Early potential effects of resveratrol supplementation on skeletal muscle adaptation involved in exercise-induced weight loss in obese mice

  • Sun, Jingyu (Sports and Health Research Center, Tongji University Department of Physical Education) ;
  • Zhang, Chen (Tongji University School of Medicine) ;
  • Kim, MinJeong (Chung-Ang University College of Medicine) ;
  • Su, Yajuan (Tongji University School of Life Sciences and Technology) ;
  • Qin, Lili (Sports and Health Research Center, Tongji University Department of Physical Education) ;
  • Dong, Jingmei (Sports and Health Research Center, Tongji University Department of Physical Education) ;
  • Zhou, Yunhe (Sports and Health Research Center, Tongji University Department of Physical Education) ;
  • Ding, Shuzhe (Key Laboratory of Adolescent Health Assessment and Exercise Intervention, East China Normal University)
  • Received : 2017.12.27
  • Accepted : 2018.03.02
  • Published : 2018.04.30


Exercise and resveratrol supplementation exhibit anti-obesity functions in the long term but have not been fully investigated yet in terms of their early potential effectiveness. Mice fed with high-fat diet were categorized into control (Cont), exercise (Ex), resveratrol supplementation (Res), and exercise combined with resveratrol supplementation (Ex + Res) groups. In the four-week period of weight loss, exercise combined with resveratrol supplementation exerted no additional effects on body weight loss but significantly improved whole-body glucose and lipid homeostasis. The combined treatment significantly decreased intrahepatic lipid content but did not affect intramyocellular lipid content. Moreover, the treatment significantly increased the contents of mtDNA and cytochrome c, the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and its downstream transcription factors, and the activities of ATPase and citrate synthase. However, exercise, resveratrol, and their combination did not promote myofiber specification toward slow-twitch type. The effects of exercise combined with resveratrol supplementation on weight loss could be partly due to enhanced mitochondrial biogenesis and not to fiber-type shift in skeletal muscle tissues.


Endurance exercise;Glucose and lipids homeostasis;Resveratrol;Skeletal muscle adaptation;Weight loss


Supported by : National Natural Science Foundation of China, National Sports General Administration of China, Shanghai Municipal Sports Bureau


  1. Chin SH, Kahathuduwa CN and Binks M (2016) Physical activity and obesity: what we know and what we need to know. Obes Rev 17, 1226-1244
  2. Normandin E, Chmelo E, Lyles MF, Marsh AP and Nicklas BJ (2017) Effect of Resistance Training and Caloric Restriction on the Metabolic Syndrome. Med Sci Sports Exerc 49, 413-419
  3. Timmers S, Konings E, Bilet L et al (2011) Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 14, 612-622
  4. Haohao Z, Guijun Q, Juan Z, Wen K and Lulu C (2015) Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion. J Physiol Biochem 71, 121-131
  5. Sparks LM, Xie H, Koza RA et al (2005) A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes 54, 1926-1933
  6. Civitarese AE, Ukropcova B, Carling S et al (2006) Role of adiponectin in human skeletal muscle biogenesis. Cell Metab 4, 75-87
  7. Mootha VK, Lindfren CM, Eriksson KF et al (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34, 267-273
  8. Heilbronn LK, Gan SK, Turner N, Campbell LV and Chisholm DJ (2007) Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects. J Clin Endocrinol Metab 92, 1467-1473
  9. Bonnard C, Durand A, Peyrol S et al (2008) Mitochondrial dysfunction results from oxidative stress in skeletal muscle of diet-induced insulin resistant mice. J Clin Invest 118, 789-800
  10. Benton CR, Wright DC and Bonen A (2008) PGC-1alphamediated regulation of gene expression and metabolism: implications for nutrition and exercise prescriptions. Appl Physiol Nutr Metab 33, 843-862
  11. Despres JP, Lemieux I, Bergeron J et al (2008) Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 28, 1039-1049
  12. Brouwers B, Hesselink MK, Schrauwen P and Schrauwen-Hinderling VB (2016) Effects of exercise training on intrahepatic lipid content in humans. Diabetologia 59, 2068-2079
  13. Ahn J, Cho I, Kim S, Kwon D and Ha T (2008) Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J Hepatol 9, 1019-1028
  14. Savage DB, Petersen KF and Shulman GI (2007) Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 87, 507-520
  15. Helge JW and Dela F (2003) Effect of training on muscle triacylglycerol and structural lipids: a relation to insulin sensitivity? Diabetes 52, 1881-1887
  16. Goodpaster BH, He J, Watkins S and Kelley DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86, 5755-5761
  17. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R and Dela F (2007) Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50, 790-796
  18. Holloway GP, Thrush AB, Heigenhauser GJ et al (2007) Skeletal muscle mitochondrial FAT/CD36 content and palmitate oxidation are not decreased in obese women. Am J Physiol Endocrinol Metab 292, E1782-1789
  19. Wu Z, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115-124
  20. Ji LL and Kang C (2015) Role of PGC-$1{\alpha}$ in sarcopenia: etiology and potential intervention-a mini-review. Gerontology 61, 139-148
  21. Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ and Wackerhage H (2005) Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 19, 786-788
  22. Valero T (2014) Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des 20, 5507-5509
  23. Lin J, Wu H, Tarr PT et al (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418, 797-801
  24. Sun J, Huang T, Qi Z et al (2017) Early Mitochondrial Adaptations in Skeletal Muscle to Obesity and Obesity Resistance Differentially Regulated by High-Fat Diet. Exp Clin Endocrinol Diabetes 125, 538-546
  25. O'Neill BT, Kim J, Wende AR et al (2007) A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab 6, 294-306