Abstract
Objectives:
The involvement of skeletal muscle mitochondrial uncoupling protein-3 (UCP3) in the control of energy expenditure in skeletal muscle and at the whole-body level is still a matter of debate. We previously reported that UCP3 downregulation is linked to an enhanced mitochondrial energy metabolism in rat skeletal muscle as a result of acute capsiate treatment. Here, we aimed at investigating noninvasively the effects of chronic capsiate ingestion on metabolic changes occurring in exercising gastrocnemius muscle and at the whole-body level.
Methods:
We used an original experimental setup allowing a complete noninvasive investigation of gastrocnemius muscle function in situ using 31-phosphorus magnetic resonance spectroscopy. Whole-body fat composition was determined using magnetic resonance imaging and UCP3 gene expression was measured by quantitative real-time RT-PCR analysis.
Results:
We found that a 14-day daily administration of capsiate (100 mg kg−1 body weight) reduced UCP3 gene expression and increased phosphocreatine level at baseline and during the stimulation period in gastrocnemius muscle. During muscle stimulation, pHi showed a larger alkalosis in the capsiate group suggesting a lower glycolysis and a compensatory higher aerobic contribution to ATP production. Although the capsiate-treated rats were hyperphagic as compared to control animals, they showed a lower weight gain coupled to a decreased abdominal fat content.
Conclusion:
Overall, our data indicated that capsiate administration contributes to the enhancement of aerobic ATP production and the reduction of body fat content coupled to a UCP3 gene downregulation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB . UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun 1997; 235: 79–82.
Schrauwen P, Hesselink M . Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited. Proc Nutr Soc 2003; 62: 635–643.
Brand MD, Esteves TC. Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2005; 2: 85–93.
Schrauwen P, Hoeks J, Schaart E, Kornips B, Binas B, Van De Vusse GJ et al. Uncoupling protein 3 as a mitochondrial fatty acid anion exporter. FASEB J 2003; 17: 2272–2274.
Faraut B, Giannesini B, Matarazzo V, Marqueste T, Dalamasso C, Rougon G et al. Downregulation of uncoupling protein-3 is linked to changes in muscle mitochondrial energy metabolism in vivo as a result of capsiate administration. Am J Physiol Endocrinol Metab 2007; 292: E1474–E1482.
Ohnuki K, Niwa S, Maeda S, Inoue N, Yazawa S, Fushiki T et al. CH-19 sweet, a non-pungent cultivar of red pepper, increased body temperature and oxygen consumption in humans. Biosci Biotechnol Biochem 2001; 65: 2033–2036.
Giannesini B, Izquierdo M, Le Fur Y, Cozzone PJ, Fingerle J, Himber J et al. New experimental setup for studying strictly noninvasively skeletal muscle function in rat using 1H-magnetic resonance (MR) imaging and 31P-MR spectroscopy. Magn Reson Med 2005; 54: 1058–1064.
Kobata K, Kawaguchi M, Watanabe T . Enzymatic synthesis of a capsinoid by the acylation of vanillyl alcohol with fatty acid derivatives catalyzed by lipases. Biosci Biotechnol Biochem 2002; 66: 319–327.
Ohnuki K, Haramizu S, Oki K, Watanabe T, Yazawa S, Fushiki T . Administration of capsiate, a non-pungent capsaicin analog, promotes energy metabolism and suppresses body fat accumulation in mice. Biosci Biotechnol Biochem 2001; 65: 2735–2740.
Vanhamme L, van den Boogaart A, Van Huffel S . Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 1997; 129: 35–43.
Arnold DL, Matthews PM, Radda GK . Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magn Reson Med 1984; 1: 307–315.
Masuda Y, Haramizu S, Oki K, Ohnuki K, Yazawa S, Kawada T et al. Upregulation of uncoupling proteins by oral administration of capsiate, a nonpungent capsaicin analog. J Appl Physiol 2003; 95: 2408–2415.
Jensen MD . Fate of fatty acids at rest and during exercise: regulatory mechanisms. Acta Physiol Scand 2003; 178: 385–390.
Gong DW, Monemdjou S, Gavrilova O, Leon LR, Marcus-Samuels B, Chou CJ et al. Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. J Biol Chem 2000; 275: 16251–16257.
Cline GW, Vidal-Puig AJ, Dufour S, Cadman KS, Lowell BB, Shulman GI et al. In vivo effects of uncoupling protein-3 gene disruption on mitochondrial energy metabolism. J Biol Chem 2001; 276: 20240–20244.
Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y et al. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 2000; 275: 16258–16266.
Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB et al. Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 2000; 406: 415–418.
Costford SR, Chaudhry SN, Salkhordeh M, Harper ME . Effects of the presence, absence, and overexpression of uncoupling protein-3 on adiposity and fuel metabolism in congenic mice. Am J Physiol Endocrinol Metab 2006; 290: E1304–E1312.
Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S . Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 1987; 36: 54–59.
Ross R, Leger L, Guardo R, De Guise J, Pike BG . Adipose tissue volume measured by magnetic resonance imaging and computerized tomography in rats. J Appl Physiol 1991; 70: 2164–2172.
Mingrone G, Rosa G, Greco AV, Manco M, Vega N, Hesselink MK et al. Decreased uncoupling protein expression and intramyocytic triglyceride depletion in formerly obese subjects. Obes Res 2003; 11: 632–640.
Schrauwen P, Schaart G, Saris WH, Slieker LJ, Glatz JF, Vidal H et al. The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in type II diabetic subjects. Diabetologia 2000; 43: 1408–1416.
Acknowledgements
We are grateful to Ajinomoto Co Inc. (Tokyo, Japan) and Dr Hideo Kawajiri for kind gift of capsiate. This research was financially supported by the French National Research Agency (Grant ANR-07-BLAN-0354), the French Interdisciplinary Small Animal Imaging Program (CEA-CNRS) and the French Muscular Dystrophy Association (AFM).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Faraut, B., Giannesini, B., Matarazzo, V. et al. Capsiate administration results in an uncoupling protein-3 downregulation, an enhanced muscle oxidative capacity and a decreased abdominal fat content in vivo. Int J Obes 33, 1348–1355 (2009). https://doi.org/10.1038/ijo.2009.182
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2009.182