resulting in improved physical activity, which can also support its function of regulating body fat.