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Leptin

Leptin is a hormone, produced by fat cells, that functions to maintain a lean body composition. The principal actions of leptin are:

  • Leptin regulates appetite by interacting with the hypothalamus
  • Leptin enables the body to access and utilize fat stores for energy

Leptin was discovered in 1994 by Jeffrey M. Friedman and colleagues at the Rockefeller University through the study of genetically obese mice.

While fat tissue is the primary source of Leptin, it is also produced by other body tissues including placenta, ovaries, skeletal muscle, stomach, breast tissue, pituitary and liver.

While regulating appetite and fat metabolism is its primary function, leptin also helps regulate immunity, helps maintain healthy blood pressure and supports cognitive function. In addition, high leptin levels have a variety of adverse health effects including increasing the risk of congestive heart failure, increasing the risk of heart disease and increasing cancer risk.

The Leptin Cycle

Fat tissue secretes leptin. High leptin levels signal the hypothalamus to decrease appetite, decrease food intake and reduce fat accumulation. So, normally, lean people have low leptin levels and fat people have high leptin levels. As the amount of stored fat increases, so do the leptin levels. So, why isn't the rising leptin level triggering weight loss?

The answer is leptin resistance. The neurons in the hypothalamus lose their sensitivity to leptin resulting in a lack of satiety and apatite suppression. As the size and number of fat cells increase with weight gain, they pump more and more leptin into the circulation in an attempt to send the message to the brain that fat stores are adequate, and appetite needs to be reined in.

Inadequate receptor sensitivity results in diminished responsiveness, which has two unfortunate results. First, normal fatty acid metabolism within the fat cells significantly declines and, the fat cells decrease their absorption of free fatty acids from the circulation. The resulting excess of fatty acids floating in the bloodstream causes insulin resistance in peripheral tissues like muscle.

As with leptin-resistant fat cells, insulin-resistant muscle cells lose their responsiveness to insulin. As a result, glucose molecules are blocked from entering muscle tissue, causing blood sugar to rise. The liver senses hyperglycemia and liver cells respond by breaking down the rogue sugar molecules and transforming them into more free fatty acids. In turn, the additional free fatty acids contribute to increased fat stores, increased leptin production, escalating resistance, and the vicious cycle continues to snowball.

What Causes Leptin Resistance?

Consuming excess calories causes fat deposition which raises leptin levels. Reduced physical activity decreases calorie metabolism which reduces fat metabolism. Chronically high leptin levels causes leptin resistance. In short, over eating and lack of exercise causes leptin resistance. So what causes over eating? It is a combination of factors including:

  • Eating for stress relief or comfort rather than hunger
  • Poor food choices
  • Life style choices
  • Poor habits
  • High Fructose Foods

Fructose and Leptin Resistance

In addition to this well established relationship, recent research suggests that the consumption of large amounts of fructose causes leptin resistance and elevated triglycerides in animals. A similar mechanism likely exists in humans. Fructose is widely used as a sweetener in many foods. On the label it may be called fructose, corn syrup or high fructose corn syrup. Fructose is also the natural sugar found in honey, fruits and berries. The unanswered questions are:

  • How much fructose is required to contribute to leptin resistance in humans?
  • Is there a difference between the fructose synthesized from corn and fructose from natural honey, fruits and berries?

The information on this is unclear at this time, requiring further research. We do know that our ancestors consumed natural honey, fruits and berries when they were available, so it is likely that consuming these natural foods in moderation is safe and healthful. We also know that fructose derived from corn products is very common and abundant in many processed foods. The conservative approach to this is to read labels and avoid fructose adulterated foods.

How to Correct Leptin Resistance

Reducing leptin resistance requires reducing leptin levels which requires reducing fat which requires weight loss which requires calorie restriction and exercise. Both calorie restriction and exercise cause a shift in metabolism and several hormones. Resetting the hypothalamic regulation system may not occur quickly. Persistent and sustained lifestyle change rather than short term or yo-yo dieting is required. Fortunately, improvement in the risk factors for Metabolic Syndrome and improvement in insulin resistance occur much more quickly than significant weight loss.

Leptin related Supplements

Body Trim and Appetite Control

Leptin References

Click to Expand References

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (December 1994). "Positional cloning of the mouse obese gene and its human homologue". Nature 372 (6505): 425-32. doi:10.1038/372425a0. PMID 7984236.

http://en.wikipedia.org/wiki/Leptin, accessed Feb. 2010

Leptin and Weight Loss: The Hormonal Key to Fat Reduction and Heart Health By Kimberly Pryor from: http://vrp.com/articles.aspx?ProdID=art1862&zTYPE=2, accessed Feb. 2010

Fantuzzi G, Sennello JA, Batra A, Fedke I, Lehr HA, Zeitz M, Siegmund B. Defining the role of T cell-derived leptin in the modulation of hepatic or intestinal inflammation in mice. Clin Exp Immunol. 2005 Oct;142(1):31-8.

Mukherjee R, Villarreal D, Reams GP, Freeman RH, Tchoukina I, Spear RM. Leptin as a common link to obesity and hypertension. Timely Top Med Cardiovasc Dis. 2006 Jan 2;10:E1.

Farr SA, Banks WA, Morley JE. Effects of leptin on memory processing. Peptides. 2005 Nov 14;

Anim-Nyame N, Domoney C, Panay N, Jones J, Alaghband-Zadeh J, Studd JW. Plasma leptin concentrations are increased in women with premenstrual syndrome. Hum Reprod. 2000 Nov;15(11):2329-32.

Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol. 1998 Apr;157(1):75-9.

Perego L, Pizzocri P, Corradi D, Maisano F, Paganelli M, Fiorina P, Barbieri M, Morabito A, Paolisso G, Folli F, Pontiroli AE. Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery: a potential role for leptin in mediating human left ventricular hypertrophy. J Clin Endocrinol Metab. 2005 Jul;90(7):4087-93. Epub 2005 Apr 26.

Gomez-Ambrosi J, Salvador J, Paramo JA, Orbe J, de Irala J, Diez-Caballero A, Gil MJ, Cienfuegos JA, Fruhbeck G. Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors. Clin Biochem. 2002 Jun;35(4):315-20.

"Fructose Sets Table For Weight Gain Without Warning". Science News. Science Daily. 2008-10-19. http://www.sciencedaily.com/releases/2008/10/081016074701.htm. Accessed Feb 2010.

Vasselli JR (November 2008). "Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance. Focus on "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding," by Shapiro et al.". Am. J. Physiol. Regul. Integr. Comp. Physiol. 295 (5): R1365-9. doi:10.1152/ajpregu.90674.2008. PMID 18784330.

Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ (November 2008). "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding". Am. J. Physiol. Regul. Integr. Comp. Physiol. 295 (5): R1370-5. doi:10.1152/ajpregu.00195.2008. PMID 18703413.


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