Treatment of human muscle cells with popular dietary supplements increase mitochondrial function and metabolic rate

Nutrition & Metabolism

Carole A Conn²  Kristina Trujillo¹  Marco Bisoffi¹  Miguel A Barberena¹  Randi Garcia-Smith¹  Roger A Vaughan² 

[1] Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA;Department of IFCE: Nutrition, University of New Mexico, Albuquerque, NM, 87131, USA

关键词: Dietary supplements;    Oxidative phosphorylation;    Metabolic syndrome;    Extracellular acidification and oxygen consumption rates;    PGC;    Mitochondrial biosynthesis;   

Others  :  811768
DOI  :  10.1186/1743-7075-9-101

 received in 2012-07-11, accepted in 2012-11-07,  发布年份 2012

【 摘 要 】

Background

Obesity is a common pathology with increasing incidence, and is associated with increased mortality and healthcare costs. Several treatment options for obesity are currently available ranging from behavioral modifications to pharmaceutical agents. Many popular dietary supplements claim to enhance weight loss by acting as metabolic stimulators, however direct tests of their effect on metabolism have not been performed.

Purpose

This work identified the effects popular dietary supplements on metabolic rate and mitochondrial biosynthesis in human skeletal muscle cells.

Methods

Human rhabdomyosarcoma cells were treated with popular dietary supplements at varied doses for 24 hours. Peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α), an important stimulator of mitochondrial biosynthesis, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was measured using flow cytometry confirmed with confocal microscopy. Glycolytic metabolism was quantified by measuring extracellular acidification rate (ECAR) and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR). Total relative metabolism was quantified using WST-1 end point assay.

Results

Treatment of human rhabdomyosarcoma cells with dietary supplements OxyElite Pro (OEP) or Cellucore HD (CHD) induced PGC-1α leading to significantly increased mitochondrial content. Glycolytic and oxidative capacities were also significantly increased following treatment with OEP or CHD.

Conclusion

This is the first work to identify metabolic adaptations in muscle cells following treatment with popular dietary supplements including enhanced mitochondrial biosynthesis, and glycolytic, oxidative and total metabolism.

