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Body weight and energy homeostasis was not affected in C57BL/6 mice fed high whey protein or leucine-supplemented low-fat diets

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Abstract

Background

Leucine is suggested to act as nutrient signal of high-protein diets regulating pathways associated with an alleviation of metabolic syndrome parameters. However, the subject remains controversial.

Aim of the study

The aim of this study was to assess and to compare the effects of high-protein diets with dietary leucine supplementation in mice, particularly on energy homeostasis, body composition, and expression of uncoupling protein (UCP), which are suggested to decrease food energy efficiency.

Methods

Male C57BL/6 mice were exposed for 14 weeks to semi-synthetic diets containing either 20% (adequate protein content, AP) or 50% whey protein (high-protein content, HP). A third group was fed the AP diet supplemented with L-leucine (AP + L) corresponding to the leucine content of the HP diet. The total fat content was 5% (w/w).

Results

Body weight gain, body composition, energy expenditure, and protein expression of UCP1 in brown adipose tissue, and UCP3 in skeletal muscle were not different between groups. In HP-fed mice, a stronger increase in blood glucose levels was detected during glucose tolerance tests compared to AP and AP + L, whereas plasma insulin was similar in all groups. Leucine supplementation did not affect glucose tolerance. Plasma cholesterol was significantly decreased in HP and AP + L when compared to AP. Plasma triglyceride concentrations were increased twofold in HP-fed mice when compared to AP + L and AP groups. Liver and skeletal muscle triglyceride and glycogen concentrations were similar in all groups. Postabsorptive plasma concentrations of branched-chain amino acids were not significantly increased after exposure to HP and AP + L diets, whereas those of lysine were decreased in HP and AP + L mice when compared to AP (P < 0.001). Plasma methionine concentrations were lower after HP intake when compared to AP and AP + L (P < 0.05).

Conclusions

We suggest that an exposure of mice to HP diets or a corresponding leucine supplementation has no significant effect on energy homeostasis and UCP expression compared with AP diets when feeding a low-fat diet. The use of high-quality whey protein might at least in part explain the results obtained.

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Abbreviations

AP:

Adequate protein diet

AP + L:

AP supplemented with L-leucine

BW:

Body weight

EE:

Energy expenditure

HP:

High-protein diet

LBM:

Lean body mass

NEFA:

Non-esterified fatty acids

RMR:

Resting metabolic rate

RQ:

Respiratory quotient

TEE:

Total energy expenditure

TG:

Triglyceride

UCP:

Uncoupling protein

QMR:

Quantitative magnetic resonance

References

  1. Noatsch A, Petzke KJ, Klaus S (2009) Does leucine of high protein diets play a role in the regulation of energy balance in mice? Amino Acids 37(Suppl 1):107

    Google Scholar 

  2. Westerterp-Platenga MS, Nieuwenhuizen A, Tomé D, Soenen S, Westerterp KR (2009) Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr 29:21–41

    Article  Google Scholar 

  3. Layman DK, Walker DA (2006) Potential importance of leucine in treatment of obesity and the metabolic syndrome. J Nutr 136:319S–3123S

    CAS  Google Scholar 

  4. Kimball SR, Jefferson LS (2006) New functions for amino acids: effects on gene transcription and translation. Am J Clin Nutr 83(Suppl):500S–507S

    CAS  Google Scholar 

  5. Balage M, Dardevet D (2010) Long-term effects of leucine supplementation on body composition. Curr Opin Clin Nutr Metab Care 13:265–270

    Article  CAS  Google Scholar 

  6. Petzke KJ, Friedrich M, Metges CC, Klaus S (2005) Long-term dietary high protein intake up-regulates tissue specific gene expression of uncoupling proteins 1 and 2 in rats. Eur J Nutr 44:414–421

    Article  CAS  Google Scholar 

  7. Petzke KJ, Riese C, Klaus S (2007) Short-term, increasing dietary protein and fat moderately affect enetgy expenditure, substrate oxidation and uncoupling protein gene expression in rats. J Nutr Biochem 18:400–407

    Article  CAS  Google Scholar 

  8. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH (2007) Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56:1647–1654

    Article  CAS  Google Scholar 

  9. Nairizi A, She P, Vary TC, Lynch CJ (2009) Leucine supplementation of drinking water does not alter susceptibility to diet-induced obesity in mice. J Nutr 139:715–719

    Article  CAS  Google Scholar 

  10. She P, Reid TM, Bronson SK, Vary TC, Hajnal A, Lynch CL, Hutson SM (2007) Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metabol 6:181–194

    Article  CAS  Google Scholar 

  11. Chotechuang N, Azzout-Marniche D, Bos C, Chaumontet C, Gausserès N, Steiler T, Gaudichon C, Tomé D (2009) mTOR, AMPK, and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to protein intake in the rat. Am J Physiol Endocrinol Matab 297:E1313–E1323

    Article  CAS  Google Scholar 

  12. Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffe-Scrive M (1995) Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6 and A/J mice. Metabolism 44:645–651

    Article  CAS  Google Scholar 

  13. Petzke KJ, Schuppe S, Rohn S, Rawel HM, Kroll J (2005) Chlorogenic acid moderately decreases the quality of whey proteins in rats. J Agric Food Chem 53:3714–3720

