Researchers have been trying to identify a specific cause for obesity for over 50 years. In 1950 they discovered a genetic defect in mice that led to morbid obesity. The researchers noted that the mice weighed up to 3 times that of normal mice and ate constantly. When the circulation of obese mice was connected to that of normal mice, the obese mice lost weight, confirming that the obese mice were deficient in a blood-borne protein that regulated hunger and body weight. It was not until 1995 when this protein leptin was identified. Since the initial discovery of leptin 15 years ago have 8,000 scientific papers been published on this topic.
The hormone leptin is now considered to be the primary regulator of
- appetite and
in humans. Leptin is primarily secreted from fat tissue. Small amounts of leptin are althogh secreted from the stomach and the placenta. Since greater amounts of fat tissue result in a greater circulating leptin concentration, overweight and obese people have higher leptin levels than leaner people . After the secretion binds leptin to receptors that causes hormonal signals to be released that limit hunger and thus control food intake .
The greatest concentration of leptin receptors is found in the hypothalamus of the brain. The hypothalamus plays a vital role in body weight regulation. The effects of leptin on body weight are the result of several mechanisms in the hypothalamus that regulate hunger, body temperature, vitamin and nutrient synthesis.
Leptin has numerous effects on the body related to metabolism and hunger and include:
- Counteracts the effects of proteins that promote feeding
- Inhibits hunger
- Increases metabolism and energy expenditure
- Stimulates fat burning in the liver and muscles
Consistently elevated leptin levels impair the function of leptin receptors, thereby requiring greater leptin secretion to produce the same effect. This is a similar mechanism as that of the diabetic who produces more and more insulin because the receptors in the liver have become desensitized over time.
The exact cause by which leptin affects metabolism is yet to be clearly understood. Leptin levels in the body can be changed and they respond rapidly to changes in body fat . Losing weight decreases leptin levels in the body. Several studies have shown that even in subjects that experienced similar weight loss through dieting, those on a low carbohydrate diet had a greater leptin decrease versus subjects on a low fat diet [4-6]. Furthermore, subjects with the greatest central abdominal fat loss has the greatest decreases in circulating leptin .
Obesity and the chronic diseases caused by obesity are rapidly becoming a public health crisis world wide. In fact, obesity has recently been declared a worldwide epidemic by the World Health Organization . In the United States alone, one quarter of the population is overweight and one quarter are obese. Tremendous amounts of research are conducted in order to understand the mechanisms of obesity and billions of dollars are spent each year on weight loss products, vitamins, liquid vitamins and herbs, all in a desperate attempt to loose skin weight.
Obesity results when caloric intake exceeds caloric expenditure. Although this concept of weight gain is quite simplistic, energy balance and body weight regulation are complex functions that are controlled, in part, by genes and hormones. The set-point theory states that body weight is regulated around a very narrow range, often within 10-15 pounds. This theory was developed after multiple studies showed that people who lost or gained a considerable amount of weight usually returned to their starting weight over time.
The body adapts to under- or overeating by changing three mechanisms:
- resting metabolism
- metabolism during activity
- metabolism from digestion of food
For example, during weight loss, the body will decrease metabolism, which will result in fewer calories expended in a day. This will make it more difficult to lose more weight, thus staying within the boundaries of the set-point weight range. For some time now this theory has been widely accepted, although the exact mechanism by which this feat was accomplished has been unclear.
Given the emerging details of the role of leptin in weight management, the use of leptin injections as a therapy to aid weight loss has generated much interest. It is known that leptin administration promotes fat loss, but has no effect on lean tissue mass. However, large scale human trials have not been conducted and commercial interest in researching this hormone to be marketed for weight loss has waned recently because of the potential side effects. Not only does leptin impact metabolism and hunger, leptin also plays key roles in immunity, lung function, bone development and reproduction. Animal studies to date have shown that the risk of leptin therapy does not currently warrant the use of leptin as a treatment for obesity in humans. While we continue to research the reasons for staggering obesity rates, it is agreed by the majority that vitamin rich whole foods should be the mainstay of a healthy diet.
- Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, et al.: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295.
- Schwartz MW: Brain pathways controlling food intake and body weight. Exp Biol Med (Maywood) 2001;226:978-981.
- Lurnell JQ, Cummings D, Weigle DS: Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity. Int J Obes (Lond) 2007;31:385-389.
- de Luis DA, Aller R, Izaola O, Gonzalez Sagrado M, Bellioo D, Conde R: Effects of a low-fat versus a low-carbohydrate diet on adipocytokines in obese adults. Horm Res 2007;67:296-300.
- Cardillo S, Seshadri P, Iqbal N: The effects of a low-carbohydrate versus low-fat diet on adipocytokines in severely obese adults: three-year follow-up of a randomized trial. Eur Rev Med Pharmacol Sci 2006;10:99-106.
- Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP: Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med 2005;142:403-411.
- Miller LE, Volpe JJ, Coleman-Kelly MD, Gwazdauskas FC, Nickols-Richardson SM: Anthropometric and leptin changes in women following different dietary approaches to weight loss. Obesity (Silver Spring) 2009;17:199-201.
- Huang L, Li C: Leptin: a multifunctional hormone. Cell Res 2000;10:81-92.