【 授权许可】

   
2012 Vaughan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Flegal KM, Carroll MD, Ogden CL, Johnson CL: Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002, 288:1723-1727.
• [2]Study estimates medical cost of obesity May Be as high as $147 billion annually. http://www.cdc.gov/media/pressrel/2009/r090727.htm webcite.
• [3]McCarthy CG, Farney TM, Canale RE, Alleman RJ Jr, Bloomer RJ: A finished dietary supplement stimulates lipolysis and metabolic rate in young Men and women. Nutrition and Metabolic Insights 2011, 5:23.
• [4]McCarthy CG, Canale RE, Bloomer RJ, Alleman RJ Jr: Biochemical and anthropometric effects of a weight loss dietary supplement in healthy Men and women. Nutr Metab Insights 2011, 5:13.
• [5]Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE: Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy Men and women. Phys Sportsmed 2011, 39:111-120.
• [6]Whitehead PN, Schilling BK, Farney TM, Bloomer RJ: Impact of a dietary supplement containing 1,3-dimethylamylamine on blood pressure and bloodborne markers of health: a 10-week intervention study. Nutr Metab Insights 2012, 5:33.
• [7]Farney TM, McCarthy CG, Canale RE, Alleman RJ Jr, Bloomer RJ: Hemodynamic and hematologic profile of healthy adults ingesting dietary supplements containing 1,3-dimethylamylamine and caffeine. Nutr Metab Insights 2011, 5:1.
• [8]Vorce SP, Holler JM, Cawrse BM, Magluilo J Jr: Dimethylamylamine: a drug causing positive immunoassay results for amphetamines. J Anal Toxicol 2011, 35:183-187.
• [9]Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, Williams RS: Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 2002, 296:349-352.
• [10]Esterbauer H, Oberkofler H, Krempler F, Patsch W: Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics 1999, 62:98-102.
• [11]Knutti D, Kaul A, Kralli A: A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen. Mol Cell Biol 2000, 20:2411-2422.
• [12]Yoon JC, Puigserver P, Chen GX, Donovan J, Wu ZD, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, et al.: Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 2001, 413:131-138.
• [13]Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong HJ, Accili D, Spiegelman BM: Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1 alpha interaction. Nature 2003, 423:550-555.
• [14]Vega RB, Huss JM, Kelly DP: The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 2000, 20:1868-1876.
• [15]Herzig S, Long FX, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, et al.: CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 (vol 413, pg 179, 2001). Nature 2001, 413:652-652.
• [16]Rhee J, Ge HF, Yang WL, Fan M, Handschin C, Cooper M, Lin JD, Li C, Spiegelman BM: Partnership of PGC-1 alpha and HNF4 alpha in the regulation of lipoprotein metabolism. J Biol Chem 2006, 281:14683-14690.
• [17]Alaynick WA: Nuclear receptors, mitochondria and lipid metabolism. Mitochondrion 2008, 8:329-337.
• [18]Shao D, Liu Y, Liu X, Zhu L, Cui Y, Cui A, Qiao A, Kong X, Liu Y, Chen Q, et al.: PGC-1 beta-Regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha. Mitochondrion 2010, 10:516-527.
• [19]Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, et al.: Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 2003, 100:8466-8471.
• [20]Semple RK, Crowley VC, Sewter CP, Laudes M, Christodoulides C, Considine RV, Vidal-Puig A, O'Rahilly S: Expression of the thermogenic nuclear hormone receptor coactivator PGC-1 alpha is reduced in the adipose tissue of morbidly obese subjects. Int J Obes 2004, 28:176-179.
• [21]Yang XL, Enerback S, Smith U: Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance. Obes Res 2003, 11:1182-1191.
• [22]Chowdhury SKR, Dobrowsky RT, Femyhough P: Nutrient excess and altered mitochondrial proteome and function contribute to neurodegeneration in diabetes. Mitochondrion 2011, 11:845-854.
• [23]Mootha VK, Handschin C, Arlow D, Xie XH, Sihag S, Yang WL, Altshuler D, Puigserver P, Patterson N, St Pierre J, et al.: Err alpha and Gabpa/b specify PGC-1 alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle (vol 101, pg 6570, 2004). Proc Natl Acad Sci USA 2005, 102:10405-10405.
• [24]Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A: The estrogen-related receptor alpha (ERR alpha) functions in PPAR gamma coactivator 1 alpha (PGC-1 alpha)-induced mitochondrial biogenesis. Proc Natl Acad Sci USA 2004, 101:6472-6477.
• [25]Benton CR, Bonen A: PGC-1alpha expression correlates with skeletal muscle fibre type and fuel handling proteins. FASEB J 2005, 19:A1121-A1121.
• [26]Rohas LM, St-Pierre J, Uldry M, Jager S, Handschin C, Spiegelman BM: A fundamental system of cellular energy homeostasis regulated by PGC-1 alpha. Proc Natl Acad Sci USA 2007, 104:7933-7938.
• [27]Vaughan RA, Garcia-Smith R, Bisoffi M, Trujillo KA, Conn CA: Effects of caffeine on metabolism and mitochondria biogenesis in rhabdomyosarcoma cells compared with 2,4-dinitrophenol. Nutr Metab Insights 2012, 5:59.
• [28]Carrasco MA, Muller M, Cardenas C, Quest A, Behrens MI, Jaimovich E: Role of calcium and PKC in CREB phosphorylation induced by depolarization in skeletal muscle cells in culture. Soc Neurosci Abstr 2001, 27:1296.
• [29]Armoni M, Quon MJ, Maor G, Avigad S, Shapiro DN, Harel C, Esposito D, Goshen Y, Yaniv I, Karnieli E: PAX3/Forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. J Clin Endocrinol Metabol 2002, 87:5312-5324.
• [30]Araki M, Maeda M, Motojima K: Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate. Eur J Pharmacol 2012, 674:95-103.
• [31]Singh P, Kohr D, Kaps M, Blaes F: Skeletal muscle MHC I expression: implications for statin-induced myopathy. Muscle Nerve 2010, 41:179-184.
• [32]Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001, 29:e45.
• [33]Wikstrom JD, Sereda SB, Stiles L, Elorza A, Allister EM, Neilson A, Ferrick DA, Wheeler MB, Shirihai OS: A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets. PLoS One 2012, 7:e33023.
• [34]Giulivi C, Ross-Inta C, Horton AA, Luckhart S: Metabolic pathways in anopheles stephensi mitochondria. Biochem J 2008, 415:309-316.
• [35]Vaughan RA, Garcia-Smith R, Bisoffi M, Conn CA, Trujillo KA: Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells. Lipids Health Dis 2012, 11:142. BioMed Central Full Text
• [36]Huang C, Somwar R, Patel N, Niu WY, Torok D, Klip A: Sustained exposure of L6 myotubes to high glucose and insulin decreases insulin-stimulated GLUT4 translocation but upregulates GLUT4 activity. Diabetes 2002, 51:2090-2098.