Home arrow Research and Review arrow Crank up the heat: Uncoupling Proteins
Subscribe to MD Magazine

MD's Research and Review
muscular development
muscular development
muscular development

PDF Print E-mail
Written by Robbie Durand   
Tuesday, 20 January 2009
Article Index
Crank up the heat: Uncoupling Proteins
Page 2
Page 3

Caffeine and Growth Hormone Increases UCP-3 Activity

Resting metabolic rate can be increased by 30% by the sympathetic nervous system agents27 and by about 15% by growth hormone28.  Growth hormone has also been shown to increase UCP-3 in muscle which may be a part of GH's powerful effect on fat loss39, 40.    Any supplement that increases adrenaline should increase UCP-3 activity.  UCP-3 activity varies between people; research has demonstrated that of all of these possible regulators of the expression of the UCP3 between people, only norepinephrine (a sympathetic catecholamine) could explain part of the variability between UCP-3 expression in subjects. Interestingly, norepinephrine urinary excretion also correlated with resting energy expenditure34.  It should be of no surprise that many of the fat loss supplements target fat loss by increasing norepinephrine levels.  Basically, the higher your norepinephrine levels are, the higher your resting energy expenditure and UCP-3 activity will be.  Caffeine is a potent stimulator of norepinephrine and increases fatty acid mobilization has also been shown to increase UCP-3 activity38.  I suspect the combination of caffeine with ephedrine and yohimbine would further increase UCP-3 activity as all increase norepinephrine levels but no research is available. 

 

Olive Oil, Palm Oil, and Fish Oils: Potent Stimulators of UCP-3

 

UCP-3 is upregulated in situations where fatty acid availability is higher than its oxidation rates, as for example fasting, treatment with thyroid, high-fat/high protein diets, and intense exercise8.  UCP's are activated much more effectively by palm oil, olive oil, and fish oils than by saturated fats. Instead of consuming saturated fats before a competition, you may be get leaner by consuming more fish oils and olive oils.  Researchers conducted a study to determine what fats led to the greatest increase in UCP.  The results were as follow: 1. Palmitic acid (palm oil) 2. Oleic acid (olive oil) 3. Eicosatrienoic acid (omega 3 fatty acid) 4. Linoleic acid (safflower and sunflower oils) 5. Arachidonic acids (meat, eggs, dairy fats).  Palm oil might be another consideration as palm oil can increase UCP-3 activity as well.  It has been shown that palmitic acid or palm oil led to a 10% increase in oxygen consumption.  Consistent with previous studies showing that palm oil not only increases resting oxygen consumption but the expression of the UCP3 gene is approximately doubled by palmitic acid concentrations24.  Another potent stimulator of UCP-3 is olive oil.  After the various types of fat, there was an up-regulating effect of olive oil on UCP-3 expression in muscle. The expression of the UCP3 mRNA in muscle was significantly higher after olive oil feeding than beef fats. Total-body oxygen consumption, an index of resting metabolic rate, was significantly higher in rats fed olive oil than other fats tested 33.  The results of the data suggest that palm oil, olive oil, and fish oils are better stimulators of UCP-3 production than saturated fats17. Thus, not all fats are equal and certain types of fats can enhance diet-induced UCP-3 production in muscle.

 

Blocking Fats Reduce UCP-3 Expression

Clinical data also demonstrate a strong correlation between the amount of circulating fatty acid concentrations and skeletal muscle UCP-3, suggesting fat intake stimulates UCP-3 expression25.   Mingrone and colleagues found a 35% reduction in UCP-3 protein levels in subjects having undergone gastric bypass surgery 22. But since gastric bypass surgery minimizes stomach capacity and reduces dietary fat absorption, the drop in fat absorption likely lowered UCP-3 expression in muscle.  Additionally, Dr. Civaterese at Pennington Biomedical Research center has shown that glucose ingestion during exercise lowered UCP-3 expression and other genes involved in fatty acid metabolism26.  The reduced expression of lipid metabolism genes during glucose ingestion during exercise may have been due in part to suppressed lipolysis and a lowering of circulating fatty acids.  The new over the counter "fat blocker" drug "Alli" will probably lead to a reduced expression of UCP-3 I suspect, but no research is available at this time.

 

Leucine: The Ultimate Diet Amino Acid?

