Understanding Leptin For Fat Loss

Lepti-what??

leptin It’s name is Leptin (derived from the Greek word leptos, meaning “thin”), and it’s without a doubt the most important hormone you probably never heard of.

You see, leptin was only first discovered just over 10 years ago, and as far as weight loss is concerned, that’s extremely recent.

Leptin’s function? To communicate your nutritional status to your body and brain.

Leptin levels are mediated by two things. One is your level of body fat. All else being equal, people with higher levels of body fat will have higher leptin levels than those with lower levels of body fat and vice versa.

Because leptin is secreted by fat cells, it makes sense that under normal conditions there is a direct correlation between leptin levels and the amount of fat you are carrying.

Unfortunately, when you’re attempting to lose fat and begin to restrict calories, conditions are anything but “normal” and the body responds accordingly by lowering leptin levels.

This is because the second mediator of blood leptin levels is your calorie intake. Lower your calorie intake and leptin will fall, independent of body fat.

So, yes, you can be overweight and still suffer from low leptin levels – just go on a diet.

So what happens when leptin levels fall and why the heck does it matter?

Again, under normal conditions leptin levels are normal and the brain gets the signal loud and clear that nutrition intake is adequate. Metabolism is high and the internal environment of the body is one very conducive to fat burning.

Until you start dieting.

Go on a diet and leptin levels quickly plummet (by 50% or more after only one week), sending a signal to the body that you’re semi-starved and not consuming enough calories.

This puts the breaks on metabolism and creates a hormonal environment extremely conducive to fat storage. Thyroid hormones (hormones extremely important to metabolism) respond by taking a dive and the abdominal fat-storing stress hormone cortisol skyrockets measurably.

Hello belly fat.

And if that wasn’t bad enough, the appetite stimulating hormones ghrelin, neuropeptide-Y, and anandamide all hop on board to make your life even more miserable.

You don’t have to remember any of those names, just remember that when leptin drops, you get seriously hungry.

Despite having a pretty good reason for its reaction, it’s pretty ironic that our bodies are primed for fat loss at every other time except when we are trying to burn fat.

Wouldn’t it be great if we could maintain high leptin levels and a body primed for fat burning while dieting? It would seemingly solve all of our problems.

But in order to do this, we’d have to somehow keep leptin levels high as we attempt to lose those extra pounds.

How about “supplementing” with leptin?

A couple of problems here: First, leptin is a protein based hormone, which means that it can not be taken orally (otherwise, it would simply be digested). So that rules out a leptin pill.

This leaves the method of “supplemental” leptin administration to injection. And leptin injections DO indeed work, reversing the metabolic adaptations to dieting and “starvation” even while continuing to restrict calories.

In 1996, Ahima et al. used leptin injections to reverse starvation-induced neuroendrocrine adaptations in mice.

“Well, that’s nice and all, but I’m human.” Point taken; research with rodents doesn’t always correlate to similar findings in humans, however…

In 1999, Heymsfield et al. performed a double-blind placebo controlled study analyzing weight loss over a 24-week period in 73 obese humans. Subjects either injected daily with leptin or a placebo (i.e. bogus alternative). At the end of the 24-week period, the leptin group lost significantly more weight than the placebo and a higher percentage of fat vs. muscle.

In 2002, Rosenbaum et al. administered low-dose leptin to subjects (male and female) who had dieted to a 10% decrease in body weight. During the diet period, thyroid hormone levels, 24-hr energy expenditure, and other metabolic markers substantially decreased. The result of the leptin replacement therapy?

“All of these endocrine changes were reversed…”

Thyroid output and daily calorie burn increased back to pre-diet levels.

In 2003, Fogteloo et al. showed that leptin injections “tended to reduce the decline of energy expenditure associated with energy restriction, whereas the tendency of energy intake to increase back to baseline levels in placebo-treated subjects was largely prevented in subjects treated with leptin.”
Yeah, that’s a mouthful. Let me put in simple terms: not only did the leptin group experience less of a decline in metabolism, but they were also less hungry, allowing them to more easily stick to the prescribed diet.

