Leptin hormone role of in obesity and food intake
December 19 2015 by
Ray Sahelian, M.D.

Leptin is a hormone secreted from adipocytes (fat cells) and functions to suppress appetite and increase energy expenditure. Leptin is a proinflammatory cytokine. In contrast, ghrelin, a protein known to trigger feeling of hunger, increases during periods of fasting and decreases after a meal. The discovery of leptin in the 1990s created a furor, because when injected into rodents it caused them to eat less and lose weight. As of 2011, there is no leptin supplement available over the counter.

Role of the hormone
Leptin has a wide range of effects on physiological functions related to the regulation of body energy balance. Many of leptin's effects are mediated through neuropeptide-containing neurons and neuropeptide receptors in the hypothalamus. The melanocortin system includes both agonist (alpha-melanocyte stimulating hormone, alphaMSH) and antagonist peptides (agouti related peptide, AGRP). Increased melanocortin receptor stimulation following leptin administration plays an important role in leptin-induced hypophagia and increased sympathetic nervous system activity and is partly responsible for leptin -induced weight loss. However, melanocortins do not appear to mediate some of the more striking centrally-mediated effects of leptin on adipose tissue, including adipose tissue apoptosis, that lead to the extensive depletion of fat.

Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered.

Natural supplements that help with appetite control
There are several supplements that have an influence on appetite including the following:
Hoodia reduces appetite in some people
Green Tea extract
Garcinia cambogia is an herb that has hydrocytric acid
5-HTP which converts into serotonin
Acetylcarnitine is the acetyl form of carnitine.

Dietary supplement over the counter
Is there a safe or effective leptin supplement available or soon to be on the market?

Where can I buy a leptin supplement?
   To the best of my knowledge, such a supplement is not currently available. Leptin is a hormone and I would think the FDA may not allow such a hormone to be sold over the counter. Therefore, I doubt if there are legitimate over the counter leptin diet pills available.

I came across a product that claims to control leptin. Is there research on such pills that control it? Is there an herb that can lower leptin levels or prevent its resistance?
   I have not seen any studies on leptin control supplements that have been evaluated in humans. Therefore, the claims of control or resistance supplements appear to be misleading at this time. There may be herbs or supplements that lower leptin levels, but we don't have the research at this time to support such claims.

Leptin given to obese patients reduces appetite
Giving leptin hormone to morbidly obese volunteers de-activates their brain's response to tasty food. When given leptin hormone, the centers in the brain involved in self-control are more activated. When given leptin injections, there is activation of the cerebellum -- a section of the brain at the base of the head.

Leptin, diet, obesity, and heart disease
Emerging evidence from both animal and human studies indicates that leptin may play an important role in obesity -related cardiovascular disease. Besides modulating appetite and metabolism, leptin has also been shown to increase sympathetic nerve activity, stimulate generation of reactive oxygen species, upregulate endothelin-1 production and potentiate platelet aggregation. These effects of leptin may contribute to hypertension, endothelial dysfunction and atherosclerosis in obese individuals. Better understanding the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance.
   Recent observations suggest that the cardiovascular actions of leptin may help explain the link between excess fat mass and cardiovascular diseases. Leptin is an adipocyte-derived hormone that acts in the central nervous system to promote weight loss by decreasing food intake and increasing metabolic rate. Leptin hormone causes a significant increase in overall sympathetic nervous activity, which appears to be due to direct hypothalamic effects and is mediated by neuropeptide systems such as the melanocortin system and corticotropin-releasing hormone. Renal sympathoactivation to leptin is preserved in the presence of obesity, despite resistance to the metabolic effects of leptin. Such selective leptin resistance, in the context of circulating hyperleptinemia, could predispose to obesity-related hypertension.

Atherosclerosis. March 2014. Leptin and coronary heart disease: A systematic review and meta-analysis. Leptin, an adipose tissue-derived hormone, plays a central role in regulating human energy homeostasis. The role of leptin in regulating blood pressure, activating the sympathetic nervous system, insulin resistance, platelet aggregation, arterial thrombosis, angiogenesis, and inflammatory vascular responses suggests that leptin may have a close relationship with the development of coronary heart disease (CHD). However, no conclusive data are available to determine the association between leptin and CHD. Although the associations of leptin and CHD were not statistically significant both in male and female overall, males with high levels of leptin should be paid more attention to. Our findings highlight the need for additional well-designed and gender-specific prospective studies to evaluate the role of leptin on the development of CHD.

Exercise influence
Plasma leptin is associated with satiety and that it stimulates lipid metabolism, and increases energy expenditure. These effects implicate leptin as a major regulator of energy homeostasis, which may serve to limit excess energy storage. As plasma leptin concentrations are tightly coupled with fat mass in humans, decreases in adipose mass with weight loss coincide with decreased concentrations of circulating leptin. However, due to many confounding factors, the effects of exercise on circulating leptin are less clear. The data from investigations examining single exercise bouts suggest that serum leptin concentrations are unaltered by short duration (41 minutes or less), non-exhaustive exercise, but may be affected by short duration, exhaustive exercise. More convincingly, studies investigating long duration exercise bouts indicate that serum leptin concentrations are reduced with exercise durations ranging from one to multiple hours. These findings raise speculation that exercise-associated reductions in leptin may be due to alterations in nutrient availability or nutrient flux at the level of the adipocytes, the primary site of leptin production and secretion.