Leucine is an essential, branched chain amino acid that not only as a building block for protein synthesis, but is also a potent activator of the mammalian target of rapamycin (mTOR), a potent activator of may functions including protein synthesis, cell growth, and metabolism. Branched chain Amino Acids, especially leucine, have been speculated to play a key role in regulating metabolism. For example, Donato et al reported that leucine supplementation during caloric restriction results in more fat loss and improves protein synthesis in muscle31.  Get ready for more exciting news on leucine and fat loss.  It was recently shown that doubling leucine intake while on a high calories diet substantially reduced diet-induced weight gain and improved glucose and cholesterol metabolism in mice. The use of L-leucine supplementation also resulted from increased resting energy expenditure associated with increased UCP-3 protein expression in skeletal muscle and in brown and white adipose tissues32.  So leucine not only increases protein synthesis but also reduces bodyfat by increasing UCP-3....can't get much better than that!! Leucine is the one supplement you can't do without before a competition.

 

Key Points:

  • UCP-3 is increased by growth hormone, thyroid, catecholamines, and caffeine.
  • UCP-3 is stimulated more by olive oil, palm oil, and fish oil than saturated fats.
  • UCP-3 is reduced by high carbohydrates and Fat Blockers.
  • New research suggests that Leucine stimulates UCP-3 expression in muscle.

 

 

 

1.      Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC.

Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

2.      Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004 May 18;140(10):769-77.

3.      Cameron-Smith D, Burke LM, Angus DJ, Tunstall RJ, Cox GR, Bonen A, Hawley JA, Hargreaves M. A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle. Am J Clin Nutr. 2003 Feb;77(2):313-8.

4.      Pilegaard H, Osada T, Andersen LT, Helge JW, Saltin B, Neufer PD. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. Metabolism. 2005 Aug;54(8):1048-55.

5.      Young ME, Goodwin GW, Ying J, et al. Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids. Am J Physiol Endocrinol Metab 2001;280:E471-9.

6.      Samec S, Seydoux J, Dulloo AG. Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition: a link with insulin resistance. Diabetes 1999;48:436-41

7.      Cameron-Smith D, Burke LM, Angus DJ, Tunstall RJ, Cox GR, Bonen A, Hawley JA, Hargreaves M. A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle. Am J Clin Nutr. 2003 Feb;77(2):313-8.

8.      Hirabara SM, Silveira LR, Abdulkader FR, Alberici LC, Procopio J, Carvalho CR, Pithon-Curi TC, Curi R. Role of fatty acids in the transition from anaerobic to aerobic metabolism in skeletal muscle during exercise. Cell Biochem Funct. 2006 Nov-Dec;24(6):475-81. Review.

9.      Westerterp-Plantenga MS. The significance of protein in food intake and body weight regulation. Curr Opin Clin Nutr Metab Care 2003;6:635- 8.

10. Halton TL, Hu FB. The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr.  2004;23:373- 85.

11. Mikkelsen PB, Toubro S, Astrup A. Effect of fat-reduced diets on 24-h energy expenditure: comparisons between animal protein, vegetable protein, and carbohydrate. Am J Clin Nutr 2000;72:1135- 41.

12. Nedergaard J, Bengtsson T, Cannon B. Unexpected Evidence for Active Brown Adipose Tissue in Adult Humans. Am J Physiol Endocrinol Metab. 2007 May 1

13. Argyropoulos G, Harper ME. Uncoupling proteins and thermoregulation. J Appl Physiol. 2002 May;92(5):2187-98.

14. Krauss S, Zhang CY, Lowell BB. The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol. 2005 Mar;6(3):248-61. Review.

15. Garruti G, Ricquier D. Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans. Int J Obes Relat Metab Disord. 1992 May;16(5):383-90.

16. Cortright RN, Zheng D, Jones JP, Fluckey JD, DiCarlo SE, Grujic D, Lowell BB, Dohm GL. Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation. Am J Physiol. 1999 Jan;276(1 Pt 1):E217-21.

17. Hirabara SM, Silveira LR, Alberici LC, Leandro CV, Lambertucci RH, Polimeno GC, Cury Boaventura MF, Procopio J, Vercesi AE, Curi R. Acute effect of fatty acids on metabolism and mitochondrial coupling in skeletal muscle. Biochim Biophys Acta. 2006 Jan;1757(1):57-66.

18. Gong DW, He Y, Karas M, Reitman M. Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. J Biol Chem. 1997 Sep 26;272(39):24129-32.

19. Harper JA, Stuart JA, Jekabsons MB, Roussel D, Brindle KM, Dickinson K, Jones RB, Brand MD. Artifactual uncoupling by uncoupling protein 3 in yeast mitochondria at the concentrations found in mouse and rat skeletal-muscle mitochondria. Biochem J. 2002 Jan 1;361(Pt 1):49-56.

20. Mills EM, Weaver KL, Abramson E, Pfeiffer M, Sprague JE. Influence of dietary fats on ecstasy-induced hyperthermia. Br J Pharmacol. 2007.

21. 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 Jun;290(6):E1304-12.