In 2004, Welt et al. reported that leptin given to a group of women with thyroid disorder immediately raised circulating concentrations of the thyroid hormones T3 and T4.

In 2005, Rosenbaum and company were at it again, again showing that energy expenditure and circulating concentrations of T3 and T4 all returned to pre-weight-loss levels with regular leptin injections.

So, as theorized, keeping leptin levels high during a diet does indeed solve our dilemma by avoiding the negative metabolic (and perhaps behavioral) adaptations that calorie restriction perpetuates.

The problem?

Daily leptin injections are far too expensive, costing thousands and thousands of dollars per week. So, we can pretty much forget about supplemental leptin as a solution (which is probably moot anyway considering that not too many people are going to voluntarily plunge a needle into their skin daily).

A REAL Solution

Now that we know that leptin injections aren’t going to save us, let’s talk about the possibility of manipulating your body’s natural leptin production.

And I’ve got good news – this can indeed be done, and without involving needles or thousands of dollars. In fact, we’ll swap the injections and mounds of cash out for two things I can guarantee you’re absolutely going to love: more calories and more carbs.

We know that leptin levels decrease by about 50% after only one week of dieting, but fortunately, it doesn’t take nearly that long for leptin to bump back up with a substantial increase in caloric intake.

In fact, research has shown that it only takes about 12-24 hours.

So, the answer to the fat loss catch-22? Strategic high-calorie, high-carb CHEATING.

pizza By strategically cheating with high calorie foods (and yes, even stuff like pizza, ice cream, wings, cookies, burgers, fries, etc), you can give leptin and metabolism a major boost mid-diet which sets you up for plenty of subsequent fat loss when you resume your reduced calorie eating regimen.

This means greater net fat loss week after week, and ultimately, a much more realistic, maintainable way to bring you to the body you truly want and deserve.

So what’s so special about carbs?

Well, leptin, carbohydrate and insulin have been shown to have very strong ties.

Calories alone don’t get the job done, as research shows that overfeeding on protein and fat has little effect on leptin.

In order to get a strong leptin response from overfeeding, there needs to be plenty of carbs in the mix. In fact, the relationship is SO strong that research conducted by Boden et al. at the Temple University School of Medicine shows that leptin levels will not fall even in response to all-out fasting so long as insulin and blood sugar are maintained via IV drip (16). That’s CRAZY.

Because of this carbohydrate/insulin-leptin relationship, it makes sense that foods combining both carbs and fat (like pizza, burgers, cookies, ice cream, etc) work best for reversing the negative adaptations caused by dieting because of the BIG-TIME insulin response they produce.

But even more importantly, this relationship gives us an indicator of just how important and useful carbohydrates are on “diet” days.

And THAT'S what I’ll be back to talk with you about tomorrow. How we use strategic carbohydrate cycling along with planned cheating in the Cheat Your Way Thin program to ensure that you never go a single day without a body primed for fat loss.

Stay tuned; our journey continues tomorrow...

In the meantime, if you did not read my MOST embarrassing admission from Friday, be sure to go do that now by clicking HERE. It's the ONLY reason Cheat Your Way Thin exists.

Here's to loving your diet (and I promise you will),

signature

Joel

Joel Marion, CISSN, NSCA-CPT
2001 Body-for-Life Grand Champion
Men's Fitness Training Advisory Team
LifeScript.com Women's Fitness Expert Panel

P.S. Oh, just in case you were wondering, I didn't just make all that stuff up; 85 research papers later...

References

1. Dubuc GR, Havel PJ et al. Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism. 1998 Apr;47(4):429-34.

2. Klein S, et al. Leptin production during early starvation in lean and obese women. Am J Physiol Endocrinol Metab. 2000 Feb;278(2):E280-4.

