Conjugated linoleic acid (CLA) influences muscle metabolism via stimulating mitochondrial biogenesis signaling in adult‐onset inactivity induced obese mice

Abstract

Recently, conjugated linoleic acid (CLA) has been reported to prevent body weight gain and fat accumulation in part by improving physical activity in mice. The current study was conducted to determine the role of CLA on skeletal muscle metabolism in nescient basic helix-loop-helix 2 knockout (N2KO) mice, an adult-onset inactivity induced obese model. Five-week-old female N2KO and wild type mice were fed either control or CLA containing diet (0.5%) for 10 wk. Voluntary activity was determined biweekly and markers for muscle metabolisms were determined from the gastrocnemius muscle. CLA fed N2KO animals showed significant increased voluntary movement and gastrocnemius muscle mass compared to control group, whereas in wild type animals, no differences were observed. CLA treatment up-regulated AMP-activated protein kinase (AMPK), mitochondria biogenic markers, peroxisome proliferator-activated receptor-d (PPARd), and mitochondrial transcription factor A (Tfam) compared to control animals. These observations indicate that CLA supplementation activates AMPKa-PPARd and/or -Tfam signaling cascade for stimulating mitochondria biogenesis. Taken together, these results suggest that CLA may in part activate the underlying biomarkers involved in muscle metabolism via stimulation of mitochondrial biogenesis, resulting in increased voluntary activity and muscle mass, potentially contributing to regulating weight gain.Practical applications: Lack of physical activity is a global public health problem, which induces obesity and its associated pathologies. Approximately, 3.2 million deaths per year are attributable to lack of physical activity. CLA has previously been reported to increase voluntary and endurance activities in mice. However, the exact mode of action is not completely understood. Thus, the purpose of the study was to shed light on positive effects of CLA on physical activity through modulation of molecular targets in skeletal muscle of Nhlh2 knockout mice, which are an adult-onset inactivity induced obesity model. The current results suggest that CLA acts as a potential exercise-mimetic, resulting in increased voluntary activity and muscle mass, potentially contributing to regulating weight gain.

Conjugated linoleic acid (CLA) promotes endurance capacity via peroxisome proliferator-activated receptor δ-mediated mechanism in mice

“…In the current study, CLA supplementation facilitated PGC-1α, PPARδ and PGC-1α-NRF-1-Tfam signaling cascades, implying that CLA may have potentiated mitochondrial biogenesis. This observation is consistent with the previous study where CLA isomers induced mitochondrial biogenesis via modulating the same signaling pathway [8,9].…”

“…Earlier studies reported that 0.5% CLA supplemented mice increased voluntary movement (non-exercise physical activity) [7,8,19,20]. However, we did not observe an overall CLA effect on voluntary movement, consistent with a previous publication with exercise [6].…”

“…Meanwhile, there was significant effect of CLA on SIRT1 regardless of exercise. Previously we reported that CLA treatment activated AMPK and PGC-1α independent of SIRT1in C2C12 myotubes and female mice [8,9], whereas CLA supplementation upregulated all AMPK, SIRT1 and PGC-1α in wild type male animals [19]. This discrepancy might be due to the different experimental methods such as in in vitro vs. in vivo, males and females, or duration of CLA supplementation in animal models.…”

“…Although most studies of CLA's antiobesity effects have focused on body fat reduction, accumulated evidence demonstrated that CLA increased lean body mass and enhanced exercise performances [3][4][5]. In fact, the previous studies in rodents have reported that CLA improved voluntary activity and endurance capacity accompanied with modulation of carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor δ (PPARδ) in skeletal muscle [6][7][8].…”

Dose response of rumen‐protected conjugated linoleic acid supplementation to fattening bulls and heifers on growth, and carcass and meat quality

“…Park et al, () and Pariza et al, () noted that reductions in body fat in model animals appeared to be mainly due to lower body fat accretion induced by CLA. This effect was explained by the increased energy expenditure and physical activity of the CLA‐treated subjects (Kim, Kim, Good, & Park, ). Pariza et al, () also suggested that muscle mass may be preserved or enhanced as a consequence of CLA‐induced changes in the profile of cytokines affecting skeletal muscle catabolism and immune function.…”