Leptin and its Effects on Weight Loss
Weight loss is a goal that many wish to achieve for a number of reasons. Some may wish to look better and some may just want to lose body fat to reduce their risk of cardiovascular disease. Obesity is a worldwide public health problem that can bring with it numerous health problems. In fact, data shows that a body weight that is 20% more than the ideal weight can reduce life expectancy.1 This is largely because people who are obese are at a higher risk of developing cardiovascular risk factors such as hypertension and diabetes.
While the concept of weight loss appears simple, there are a number of factors that can play a part in successful weight loss. One such factor is Leptin – a mediator that can induce weight loss. In this article, we shall explore the relationship between Leptin and weight loss, particularly concentrating on leptin resistance and sensitivity.
What is Leptin?
Leptin is a complex protein molecule that is generated from the adipocytes within the human body. The word ‘leptin’ is derived from the Greek word ‘leptos’ meaning ‘thin’. As a hormone, leptin plays an important role in the regulation of food intake, expenditure of energy and in neuro-endocrine function. In addition to this, it also reduces the amount of adipose tissue within the skeletal muscle and liver.2
Leptin was initially identified by Zhang et al along with the human obese (OB) gene in 1994.3 It acts through OBR (also called leptin receptor) which is located in numerous sites such as the brain, vasculature, placenta and the stomach. Once released by the adipose tissue, leptin crosses the blood brain barrier and binds to leptin receptors on the hypothalamus, thus acting as a signalling hormone that regulates the body’s energy requirement and stores through the release of a number of anorexigenic and orexigenic neuro-peptides. In other words, it reduces overall food intake and maintains ideal body weight by increasing energy expenditure.4
Leptin and body weight
When leptin is secreted from the adipose tissue from subjects with normal body fat levels, it actively plays a part in maintaining body weight and keeping it low. However, in obese subjects, leptin resistance develops which can make weight loss even harder.
The relationship between leptin and body weight has been long studied. In children who have congenital leptin deficiency, Montague et al demonstrated that they had normal birth weight, but as they grew older they had a significant rise in body mass index that was related to excessive food intake and impairment in satiety.5 Other studies have shown low leptin levels to be associated with a higher prevalence of obesity, an effect that was reversed with leptin treatment.6
The concept of leptin resistance
An interesting observation in obese individuals is the presence of high levels of leptin in the circulation and within the adipocytes (the opposite would be expected as previously mentioned). Treatment of these obese individuals did not alter their weight in any way, leading to the development of the concept of leptin resistance.7 The physiology behind the development of leptin resistance lies with overstimulation and damage to the hypothalamus by constantly elevated leptin levels that is stimulated by over-eating.8 The damage to the hypothalamus results in it becoming less sensitive to leptin, ultimately leading to high levels of leptin levels being sustained.
Studies have shown that leptin resistance may develop due to problems with its transport across the blood brain barrier. In obese individuals, the levels of leptin within the cerebrospinal fluid are a lot lesser than the levels in the plasma.9 Whether this defective transport occurs only after obesity sets in is unclear, though research has shown this to be likely.10
Besides the above mentioned reasons, leptin resistance may develop due to a change in sensitivity of the leptin receptors located within the hypothalamus. However, evidence to the contrary exists and further studies are required to confirm this hypothesis as a likely possibility.
Leptin and weight loss
In order to lose weight, leptin sensitivity needs to be restored. The use of recombinant leptin administered exogenously has been studied in both lean and obese individuals. While weight loss was seen in both groups, there appeared to be a relative leptin resistance in obese individuals, with resistance levels increasing with levels of adiposity.11 Naturally occurring leptin within the body is regulated to some extent by other factors within. For example, ensuring a good night’s sleep is important in regulating leptin levels. It has been demonstrated that the leptin levels are at their peak at night (similar to melatonin), and altering sleep patterns can alter leptin levels and result in weight gain.12
These days, commercially available leptin-lowering supplements are being sought after to lose weight. Studies have shown that melatonin supplementation is associated with a reduction in leptin levels and is related to the response of the pineal gland to melatonin.13 Supplements such as L-carnitine14 and conjugated linoleic acid (CLA)15 have also been shown to reduce leptin levels, increase leptin sensitivity and aid weight loss.
Leptin has been demonstrated to play an important role in weight control and is now being explored further as a part of weight loss plans. From the available evidence, lowering the levels of leptin is associated with weight loss, and this may be achieved by using the mentioned supplements on a regular basis.
1. Harris, T. et al. Body mass index and mortality among non smoking older persons: the Framingham Heart Study. J. Am. Med. Assoc. 259, 1520–1524 (1988).
2. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763–70.
3. 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
4. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weightreducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–546.
5. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S. Congenital leptin deﬁciency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903–908
6. Farooqi IS, Keogh JM, Kamath S, Jones S, Gibson WT, Trussell R, Jebb SA, Lip GY, O’Rahilly S. Partial leptin deﬁciency and human adiposity. Nature 2001; 414: 34–35.
7. Considine RV, Considine EL, Williams CJ, Hyde TM, Caro JF. The hypothalamic leptin receptor in humans: identiﬁcation of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. Diabetes 1996; 45: 992–994.
8. Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF. Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab 1996; 81: 4162–4165.
9. Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte D Jr. Cerebrospinal ﬂuid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med 1996; 2: 589–593.
10. Levin BE, Dunn-Meynell AA, Banks WA. Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset. Am J Physiol Regul Integr Comp Physiol 2004; 286: R143–R150
11. Heymsfield, Steven B., et al. “Recombinant leptin for weight loss in obese and lean adults.” JAMA: the journal of the American Medical Association 282.16 (1999): 1568-1575.
12. Spiegel K, Leproult R, Van Cauter E. [Impact of sleep debt on physiological rhythms] [Article in French]. Rev Neurol (Paris). 2003 Nov;159(11 Suppl):6S11-20.
13. Canpolat S, Sandal S, Yilmaz B, Yasar A, Kutlu S, Baydas G, Kelestimur H. Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat. Eur J Pharmacol. 2001 Sep 28;428(1):145-8.
14. Lofgren IE, Herron KL, West KL, Zern TL, Brownbill RA, Ilich JZ, Koo SI, Fernandez ML. Weight loss favorably modifies anthropometrics and reverses the metabolic syndrome in premenopausal women. J Am Coll Nutr. 2005 Dec;24(6):486-93.
15. Belury MA, Mahon A, Banni S. The conjugated linoleic acid (CLA) isomer, t10c12-CLA, is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus. J Nutr. 2003 Jan;133(1):257S-260S.