Script error: No such module "Distinguish". Template:PBB Template:Infobox protein family Leptin (Greek λεπτός (leptos) meaning "thin") is a 16-kDa adipokine that plays a key role in regulating energy intake and expenditure, including appetite and hunger, metabolism, and behavior. It is one of the most important adipose-derived hormones. Leptin functions by binding to the leptin receptor. The Ob(Lep) gene (Ob for obese, Lep for leptin) is located on chromosome 7 in humans.
- 1 Discovery
- 2 Biosynthesis
- 3 Physiology
- 4 Function
- 5 Clinical significance
- 6 Mechanism of action
- 7 Metreleptin
- 8 See also
- 9 References
- 10 Further reading
- 11 External links
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Template:Peacock Leptin is a hormone made by fat tissue that acts on the brain to regulate food intake and body weight. The existence of a hormone regulating food intake and body weight was hypothesized based on studies of mutant obese mice that arose at random within a mouse colony at the Jackson Laboratory in 1950. Mice homozygous for the ob mutation (ob/ob) ate voraciously and were massively obese. In the 1960s, a second mutation causing obesity and a similar phenotype was identified by Douglas Coleman, also at the Jackson Laboratory, and was named diabetes (db), as both ob/ob and db/db were obese. Leibel and Friedman reported the mapping of the ob gene in 1990. Consistent with Coleman’s and Leibel's hypothesis, several subsequent studies from Leibel's and Friedman’s labs and other groups confirmed that the ob gene encoded a novel hormone that circulated in blood and that could suppress food intake and body weight in ob and wild type mice, but not in db mice. In 1994, with the ob gene isolated, Friedman reported the discovery of the gene and named this new hormone leptin. After a meeting where Friedman met Nobel Prize winner, Frenchman Roger Guillemin, he got a letter from him that he recalls saying, “I really liked what you had to say, but I have one quibble: you refer to these as obesity genes, but I think they are lean genes because the normal allele keeps you thin. But calling them lean genes sounds awkward. The nicest sounding root for thin is from Greek, so I propose you call ob and db ‘lepto-genes.’” So Friedman remembered Guillemin’s suggestion, and the hormone was named leptin. Leptin was the first fat cell-derived hormone to be discovered. Subsequent studies confirmed that the db gene encoded the leptin receptor and that it was expressed in the hypothalamus, a region of the brain known to regulate food intake and body weight.
The identification of leptin is considered to be a major scientific advance. While Coleman and Friedman have been awarded numerous prizes acknowledging their roles in its discovery, including the Gairdner Foundation International Award (2005), the Shaw Prize (2009), the Lasker Award, the BBVA Prize and the King Faisal International Prize, Leibel has not received the same level of fame from the discovery because he was omitted as a co-author of a scientific paper published by Friedman that reported the discovery of the gene. The various theories surrounding Friedman’s omission of Leibel and others as co-authors of this important paper have been presented in a number of publications, including Ellen Ruppel Shell’s 2002 book The Hungry Gene.
The discovery of leptin has also been written about in a series of books including Fat: Fighting the Obesity Epidemic by Robert Pool, The Hungry Gene by Ellen Ruppel Shell, and Rethinking Thin: The New Science of Weight Loss and the Myths and Realities of Dieting by Gina Kolata. Fat: Fighting the Obesity Epidemic and Rethinking Thin: The New Science of Weight Loss and the Myths and Realities of Dieting review the work in the Friedman laboratory that led to the cloning of the ob gene, while The Hungry Gene draws attention to the contributions of Leibel.
Human leptin is a protein of 167 amino acids. It is manufactured primarily in the adipocytes of white adipose tissue, and the level of circulating leptin is proportional to the total amount of fat in the body.
In addition to white adipose tissue—the major source of leptin—it can also be produced by brown adipose tissue, placenta (syncytiotrophoblasts), ovaries, skeletal muscle, stomach (the lower part of the fundic glands), mammary epithelial cells, bone marrow, pituitary, and liver.
The discovery of leptin has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level, which has been widely validated in several experimental rodent obesity models; nevertheless adequate proof of its equivalent operation in humans remains elusive. Leptin is a peptide hormone expressed, synthesized and secreted by adipose tissue in proportion to its mass. This hormone circulates in blood and acts on the hypothalamus to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. This physiological system ensures that total energy stores are stably maintained within a relatively narrow range. The identification of a physiologic system that controls energy balance also establishes a biologic basis for obesity. Leptin also regulates many other physiologic systems and plays a critical role in the adaptive response to starvation. Leptin circulates in blood in free form and bound to proteins. Serum leptin levels are higher between midnight and early morning which could have an effect in suppressing appetite during the night while sleeping. The diurnal rhythm of plasma leptin can be modified by meal-timing indicating that plasma leptin is entrained to meal timing.