3. Dirlewanger M, et al. Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects. Int J Obes Relat Metab Disord. 2000 Nov;24(11):1413-8.

4. Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413-37. Review.

5. Bowles L, Kopelman P. Leptin: of mice and men? J Clin Pathol 2001 Jan;54(1):1-3

6. Ahima RS, et al. Leptin regulation of neuroendocrine systems. Front Neuroendocrinolgy 2000 Jul;21(3):263-307.

7. van Dijk G. The role of leptin in regulation of energy balance and adiposity. J Neuroendocrinol 2001 Oct;13(10):913-21.

8. Rosenbaum M et. al. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab (2002) 87:2391-2394.

9. Douyon L, Schteingart DE. Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. Endocrinol Metab Clin North Am. 2002 Mar;31(1):173-89.

10. Kennedy A et al. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab. 1997 Apr;82(4):1293-300.

11. Havel PJ et al. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. J Clin Endocrinol Metab. 1996 Dec;81(12):4406-13.

12. Doucet E et al. Changes in energy expenditure and substrate oxidation resulting from weight loss in obese men and women: is there an important contribution of leptin? J Clin Endocrinol Metab. 2000 Apr;85(4):1550-6.

13. Nicklas BJ et al. Gender differences in the response of plasma leptin concentrations to weight loss in obese older individuals. Obes Res. 1997 Jan;5(1):62-8.

14. Racette SB, Kohrt WM et al. Response of serum leptin concentrations to 7 d of energy restriction in centrally obese African Americans with impaired or diabetic glucose tolerance. Am J Clin Nutr. 1997 Jul;66(1):33-7.

15. Havel PJ et al. High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes. 1999 Feb;48(2):334-41.

16. Boden G et al. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab. 1996 Sep;81(9):3419-23.

17. Miyawaki T et al. Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans. Eur J Clin Nutr. 2002 Jul;56(7):593-600.

18. Carantoni M et al. Can changes in plasma insulin concentration explain the variability in leptin response to weight loss in obese women with normal glucose tolerance? J Clin Endocrinol Metab. 1999 Mar;84(3):869-72.

19. Zimmet P. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ. 1996 Oct 19;313(7063):965-9.

20. Tuominen et al. Leptin and thermogenesis in humans. Acta Physiol Scand. 1997 May;160(1):83-7.

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 Oct;68(4):794-801.

22. Haluzik M et al. 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 Feb-May;27(1-2):251-60.

23. Mars M et al. Leptin and insulin responses to a four-day energy-deficient diet in men with different weight history. Int J Obes Relat Metab Disord. 2003 May;27(5):574-81.

24. Pratley RE et al. Plasma leptin responses to fasting in Pima Indians. Am J Physiol. 1997 Sep;273(3 Pt 1):E644-9.

25. Okazaki T et al. Effects of mild aerobic exercise and a mild hypocaloric diet on plasma leptin in sedentary women. Clin Exp Pharmacol Physiol. 1999 May-Jun;26(5-6):415-20.

26. Mars M et al. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet. Int J Obes (Lond). 2006 Jan;30(1):122-8.

27. Kolaczynski JW. Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves. Diabetes. 1996 Nov;45(11):1511-5.

28. Kolaczynski JW. Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab. 1996 Nov;81(11):4162-5.

29. Palesty JA. The goldilocks paradigm of starvation and refeeding. Nutr Clin Pract. 2006 Apr;21(2):147-54. Review.

30. Havel PJ. Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. Proc Nutr Soc. 2000 Aug;59(3):359-71. Review.

31. Reseland JE et al. Effect of long-term changes in diet and exercise on plasma leptin concentrations. Am J Clin Nutr. 2001 Feb;73(2):240-5.

