Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis

Abstract

The measurement of fat balance (fat input minus fat output) involves the accurate estimation of both metabolizable fat intake and total fat oxidation. This is possible mostly under laboratory conditions and not yet in free-living conditions. In the latter situation, net fat retention/mobilization can be estimated based on precise and accurate sequential body composition measurements. In case of positive balance, lipids stored in adipose tissue can originate from dietary (exogenous) lipids or from nonlipid precursors, mainly from carbohydrates (CHOs) but also from ethanol, through a process known as de novo lipogenesis (DNL). Basic equations are provided in this review to facilitate the interpretation of the different subcomponents of fat balance (endogenous vs exogenous) under different nutritional circumstances. One difficulty is methodological: total DNL is difficult to measure quantitatively in man; for example, indirect calorimetry only tracks net DNL, not total DNL. Although the numerous factors (mostly exogenous) influencing DNL have been studied, in particular the effect of CHO overfeeding, there is little information on the rate of DNL in habitual conditions of life, that is, large day-to-day fluctuations of CHO intakes, different types of CHO ingested with different glycemic indexes, alcohol combined with excess CHO intakes, etc. Three issues, which are still controversial today, will be addressed: (1) Is the increase of fat mass induced by CHO overfeeding explained by DNL only, or by decreased endogenous fat oxidation, or both? (2) Is DNL different in overweight and obese individuals as compared to their lean counterparts? (3) Does DNL occur both in the liver and in adipose tissue? Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro. The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Jebb SA, Prentice AM, Goldberg GR, Murgatroyd PR, Black AE, Coward WA . Changes in macronutrient balance during over- and underfeeding assessed by 12-d continuous whole-body calorimetry. Am J Clin Nutr 1996; 64: 259–266.

    Article  CAS  PubMed  Google Scholar 

  2. Weyer C, Snitker S, Rising R, Bogardus C, Ravussin E . Determinants of energy expenditure and fuel utilization in man: effects of body composition, age, sex, ethnicity and glucose tolerance in 916 subjects. Int J Obes Relat Metab Disord 1999; 23: 715–722.

    Article  CAS  PubMed  Google Scholar 

  3. Jequier E, Schutz Y . Long-term measurements of energy expenditure in humans using a respiration chamber. Am J Clin Nutr 1983; 38: 989–998.

    Article  CAS  PubMed  Google Scholar 

  4. Saris WH, Schrauwen P . Substrate oxidation differences between high- and low-intensity exercise are compensated over 24 hours in obese men. Int J Obes Relat Metab Disord 2004; 28: 759–765.

    Article  CAS  PubMed  Google Scholar 

  5. Bjorntorp P, Sjostrom L . Carbohydrate storage in man: speculations and some quantitative considerations. Metabolism 1978; 27 (Suppl 2): 1853–1865.

    Article  CAS  PubMed  Google Scholar 

  6. Acheson KJ, Flatt JP . Importance of de novo lipogenesis on energy expenditure in human (letter). Br J Nutr 2001; 86: 309.

    Article  Google Scholar 

  7. Acheson KJ, Schutz Y, Bessard T . Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal. Am J Physiol 1984; 246: E62–E70.

    CAS  PubMed  Google Scholar 

  8. Maffeis C, Armellini F, Tato L, Schutz Y . Fat oxidation and adiposity in prepubertal children: exogenous vs endogenous fat utilization. J Clin Endocrinol Metab 1999; 8: 654–658.

    Article  Google Scholar 

  9. Sonko BJ, Prentice AM, Coward WA, Murgatroyd PR, Goldberg GR . Dose–response relationship between fat ingestion and oxidation: quantitative estimation using whole-body calorimetry and 13C isotope ratio mass spectrometry. Eur J Clin Nutr 2001; 55: 10–18.

