Obesity is an increasingly prevalent morbidity with nearly two thirds of adult Americans overweight, half of whom are obese . Obesity-related health issues have been reported to increase healthcare costs by an estimated $147 billion annually . Over the past decade, chemical and behavioral interventions that favorably modify metabolic rate have been central to obesity research.
Several over-the-counter dietary supplements claim to increase metabolic rate and enhance fatty acid catabolism. Of the available over-the-counter (OTC) dietary supplements, OxyElite Pro (OEP) produced by USP Laboratory and Cellucore Super HD (CHD) are purported to increase metabolic rate and fat metabolism .
OEP has been shown to increase markers of fat mobilization, metabolic rate (measured via indirect calorimetry), and reduce bodyweight and body fat (estimated via Dual-energy X-ray absorptiometry) in healthy young subjects following ingestion [3, 4]. A key ingredient 1,3-dimethylamylamine (also known as germanium, geranamine or DMAA) has been implicated for potential contraindications. DMAA is purported to increase both systolic and diastolic blood pressure in young and healthy men and women immediately following ingestion, although these observations have been inconsistent during longer treatments with OEP in young men [4–7]. DMAA is also purported to cause false-positive results for amphetamines on select immunoassays, a profound implication for athletes with sanctioned governing bodies . CHD, a newer dietary supplement has very limited research regarding safety or efficacy. CHD is advertised to increase metabolic rate and decrease fatty acid synthesis. Many of the ingredients including caffeine have been previously linked to increased metabolic rate. Moreover, because supplements commonly contain a variety of ingredients in proprietary blend forms, and few controlled studies have been performed to address the metabolic effects at the cellular level, further work is needed to identify possible metabolic effects. This work specifically addresses the effects that treatment with OEP or CHD supplements have on metabolism in human skeletal muscle cells.
Peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) is a transcriptional coactivator that is essential for mitochondrial biosynthesis and activates genes that regulate energy homeostasis and metabolism [9–11]. PGC-1α increases fatty acid oxidation through increased peroxisome proliferator-activated receptor alpha (PPARα) expression, which increases forkhead box protein 1 (FOXO1), nuclear respiratory factors 1 and 2 (NRF1/2) and other factors influencing fat oxidation [12–14]. PGC-1α is also an important signaling molecule in the activation and regulation of gluconeogenesis, which is likely mediated through FOXO1 and estrogen-related receptor alpha (ERR-α) [12, 15–18]. Thus, PGC-1α modifies metabolic rate and expression of genes involved in gluconeogenesis, fat oxidation and mitochondrial biosynthesis [12–18].
Clinically, the relationship between low PGC-1α expression and type II diabetes/obesity has been identified [19–22]. Low PGC-1α is also associated with reduced expression of oxidative phosphorylation genes, decreasing fatty acid oxidation and energy utilization [19, 23, 24]. Treatment with the PGC-1α stimulator Rosiglitazone (through binding and activating PPARγ) increased mitochondrial density and function, while improving insulin sensitivity . Further evidence suggests that an increase in PGC-1α (independent of Rosiglitazone) can improve insulin sensitivity and improve muscle function . It has also been identified that PGC-1α is essential for the recovery from the diminished ATP caused by chemical uncoupling as evidenced by the lack of recovery in PGC-1α null cells and animals .
Treatment with potent research-grade chemicals such as 2,4-dinitrophenol (DNP) and p-trifluromethoxy phenylhydrazone (FCCP) have been shown to induce PGC-1α in fibroblasts . Moreover, our laboratory recently identified that treatment with DNP or caffeine can induce PGC-1α, and increase both metabolic rate and mitochondrial content in muscle cells suggesting that commercially available metabolic stimulators might have similar effects . The well documented effects of PGC-1α on metabolism suggest that modulation of PGC-1α expression is a potential strategy for altering metabolic rate.
Purpose- This work seeks to explore effects of treatment with OTC dietary supplements on mitochondrial and glycolytic metabolism in skeletal muscle cells. Human rhabdomyosarcoma cells are a naturally immortalized cell model, frequently used for making inferences about muscle tissue adaptations [27–31]. We show that treatment of muscle cells with OEP or CHD at varied doses induce PGC-1α mRNA and protein in a dose and time sensitive manner. We also illustrate that treatment with either OEP or CHD increase mitochondrial content. This work identifies for the first time the effects that several OTC diet supplements have on mitochondria content and cell metabolism in muscle cells.