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Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet

Abstract

Objective:

Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite.

Subjects:

A total of 44 healthy adult men (aged: 43±5 years; BMI: 27.3±3.2 kg/m2).

Measurements:

Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite.

Results:

After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% CI: −43.6; −34.9%). This decline was associated with an increase in fasting hunger (r=−0.42; P<0.01), desire to eat (r=−0.39; P<0.05) and total appetite (r=−0.38; P<0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period (for total appetite: day 0 r=−0.15, P=0.32; day 2 r=−0.31, P=<0.05; day 4 r=−0.41, P<0.01).

Conclusions:

The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite.

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References

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432.

    Article  CAS  Google Scholar 

  2. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903–908.

    Article  CAS  Google Scholar 

  3. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–546.

    Article  CAS  Google Scholar 

  4. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540–543.

    Article  CAS  Google Scholar 

  5. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341: 879–884.

    Article  CAS  Google Scholar 

  6. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–295.

    Article  CAS  Google Scholar 

  7. Kolaczynski JW, Considine RV, Ohannesian J, Marco C, Opentanova I, Nyce MR et al. Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves. Diabetes 1996; 45: 1511–1515.

    Article  CAS  Google Scholar 

  8. Dubuc GR, Phinney SD, Stern JS, Havel PJ . Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 1998; 47: 429–434.

    Article  CAS  Google Scholar 

  9. Wisse BE, Campfield LA, Marliss EB, Morais JA, Tenenbaum R, Gougeon R . Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women. Am J Clin Nutr 1999; 70: 321–330.

    Article  CAS  Google Scholar 

  10. Leibel RL . The role of leptin in the control of body weight. Nutr Rev 2002; 60: S15–S19; discussion S68–S84, 85–17.

    Article  Google Scholar 

  11. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250–252.

    Article  CAS  Google Scholar 

  12. Flier JS . Obesity wars: molecular progress confronts an expanding epidemic. Cell 2004; 116: 337–350.

    Article  CAS  Google Scholar 

  13. Fried SK, Ricci MR, Russell CD, Laferrere B . Regulation of leptin production in humans. J Nutr 2000; 130: 3127S–3131S.

    Article  CAS  Google Scholar 

  14. Karhunen LJ, Lappalainen RI, Haffner SM, Valve RH, Tuorila H, Miettinen H et al. Serum leptin, food intake and preferences for sugar and fat in obese women. Int J Obes Relat Metab Disord 1998; 22: 819–821.

    Article  CAS  Google Scholar 

  15. Karhunen L, Haffner S, Lappalainen R, Turpeinen A, Miettinen H, Uusitupa M . Serum leptin and short-term regulation of eating in obese women. Clin Sci (London) 1997; 92: 573–578.

    Article  CAS  Google Scholar 

  16. Joannic JL, Oppert JM, Lahlou N, Basdevant A, Auboiron S, Raison J et al. Plasma leptin and hunger ratings in healthy humans. Appetite 1998; 30: 129–138.

    Article  CAS  Google Scholar 

  17. Larsson H, Elmstahl S, Berglund G, Ahren B . Evidence for leptin regulation of food intake in humans. J Clin Endocrinol Metab 1998; 83: 4382–4385.

    CAS  PubMed  Google Scholar 

  18. Stratton RJ, Stubbs RJ, Elia M . Interrelationship between circulating leptin concentrations, hunger, and energy intake in healthy subjects receiving tube feeding. JPEN J Parenter Enteral Nutr 1998; 22: 335–339.

    Article  CAS  Google Scholar 

  19. Romon M, Lebel P, Velly C, Marecaux N, Fruchart JC, Dallongeville J . Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake. Am J Physiol 1999; 277: E855–E861.

    CAS  Google Scholar 

  20. Chapelot D, Aubert R, Marmonier C, Chabert M, Louis-Sylvestre J . An endocrine and metabolic definition of the intermeal interval in humans: evidence for a role of leptin on the prandial pattern through fatty acid disposal. Am J Clin Nutr 2000; 72: 421–431.

    Article  CAS  Google Scholar 

  21. Keim NL, Stern JS, Havel PJ . Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 1998; 68: 794–801.

    Article  CAS  Google Scholar 

  22. Westerterp-Plantenga MS, Saris WH, Hukshorn CJ, Campfield LA . Effects of weekly administration of pegylated recombinant human OB protein on appetite profile and energy metabolism in obese men. Am J Clin Nutr 2001; 74: 426–434.