32. Romon M et al. Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake. Am J Physiol. 1999 Nov;277(5 Pt 1):E855-61.

33. van Aggel-Leijssen DP et al. Regulation of average 24h human plasma leptin level; the influence of exercise and physiological changes in energy balance. Int J Obes Relat Metab Disord. 1999 Feb;23(2):151-8.

34. Hamann A, Matthaei S. Regulation of energy balance by leptin. Exp Clin Endocrinol Diabetes. 1996;104(4):293-300. Review.

35. Ahima RS et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul 18;382(6588):250-2.

36. Meinders AE et al. Leptin. Neth J Med. 1996 Dec;49(6):247-52. Review.

37. Girard J. Is leptin the link between obesity and insulin resistance? Diabetes Metab. 1997 Sep;23 Suppl 3:16-24. Review.

38. Nedvidkova J. Leptin. Cesk Fysiol. 1997 Dec;46(4):182-8. Review.

39. Spitzweg C, Joba W, Heufelder AE. Leptin—new knowledge on the pathogenesis of obesity. Med Klin (Munich). 1998 Aug 15;93(8):478-85. Review.

40. Salidin R et al. Transient increase in obese gene expression after food intake or insulin administration. Nature. 1995 Oct 12;377(6549):527-9.

41. Maffei M, Halaas J et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995 Nov;1(11):1155-61.

42. McGarry JD. Appetite control: Does leptin lighten the problem of obesity? Curr Biol. 1995 Dec 1;5(12):1342-4. Review.

43. Wolf G. Leptin: the weight-reducing plasma protein encoded by the obese gene. Nutr Rev. 1996 Mar;54(3):91-3. Review.

44. Boden G et al. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab. 1996 Sep;81(9):3419-23.

45. Levin BE, Routh VH. Role of the brain in energy balance and obesity. Am J Physiol. 1996 Sep;271(3 Pt 2):R491-500. Review.

46. National Centre for Eating Disorders. Psychology of Dieting. 1999.

47. Rowland NE, Morien A, Li BH. The physiology and brain mechanisms of feeding. Nutrition. 1996 Sep;12(9):626-39. Review.

48. Smith SR. The endocrinology of obesity. Endocrinol Metab Clin North Am. 1996 Dec;25(4):921-42. Review.

49. Hwa JJ et al. Intracerebroventricular injection of leptin increases thermogenesis and mobilizes fat metabolism in ob/ob mice. Horm Metab Res. 1996 Dec;28(12):659-63.

50. Wing RR et al. Relationship between weight loss maintenance and changes in serum leptin levels. Horm Metab Res. 1996 Dec;28(12):698-703.

51. Martinez JA, Fruhbek G. Regulation of energy balance and adiposity: a model with new approaches. Rev Esp Fisiol. 1996 Dec;52(4):255-8. Review.

52. Schwartz MW, Seeley RJ. The new biology of body weight regulation. J Am Diet Assoc. 1997 Jan;97(1):54-8; quiz 59-60. Review.

53. Rohner-Jeanrenaud E, Jeanrenaud B. Central nervous system and body weight regulation. Ann Endocrinol (Paris). 1997;58(2):137-42. Review.

54. Blum WF. Leptin: the voice of the adipose tissue. Horm Res. 1997;48 Suppl 4:2-8. Review.

55. Weigle DS et al. Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab. 1997 Feb;82(2):561-5.

56. Jenkins AB et al. Carbohydrate intake and short-term regulation of leptin in humans. Diabetologia. 1997 Mar;40(3):348-51.

57. Arhen B et al. Regulation of circulating leptin in humans. Endocrine. 1997 Aug;7(1):1-8. Review.

58. Malmstrom R et al. Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM. Diabetologia. 1996 Aug;39(8):993-6.

59. Wisse BE et al. Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women. Am J Clin Nutr. 1999 Sep;70(3):321-30.

60. Fogteloo AJ et al. Effects of recombinant human leptin treatment as an adjunct of moderate energy restriction on body weight, resting energy expenditure and energy intake in obese humans. Diabetes Nutr Metab. 2003 Apr;16(2):109-14.