22. Vettor R, Mingrone G, Manco M, Granzotto M, Milan G, Scarda A, Lombardi A, Greco AV, Federspil G. Reduced expression of uncoupling proteins-2 and -3 in adipose tissue in post-obese patients submitted to biliopancreatic diversion. Eur J Endocrinol. 2003 May;148(5):543-50.

23. Schrauwen P, Schaart G, Saris WH, Slieker LJ, Glatz JF, Vidal H, Blaak EE. The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects. Diabetologia. 2000 Nov;43(11):1408-16.

24. Son C, Hosoda K, Matsuda J, Fujikura J, Yonemitsu S, Iwakura H, Masuzaki H, Ogawa Y, Hayashi T, Itoh H, Nishimura H, Inoue G, Yoshimasa Y, Yamori Y, Nakao K. Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for PPARs in L6 myotubes. Endocrinology. 2001 Oct;142(10):4189-94.

25. Sbraccia P, D'Adamo M, Leonetti F, Buongiorno A, Silecchia G, Basso MS, Tamburrano G, Lauro D, Federici M, Di Daniele N, Lauro R. Relationship between plasma free fatty acids and uncoupling protein-3 gene expression in skeletal muscle of obese subjects: in vitro evidence of a causal link. Clin Endocrinol (Oxf). 2002 Aug;57(2):199-207.

26. Civitarese AE, Hesselink MK, Russell AP, Ravussin E, Schrauwen P. Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes. Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E1023-9.

27. Schiffelers SLH, Blaak EE, Saris WHM, van Baak MA. In vivo b3-adrenergic stimulation of human thermogenesis and lipid use. Clin Pharmacol Ther 2000; 67: 558-566.

28. Bray GA. Calorigenic effect of human growth hormone in obesity. J Clin Endocrinol Metab. 29: 119-122. 3

29. Clapham JC, Arch JR. Thermogenic and metabolic antiobesity drugs: rationale and opportunities. Diabetes Obes Metab. 2007 May;9(3):259-75. Review.

30. Nagase I, Yoshida T, Saito M. Up-regulation of uncoupling proteins by beta-adrenergic stimulation in L6 myotubes. FEBS Lett. 2001 Apr 13;494(3):175-80.

31. Donato J, Jr., Pedrosa RG, Cruzat VF, Pires IS, Tirapegui J: Effects of leucine supplementation on the body composition and protein status of rats submitted to food restriction. Nutrition 22:520-527., 2006

32. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes. 2007 Jun;56(6):1647-54.

33. Rodriguez VM, Portillo MP, Pico C, Macarulla MT, Palou A. Olive oil feeding up-regulates uncoupling protein genes in rat brown adipose tissue and skeletal muscle. Am J Clin Nutr. 2002 Feb;75(2):213-20.

34. Boivin M, Camirand A, Carli F, Hoffer LJ, Silva JE. Uncoupling protein-2 and -3 messenger ribonucleic acids in adipose tissue and skeletal muscle of healthy males: variability, factors affecting expression, and relation to measures of metabolic rate. J Clin Endocrinol Metab. 2000 May;85(5):1975-83.

35. Colman E. Dinitrophenol and obesity: An early twentieth-century regulatory dilemma. Regul Toxicol Pharmacol. 2007 Jul;48(2):115-7. Epub 2007 Mar 31.

36. Bezaire V, Hofmann W, Kramer JK, Kozak LP, Harper ME: Effects of fasting on muscle mitochondrial energetics and fatty acid metabolism in Ucp3-/- and wild-type mice. Am J Physiol Endocrinol Metab281 :E975 -E982,2001

37. Hesselink MK, Mensink M, Schrauwen P. Human uncoupling protein-3 and obesity: an update. Obes Res. 2003 Dec;11(12):1429-43. Review.

38. Kogure A, Sakane N, Takakura Y, Umekawa T, Yoshioka K, Nishino H, Yamamoto T, Kawada T, Yoshikawa T, Yoshida T. Effects of caffeine on the uncoupling protein family in obese yellow KK mice. Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):391-4.

39. Pedersen SB, Kristensen K, Fisker S, Jorgensen JO, Christiansen JS, Richelsen B. Regulation of uncoupling protein-2 and -3 by growth hormone in skeletal muscle and adipose tissue in growth hormone-deficient adults. J Clin Endocrinol Metab. 1999 Nov;84(11):4073-8.

40. Hioki C, Yoshida T, Kogure A, Takakura Y, Umekawa T, Yoshioka K, Shimatsu A, Yoshikawa T. Effects of growth hormone (GH) on mRNA levels of uncoupling proteins 1, 2, and 3 in brown and white adipose tissues and skeletal muscle in obese mice. Horm Metab Res. 2004 Sep;36(9):607-13.

 

 

 


 
< Prev   Next >

 Gallery Links