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Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans

Abstract

OBJECTIVE: Lipids stored in adipose tissue can originate from dietary lipids or from de novo lipogenesis (DNL) from carbohydrates. Whether DNL is abnormal in adipose tissue of overweight individuals remains unknown. The present study was undertaken to assess the effect of carbohydrate overfeeding on glucose-induced whole body DNL and adipose tissue lipogenic gene expression in lean and overweight humans.

DESIGN: Prospective, cross-over study.

SUBJECTS AND METHODS: A total of 11 lean (five male, six female, mean BMI 21.0±0.5 kg/m2) and eight overweight (four males, four females, mean BMI 30.1±0.6 kg/m2) volunteers were studied on two occasions. On one occasion, they received an isoenergetic diet containing 50% carbohydrate for 4 days prior to testing; on the other, they received a hyperenergetic diet (175% energy requirements) containing 71% carbohydrates. After each period of 4 days of controlled diet, they were studied over 6 h after having received 3.25 g glucose/kg fat free mass. Whole body glucose oxidation and net DNL were monitored by means of indirect calorimetry. An adipose tissue biopsy was obtained at the end of this 6-h period and the levels of SREBP-1c, acetyl CoA carboxylase, and fatty acid synthase mRNA were measured by real-time PCR.

RESULTS: After isocaloric feeding, whole body net DNL amounted to 35±9 mg/kg fat free mass/5 h in lean subiects and to 49±3 mg/kg fat free mass/5 h in overweight subjects over the 5 h following glucose ingestion. These figures increased (P<0.001) to 156±21 mg/kg fat free mass/5 h in lean and 64±11 mg/kg fat free mass/5 h (P<0.05 vs lean) in overweight subjects after carbohydrate overfeeding. Whole body DNL after overfeeding was lower (P<0.001) and glycogen synthesis was higher (P<0.001) in overweight than in normal subjects. Adipose tissue SREBP-1c mRNA increased by 25% in overweight and by 43% in lean subjects (P<0.05) after carbohydrate overfeeding, whereas fatty acid synthase mRNA increased by 66 and 84% (P<0.05).

CONCLUSION: Whole body net DNL is not increased during carbohydrate overfeeding in overweight individuals. Stimulation of adipose lipogenic enzymes is also not higher in overweight subjects. Carbohydrate overfeeding does not stimulate whole body net DNL nor expression of lipogenic enzymes in adipose tissue to a larger extent in overweight than lean subjects.

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References

  1. Hellerstein MK, Christiansen M, Kaempfer S . Measurement of de novo hepatic lipogenesis in humans using stable isotopes. J Clin Invest 1991; 87: 1841–1852.

    CAS  Article  Google Scholar 

  2. Schwarz J-M, Neese RA, Turner S, Dare D, Hellerstein MK . Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection. J Clin Invest 1995; 96: 2735–2743.

    CAS  PubMed  Google Scholar 

  3. Siler SQ, Neese RA, Hellerstein MK . De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am J Clin Nutr 1999; 70: 928–936.

    CAS  Article  Google Scholar 

  4. McDevitt RM, Bott SJ, Harding M, Coward WA, Bluck LJ, Prentice AM . De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women. Am J Clin Nutr 2001; 74: 737–746.

    CAS  Article  Google Scholar 

  5. Marques-Lopes I, Ansorena D, Astiasaran I, Forga L, Martinez JA . Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men. Am J Clin Nutr 2001; 73: 253–261.

    CAS  Article  Google Scholar 

  6. Shimomura L, Matsuda M, Hammer RE, Bashmakov Y, Brown MS, Goldstein JL . Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell 2000; 6: 77–86.

    CAS  Article  Google Scholar 

  7. Schwarz JM, Linfoot P, Dare D, Aghajanian K . Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 2003; 77: 43–50.

    CAS  Article  Google Scholar 

  8. Tappy L, Schwarz JM, Schneiter P, Cayeux C, Revelly JP, Fagerquist CK, Jéquier E, Chioléno R . Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients. Crit Care Med 1998; 26: 860–867.

    CAS  Article  Google Scholar 

  9. Angel A, Bray GA . Synthesis of fatty acids and cholesterol by liver, adipose tissue and intestinal mucosa from obese and control patients. Eur J Clin Invest 1979; 9: 355–362.

    CAS  Article  Google Scholar 

  10. Guo ZK, Cella LK, Baum C, Ravussin E, Schoeller DA . De novo lipogenesis in adipose tissue of lean and obese women: application of deuterated water and isotope ratio mass spectrometry. Int J Obes Relat Metab Disord 2000; 24: 932–937.

    CAS  Article  Google Scholar 

  11. Strawford A, Antelo F, Christiansen M, Hellerstein MK . Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am J Physiol Endocrinol Metab 2004; 286: E577–E588.