Hormonal effects
Leptin hormone plays a critical role in the control of appetite and energy balance, with mutations in the genes encoding the hormone or its receptor leading to profound obesity in both rodents and man. Leptin regulates appetite primarily through an interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic peptides such as proopiomelanocortin.
   The presence of higher leptin levels in boys with pubertal gynecomastia indicates that leptin hormone may be involved in the pathogenesis of pubertal gynecomastia. The role of circulating leptin in pubertal gynecomastia is probably related to increase in estrogen and/or estrogen/ androgen ratio by the stimulating effect of leptin on aromatase enzyme activity in both adipose and breast tissues, or a direct growth stimulating effect of leptin on mammary epithelial cells, or increase in sensitivity of breast epithelial cells to estrogen with inducing functional activation of estrogen receptors by leptin in breast tissue.

Elderly and seniors
Some healthy elderly individuals experience a decrease in appetite and consequently eat less than they normally ate when they were younger. Part of this decrease in appetite may be due to hormone alterations that reduce hunger and increase feelings of fullness. The elderly have higher leptin levels under fasting conditions than younger individuals, but both groups have similar levels of the hormone after eating. American Journal of Clinical Nutrition, May 2006.

High levels of leptin hormone, an inflammatory compound produced by body fat, may raise the risk of asthma in premenopausal women. Because previous reports have linked leptin levels with asthma in children, Dr. Akshay Sood, from Southern Illinois University School of Medicine in Springfield, and colleagues decided to see if it held true in adults as well. Using data from 5876 participants in the Third National Health and Nutrition Examination Survey, the researchers found that elevated leptin levels did, in fact, correlate with asthma in adults. This association was stronger in women than in men and stronger in premenopausal women than in postmenopausal women. There appears to be evidence from animal studies that leptin plays a pro-inflammatory role in the airways. Source: Thorax, April 2006.

Brain function
The hormone leptin signals information regarding the status of fat stores to hypothalamic nuclei, which in turn control feeding behavior and body weight. However, leptin and its receptor are widely expressed in many extra-hypothalamic brain regions, including hippocampus, brain stem and cerebellum. Leptin has other neuronal functions that are unrelated to its effects on energy homeostasis. Leptin-deficient rodents display abnormal brain development and leptin actively participates in the development of the hypothalamus. In the hippocampus, leptin is a potential cognitive enhancer as genetically obese rodents with dysfunctional leptin receptors display impairments in hippocampal synaptic plasticity. Direct administration of leptin into the hippocampus can facilitate hippocampal LTP (long-term potentiation) in vivo and improve memory processing in mice.

Menstrual cycle
A lack of leptin contributes to the absence of menstrual periods in women with extremely low levels of body fat, but treatment with a synthetic form of the hormone may restore both the menstrual cycle and fertility.

Pancreatic function
Diabetes Care. Feb 4 2014. Effects of Leptin Replacement Therapy on Pancreatic β-Cell Function in Patients With Lipodystrophy. Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy. In a prospective, open-label, currently ongoing study we studied the effects of leptin replacement on β-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. β-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT. There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, β-cell glucose sensitivity, rate sensitivity, or insulin clearance. In contrast to the suppressive effects of leptin on β-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.

Psoriasis skin disease
People with psoriasis have higher levels of the hormone leptin, which regulates food intake, body weight, and fat stores and is also thought to play a role in immune and inflammatory processes. Those elevated leptin levels may in turn make them more likely to become obese or develop high blood pressure, diabetes, and other heart disease risk factors.

Leptin, diet, and hormone studies
Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit.
Neuron. 2005. Department of Pathology and Cell Biology in the Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, New York
Recently developed therapeutics for obesity, targeted against cannabinoid receptors, result in decreased appetite and sustained weight loss. Prior studies have demonstrated CB1 receptors (CB1Rs) and leptin modulation of cannabinoid synthesis in hypothalamic neurons. Here, we show that depolarization of perifornical lateral hypothalamus (LH) neurons elicits a CB1R-mediated suppression of inhibition in local circuits thought to be involved in appetite and "natural reward." The depolarization-induced decrease in inhibitory tone to LH neurons is blocked by leptin. Leptin inhibits voltage-gated calcium channels in LH neurons via the activation of janus kinase 2 (JAK2) and of mitogen-activated protein kinase (MAPK). Leptin-deficient mice are characterized by both an increase in steady-state voltage-gated calcium currents in LH neurons and a CB1R-mediated depolarization-induced suppression of inhibition that is 6-fold longer than that in littermate controls. Our data provide direct electrophysiological support for the involvement of endocannabinoids and leptin as modulators of hypothalamic circuits underlying motivational aspects of feeding behavior. Leptin in food.

Plasma leptin concentrations in postmenopausal women with osteoporosis.
Endocrine Research. 2005.
Osteoporosis is less common in obese individuals with increased bone mineral density (BMD) and plasma leptin concentrations. The aim of this study was to determine the correlation between leptin levels and BMD in postmenopausal women. The study consisted of 90 postmenopausal women with a mean age of 53.45 +/- 0.87 years who visited our outpatient clinic for the evaluation of BMD. From this study we conclude that circulating plasma leptin hormone level does not have a significant direct influence on bone mass in postmenopausal women.

Therapeutic Effect of Puerarin on Non-Alcoholic Rat Fatty Liver by Improving Leptin Signal Transduction through JAK2/STAT3 Pathways.
Am J Chin Med. 2009. Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
In order to investigate the mechanism of the therapeutic effect of puerarin on non-alcoholic fatty liver disease, a non-alcoholic fatty disease male rat model was induced by a high fat diet, all rats were randomly divided into a blank group, model group, simavastatin group and puerarin group. All the results demonstrated that puerarin can exhibit therapeutic effect on non-alcoholic fatty liver disease by improving leptin signal transduction through JAK2/STAT3 pathways.

Does hoodia extract influence leptin hormone levels?
   I have not come across research regarding the influence of a hoodia supplement on this hormone level, so I don't know.

Is there leptin in food?
   I don't think there's any in food but I'm not sure.