    Article  CAS  Google Scholar 

  14. National Research Council, Subcommittee on Laboratory Animal Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council (1995): Nutrient requirements of the mouse. In: Nutrient requirements of laboratory animals, 4th edn. National Academy Press, Washington (DC), pp 80–102

  15. Klaus S, Rudolph B, Dohrmann C, Wehr R (2005) Expression of uncoupling protein 1 in skeletal muscle decreases muscle energy efficiency and affects thermoregulation and substrate oxidation. Physiol Genomics 21:193–200

    Article  CAS  Google Scholar 

  16. Ortmann S, Kampe J, Gossel M, Bickel M, Geisen K, Jähne G, Lang HJ, Klaus S (2004) A novel anti-obesic HMR1426 reduces food intake without affecting energy expenditure in rats. Obes Res 12:1290–1297

    Article  CAS  Google Scholar 

  17. Katterle Y, Keipert S, Hof J, Klaus S (2008) Dissociation of obesity and insulin resistance in transgenic mice with skeletal muscle expression of uncoupling protein 1. Physiol Genomics 32:352–359

    CAS  Google Scholar 

  18. Klaus S (2005) Increasing the protein:carbohydrate ratio in a high-fat diet delays the development of adiposity and improves glucose homeostasis in mice. J Nutr 135:1854–1858

    CAS  Google Scholar 

  19. Hu CC, Quing K, Chen Y (2004) Diet induced changes in stearoyl-CoA desaturase1 expression in obesity-prone and–resistant mice. Obes Res 12:1264–1270

    Article  CAS  Google Scholar 

  20. Koza RA, Nikonova L, Hogan J, Rim JS, Mendoza T, Faulk C, Skaf J, Kozak LP (2006) Changes in gene expression foreshadow diet-induced obesity in genetically identical mice. PLoS Genet 2:e81

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Lopez N, Sanchez J, Pico C, Palou A, Serra F (2010) Dietary l-leucine supplementation of lactating rats results in a tendency to increase lean/fat ratio associated to lower orexigenic neuropeptide expression in hypothalamus. Peptides 31:1361–1367

    Article  CAS  Google Scholar 

  23. Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrère B (1997) Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA 94:14930–14935

    Article  CAS  Google Scholar 

  24. Daenzer M, Petzke KJ, Bequette BJ, Metges CC (2001) Whole-body nitrogen and splanchnic amino acid metabolism differ in rats fed mixed diets containing casein or its corresponding amino acid mixture. J Nutr 131:1965–1972

    CAS  Google Scholar 

  25. Norton LE, Layman DK, Bunpo P, Anthony TG, Brana DV, Garlick PJ (2009) The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats. J Nutr 139:1103–1109

    Article  CAS  Google Scholar 

  26. Noguchi Y, Shikata N, Furuhata Y, Kimura T, Takahashi M (2008) Characterization of dietary protein-dependent amino acid metabolism by linking free amino acids with transcriptional profiles through analysis of correlation. Physiol Genomics 34:315–326

    Article  CAS  Google Scholar 

  27. Jean C, Rome S, Mathé V, Huneau JF, Aattouri N, Fromentin G, Achagiotis CL, Tomé D (2001) Metabolic evidence for adaptation to a high protein diet in rats. J Nutr 131:91–98

    CAS  Google Scholar 

  28. Blachier F, Lancha AH Jr, Boutry C, Tomé D (2010) Alimentary proteins, amino acids and cholesterolemia. Amino Acids 38:15–22

    Article  CAS  Google Scholar 

  29. Stead LM, Brosnan ME, Brosnan JT (2000) Characterization of homocysteine metabolism in the rat liver. Biochem J 350:685–692

    Article  CAS  Google Scholar 

  30. Kuhla B, Kucia M, Görs S, Albrecht D, Langhammer M, Kuhla S, Metges CC (2010) Effect of a high-protein diet on food intake and liver metabolism during pregnancy, lactation and after weaning in mice. Proteomics 10:2573–2588

    Article  CAS  Google Scholar 

  31. Lacroix M, Gaudichon C, Martin A, Morens C, Mathé V, Tomé D, Huneau J-F (2004) A long-term high-protein diet markedly reduces adipose tissue without major side effects in Wistar male rats. Am J Physiol Regul Integr Comp Physiol 287:R934–R942

    Article  CAS  Google Scholar 

  32. Pichon L, Huneau JF, Fromentin G, Tomé D (2006) A high-protein, high-fat, carbohydrate-free diet reduces energy intake, hepatic lipogenesis, and adiposity in rats. J Nutr 136:1256–1260

    CAS  Google Scholar 

  33. Tomé D, Schwarz J, Darcel N, Fromentin G (2009) Protein, amino acids, vagus nerve signaling, and the brain. Am J Clin Nutr 90(Suppl):838S–843S

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by funding to KJP and SK of the Deutsche Forschungsgemeinschaft, Bonn, Germany (contract/grant number: PE 643/7-1), and by the core budget of the German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. Carola Plaue and Anja Schueler were gratefully acknowledged for excellent technical assistance. All authors read and approved the final manuscript.

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The authors have no conflicts of interest to disclose.

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Correspondence to Klaus J. Petzke.

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Noatsch, A., Petzke, K.J., Millrose, M.K. et al. Body weight and energy homeostasis was not affected in C57BL/6 mice fed high whey protein or leucine-supplemented low-fat diets. Eur J Nutr 50, 479–488 (2011). https://doi.org/10.1007/s00394-010-0155-2

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