    CAS  Article  Google Scholar 

  12. Acheson K, Flatt J, Jéquier E . Glycogen synthesis versus lipogenesis after a 500 gram carbohydrate meal in man. Metabolism 1982; 31: 1234–1240.

    CAS  Article  Google Scholar 

  13. Acheson K, Schutz Y, Bessard T, Anantharaman K, Flatt J, Jéquier E . Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr 1988; 48: 240–247.

    CAS  Article  Google Scholar 

  14. Aarsland A, Chinkes D, Wolfe RR . Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding. Am J Clin Nutr 1997; 65: 1774–1782.

    CAS  Article  Google Scholar 

  15. Minehira K, Betts V, Vidal H, Vega N, Di Vetta V, Rey V, Scheiter PH, Tappy L . Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans. Obes Res 2003; 11: 1096–1103.

    Article  Google Scholar 

  16. Diraison F, Dusserre E, Vidal H, Sothier M, Beylot M . Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity. Am J Physiol Endocrinol Metab 2002; 282: E46–E51.

    CAS  Article  Google Scholar 

  17. Durnin JVGA, Womersley J . Body fat assessment for total body density and its estimation from skinfold thickness: measurement 481 men and women from 16 to 72 years. Br J Nutr 1979; 32: 77–97.

    Article  Google Scholar 

  18. Livesey G, Elia M . Estimation of energy expenditure, net carbohydrate utilization, and net fat oxidation and synthesis by indirect calorimetry; evaluation of errors with special reference to the detailed composition of foods. Am J Clin Nutr 1988; 47: 608–628.

    CAS  Article  Google Scholar 

  19. Vidal H . Quantification of lipid-related mRNAs by reverse transcription-competitive polymerase chain reaction in human white adipose tissue biopsies. Methods Mol Biol 2001; 155: 83–88.

    CAS  PubMed  Google Scholar 

  20. Jéquier E, Acheson K, Schutz Y . Assessment of energy expenditure and fuel utilization in man. Annu Rev Nutr 1987; 7: 187–208.

    Article  Google Scholar 

  21. Wolfe RR . Tracers in Metabolic Research Radioisotope and Stable Isotope/mass Spectrometry Methods. Liss Alan R. Inc.: New York; 1984.

    Google Scholar 

  22. Acheson KJ, Schutz Y, Bessard T, Flatt JP, Jéquier E . Carbohydrate metabolism and de novo lipogenesis in human obesity. Am J Clin Nutr 1987; 45: 78–85.

    CAS  Article  Google Scholar 

  23. McDevitt RM, Poppitt SD, Murgatroyd PR, Prentice AM . Macronutrient disposal during controlled overfeeding with glucose, fructose, sucrose, or fat in lean and obese women. Am J Clin Nutr 2000; 72: 369–377.

    CAS  Article  Google Scholar 

  24. Hellerstein M, Schwarz J, Nees R . Regulation of hepatic de novo lipogenesis in humans. Annu Rev Nutr 1996; 16: 523–557.

    CAS  Article  Google Scholar 

  25. Kolehmainen M, Vidal H, Alhava E, Uusitupa MIJ . Sterol regulatory element binding protein 1c (SREBP-1c) expression in human obesity. Obes Res 2001; 9: 706–712.

    CAS  Article  Google Scholar 

  26. Ferrannini E . The theoretical bases of indirect calorimetry. A review. Metabolism 1988; 37: 287–301.

    CAS  Article  Google Scholar 

  27. Shulman G, Rothman D, Jue T, Stein P, DeFronzo R, Shulman R . Quantitation of muscle glycogen synthesis in normal subjects and in subjects with non-insulin dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 1990; 322: 223–228.

    CAS  Article  Google Scholar 

  28. Parks EJ, Krauss RM, Christiansen MP, Neese RA, Hellerstein MK . Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance. J Clin Invest 1999; 104: 1087–1096.

    CAS  Article  Google Scholar 

  29. Parks EJ, Hellerstein MK . Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 2000; 71: 412–433.

    CAS  Article  Google Scholar 

  30. Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J . Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest 1996; 97: 2081–2091.

    CAS  Article  Google Scholar 

  31. Hudgins LC, Seidman CE, Diakun J, Hirsch J . Human fatty acid synthesis is reduced after the substitution of dietary starch for sugar. Am J Clin Nutr 1998; 67: 631–639.

    CAS  Article  Google Scholar 

  32. Hellerstein MK . No common energy currency: de novo lipogenesis as the road less traveled. Am J Clin Nutr 2001; 74: 707–708.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant (# 3200-067787.02) from the Swiss Science Foundation and the Désireé and Niels de Foundation.

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Correspondence to L Tappy.

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Minehira, K., Vega, N., Vidal, H. et al. Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans. Int J Obes 28, 1291–1298 (2004). https://doi.org/10.1038/sj.ijo.0802760

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Keywords

  • glucose oxidation
  • nonoxidative glucose disposal
  • insulin
  • SREBP-1c
  • fatty acid synthase

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