    Article  CAS  Google Scholar 

  23. Hukshorn CJ, Westerterp-Plantenga MS, Saris WH . Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men. Am J Clin Nutr 2003; 77: 771–776.

    Article  CAS  Google Scholar 

  24. Verschuren WMM, van Leer EM, Blokstra A, Seidell JC, Smit HA, Buena de Mesquita A et al. Cardiovascular disease risk factors in The Netherlands. Neth J Cardiol 1993; 6: 205–210.

    Google Scholar 

  25. Mars M, de Graaf C, van Rossum CT, de Groot CP, Seidell JC, Kok FJ . Leptin and insulin responses to a four-day energy-deficient diet in men with different weight history. Int J Obes Relat Metab Disord 2003; 27: 574–581.

    Article  CAS  Google Scholar 

  26. Van Rossum CTM, Hoebee B, Van Baak M, Mars M, Saris WHM, Seidell JC . Genetic variation in the LEPR gene, leptin and weight gain in Dutch adults. Obes Res 2003; 11: 377–386.

    Article  CAS  Google Scholar 

  27. World Health Organization. Study Group on prevention of Diabetes Mellitus. Prevention of diabetes mellitus, WHO Technical Report series no. 844, Geneva 1994.

  28. Voedingsraad. Nederlandse Voedingsnormen (in Dutch). Nutrition Council. The Hague: Dutch Nutritional guidelines, 1989.

  29. Van Strien T . Eating behaviour personality traits and body mass. Thesis. Human Nutrition, Landbouwhogeschool, Wageningen, 1986.

  30. Hill AJ, Rogers PJ, Blundell JE . Techniques for the experimental measurement of human eating behaviour and food intake: a practical guide. Int J Obes Relat Metab Disord 1995; 19: 361–375.

    CAS  PubMed  Google Scholar 

  31. Hulshof T, De Graaf C, Weststrate JA . Short-term satiating effect of the fat replacer sucrose polyester (SPE) in man. Br J Nutr 1995; 74: 569–585.

    Article  CAS  Google Scholar 

  32. Haluzik M, Matoulek M, Svacina S, Hilgertova J, Haas T . The influence of short-term fasting on serum leptin levels, and selected hormonal and metabolic parameters in morbidly obese and lean females. Endocr Res 2001; 27: 251–260.

    Article  CAS  Google Scholar 

  33. Riad-Gabriel MG, Jinagouda SD, Sharma A, Boyadjian R, Saad MF . Changes in plasma leptin during the menstrual cycle. Eur J Endocrinol 1998; 139: 528–531.

    Article  CAS  Google Scholar 

  34. Buffenstein R, Poppitt SD, McDevitt RM, Prentice AM . Food intake and the menstrual cycle: a retrospective analysis, with implications for appetite research. Physiol Behav 1995; 58: 1067–1077.

    Article  CAS  Google Scholar 

  35. de Graaf C . The validity of appetite ratings. Appetite 1993; 21: 156–160.

    Article  CAS  Google Scholar 

  36. Stubbs RJ, Hughes DA, Johnstone AM, Rowley E, Reid C, Elia M et al. The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr 2000; 84: 405–415.

    Article  CAS  Google Scholar 

  37. Flint A, Raben A, Blundell JE, Astrup A . Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 2000; 24: 38–48.

    Article  CAS  Google Scholar 

  38. World Health Organization. Energy and protein requirements. Report of a Joint FAO/WHO/UNU Expert consultation, WHO Technical report series no. 724, Geneva 1985.

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Acknowledgements

We thank the volunteers who participated in this study; the project steering committee of the Peilstation and MORGEN-project; Caroline de Rover, Irma Thus, Ina Hengeveld of the Municipal Health Service Center in Doetinchem; Els Siebelink, Maartje Jansen and Carolien Bouwman for their assistance during the intervention study. The Netherlands Association for Scientific Research supported this research (ZonMW project no. 980-10-007).

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Mars, M., de Graaf, C., de Groot, C. et al. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet. Int J Obes 30, 122–128 (2006). https://doi.org/10.1038/sj.ijo.0803070

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