    Article  CAS  PubMed  Google Scholar 

  10. Pasquet P, Brigant L, Froment A, Koppert GA, Bard D, de Garine I, Apfelbaum M . Massive overfeeding and energy balance in men: the Guru Walla model. Am J Clin Nutr 1992; 56: 483–490.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hellerstein MK . De novo lipogenesis in humans: metabolic and regulatory aspects. Eur J Clin Nutr 1999; 53 (Suppl 1): S63–S65.

    Google Scholar 

  13. 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.

    Article  CAS  PubMed  PubMed Central  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.

    Article  CAS  PubMed  Google Scholar 

  15. Schutz Y, Acheson KJ, Jequier E . Twenty-four-hour energy expenditure and thermogenesis: response to progressive carbohydrate overfeeding in man. Int J Obes Relat Metab Disord 1985; 9 (Suppl 2): 111–114.

    Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. Schutz Y . Overfeeding experiments: potentials and limitations in obesity research. Br J Nutr 2000; 84 (2): 135–137.

    CAS  PubMed  Google Scholar 

  18. Parks EJ, Hellerstein MK . Effects of low-fat, high carbohydrate diets on serum lipids in humans: a review of the literature. Am J Clin Nutr 2000; 71: 412–433.

    Article  CAS  PubMed  Google Scholar 

  19. Horton TJ, Drougas H, Brachey A, Reed GW, Peters JC, Hill JO . Fat and carbohydrate overfeeding in humans: different effects on energy storage. Am J Clin Nutr 1995; 62: 19–29.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. Sparti A, Milon H, Di Vetta V, Schneiter P, Tappy L, Jéquier E, Schutz Y . Effect of diets high or low in unavailable and slowly digestible carbohydrates on the pattern of 24-h substrate oxidation and feelings of hunger in humans. Am J Clin Nutr 2000; 72: 1461–1468.

    Article  CAS  PubMed  Google Scholar 

  22. Van Wymelbeke V, Beridot-Therond ME, de La Gueronniere V, Fantino M . Influence of repeated consumption of beverages containing sucrose or intense sweeteners on food intake. Eur J Clin Nutr 2004; 58: 154–161.

    Article  CAS  PubMed  Google Scholar 

  23. Schutz Y, Flatt JP, Jéquier E . Failure of dietary fat intake to promote fat oxidation: a factor favoring the development of obesity. Am J Clin Nutr 1989; 50: 307–314.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. Flatt JP . Body composition, respiratory quotient, and weight maintenance. Am J Clin Nutr 1995; 62 (Suppl): 1107S–1117S.

    Article  CAS  PubMed  Google Scholar 

  29. Ravussin E, Schutz Y, Acheson KJ, Dusmet M, Bourquin L, Jequier E . Short-term, mixed-diet overfeeding in man: no evidence for ‘luxuskonsumption’. Am J Physiol 1985; 249: E470–E477.

    CAS  PubMed  Google Scholar 

  30. 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.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. Minehira K, Vega N, Vidal H, Acheson K, Tappy L . 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 Relat Metab Disord 2004; 28: 1291–1298.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. Wang Y, Voy BJ, Urs S, Kim S, Soltani-Bejnood M, Quigley N, Heo Y-R, Standridge M, Andersen B, Dhar M, Joshi R, Wortman P, Taylor JW, Chun J, Leuze M, Claycombe K, Saxton A-M, Moustaid-Moussa N . The human fatty acid synthase gene and de novo lipogenesis are coordinately regulated in human adipose tissue. J Nutr 2004; 134: 1032–1038.

    Article  CAS  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. Aas V, Kase ET, Solberg R, Jensen J, Rustan AC . Chronic hyperglycaemia promotes lipogenesis and triacylglycerol accumulation in human skeletal muscle cells. Diabetologia 2004; 47: 1452–1461.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Y Schutz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schutz, Y. Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis. Int J Obes 28 (Suppl 4), S3–S11 (2004). https://doi.org/10.1038/sj.ijo.0802852

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802852

Keywords

This article is cited by

Search

Quick links