61. Coleman RA et al. Nutritional regulation of leptin in humans. Diabetologia. 1999 42(6): 639-46

62. Evans et al. Carbohydrate and fat have different effects on plasma leptin concentrations and adipose tissue leptin production. Clin Sci (Lond). 2001 May;100(5):493-8.

63. Schwartz MW et al. Model for the regulation of energy balance and adiposity by the central nervous system. Am J Clin Nutr. 1999. 69: 584-596

64. Jequier E and L Tappy. Regulation of body weight in humans. Physiol Rev. 1999. 79: 451-480

65. Levine AS and CK Billington. Do circulating leptin concentrations reflect body adiposity or energy flux? Am J Cline Nutr. 1998. 68: 761-762

66. Jequier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002. Jun;967:379-88. Review.

67. Havel, PJ. Mechanisms Regulating Leptin Production: Implications for Control of Energy Balance. American Journal of Clinical Nutrition, (Editorial) 70: 305-306, 1999.

68. Havel, PJ. Peripheral signals conveying metabolic information to the brain: short-term and long-term regulation of food intake and energy homeostasis. Exp Biol Med (Maywood) 2001;226: 963-977.

69. Havel, Peter J. Role of Adipose Tissue in Body Weight Regulation: Mechanisms Regulating Leptin Production and Energy Balance. Proceedings of the Nutrition Society 59: 359-371, 2000.

70. Heymsfield et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 1999 Oct 27;282(16):1568-75.

71. Welt C, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N. Engl. J. Med. 2004;351:987–997.

72. Reseland JE et al. Effect of long-term changes in diet and exercise on plasma leptin concentrations. Am J Clin Nutr. 2001 Feb;73(2):240-5.

73. Chu NF et al. Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men. Int J Obes Relat Metab Disord. 2001 Jan;25(1):106-14.

74. Koutsari C et al. Plasma leptin is influenced by diet composition and exercise. Int J Obes Relat Metab Disord. 2003 Aug;27(8):901-6.

75. Kondo T et al. Effect of exercise on circulating adipokine levels in obese young women. Endocr J. 2006 Apr;53(2):189-95.

76. Unal M et al. Investigation of serum leptin levels and VO2max value in trained young male athletes and healthy males. Acta Physiol Hung. 2005;92(2):173-9.

77. Ishigaki T et al. Plasma leptin levels of elite endurance runners after heavy endurance training. J Physiol Anthropol Appl Human Sci. 2005 Nov;24(6):573-8.

78. Haluzik M et al. Effect of aerobic training in top athletes on serum leptin: comparison with healthy non-athletes. Vnitr Lek. 1999 Jan;45(1):51-4. Czech.

79. Steinberg GR et al. Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle. Am J Physiol Endocrinol Metab. 2004 Jan;286(1):E57-63.

80. Frank LL et al. Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial. Obes Res. 2005 Mar;13(3):615-25.

81. Lakka TA et al. Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study. Diabetes. 2004 Jun;53(6):1603-8.

82. Dyck DJ. Leptin sensitivity in skeletal muscle is modulated by diet and exercise. Exerc Sport Sci Rev. 2005 Oct;33(4):189-94. Review.

83. Kraemer RR et al. Leptin and exercise. Exp Biol Med (Maywood). 2002 Oct;227(9):701-8. Review.

84. Rosenbaum et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest. 2005 Dec;115(12):3579-86

85. Osuna JA et al. Relationship between BMI, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006 Sep-Oct;52(5):355-61.

Submitted by DMorgan on Sun, 04/19/2009 - 1:19pm.

Enhanced Fitness and Performance and its affiliates are not responsible in any manner whatsoever for any injury or health condition that may occur through following the opinions expressed here. Consult with your physician before starting any exercise program.

Website hosted by Web Finesse Studios