Leptin acts on receptors in the hypothalamus of the brain, where it inhibits appetite
- counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus)
- counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC)
- promoting the synthesis of α-MSH, an appetite suppressant.
This appetite inhibition is long-term, in contrast to the rapid inhibition of eating by cholecystokinin (CCK) and the slower suppression of hunger between meals mediated by PYY3-36. The absence of leptin (or its receptor) leads to uncontrolled food intake and resulting obesity. Several studies have shown fasting or following a very-low-calorie diet (VLCD) lowers leptin levels. In the short-term, leptin might be an indicator of energy balance. This system is more sensitive to starvation than to overfeeding; leptin levels change more when food intake decreases than when it increases. The dynamics of leptin due to an acute change in energy balance may be related to appetite and eventually to food intake. Although this is a new hypothesis, some data already support it.
Controversy is ongoing regarding the regulation of leptin by melatonin during the night. One research group suggested increased levels of melatonin caused a downregulation of leptin. However, in 2004, Brazilian researchers found melatonin to increase leptin levels in the presence of insulin, therefore causing a decrease in appetite during sleeping. Still other researchers in Belgium found partial sleep deprivation to be associated with decreased leptin levels
Mice with type 1 diabetes treated with leptin alone or in conjunction with insulin did better (blood sugar did not fluctuate as much; cholesterol levels decreased; less body fat formed) than those treated with insulin alone, raising the prospect of a new treatment for diabetes.
- Leptin circulates at levels directly proportional to body fat.
- It enters the central nervous system in proportion to its plasma concentration.
- Its receptors are found in brain neurons involved in regulating energy intake and expenditure.
- It controls food intake and energy expenditure by acting on receptors in the mediobasal hypothalamus.
Interaction with amylin
Coadministration of two neurohormones known to have a role in body weight control, amylin (nutrient/glucose appearance inhibitor produced by β cells in the pancreas) and leptin (produced by fat cells), results in sustained, fat-specific weight loss in a leptin-resistant animal model of obesity.
Leptin binds to neuropeptide Y (NPY) neurons in the arcuate nucleus in such a way as to decrease the activity of these neurons. Leptin signals the brain that the body has had enough to eat, producing a feeling of satiety. Moreover, this fullness hormone may make it easier for people to resist the temptation of foods high in calories.
Circulating leptin levels give the brain input regarding energy storage, so it can regulate appetite and metabolism. Leptin works by inhibiting the activity of neurons that contain neuropeptide Y (NPY) and agouti-related peptide (AgRP), and by increasing the activity of neurons expressing α-melanocyte-stimulating hormone (α-MSH). The NPY neurons are a key element in the regulation of appetite; small doses of NPY injected into the brains of experimental animals stimulates feeding, while selective destruction of the NPY neurons in mice causes them to become anorexic. Conversely, α-MSH is an important mediator of satiety, and differences in the gene for the receptor at which α-MSH acts in the brain are linked to obesity in humans.
A very small group of humans possesses homozygous mutations for the leptin gene, leading to a constant desire for food and resulting in severe obesity. This condition can be treated somewhat successfully by the administration of recombinant human leptin. However, extensive clinical trials using recombinant human leptin as a therapeutic agent for treating obesity in humans have been inconclusive because only the most obese subjects who were given the highest doses of exogenous leptin produced statistically significant weight loss. Large and frequent doses are needed to provide only modest benefit because of leptin’s low circulating half-life, low potency, and poor solubility. Furthermore, these injections caused some participants to drop out of the study due to inflammatory responses of the skin at the injection site. Some of these problems can be alleviated by a form of leptin called Fc-leptin, which takes the Fc fragment from the immunoglobulin gamma chain as the N-terminal fusion partner and follows it with leptin. This Fc-leptin fusion has been experimentally proven to be highly soluble, more biologically potent, and contain a much longer serum half-life. As a result, this Fc-leptin was successfully shown to treat obesity in both leptin-deficient and normal mice, although studies have not been undertaken on human subjects. This makes Fc-leptin a potential treatment for obesity in humans after more extensive testing.
The role of leptin/leptin receptors in modulation of T cell activity in immune system was shown in experimentation with mice. It modulates the immune response to atherosclerosis, of which obesity is a predisposing factor.
In some epidemiological studies, hyperleptinemia is considered as a risk factor. However, a few animal experiments demonstrated systemic hyperleptinemia produced by infusion or adenoviral gene transfer decreases blood pressure in rats.
Lung surfactant activity
In fetal lung, leptin is induced in the alveolar interstitial fibroblasts ("lipofibroblasts") by the action of PTHrP secreted by formative alveolar epithelium (endoderm) under moderate stretch. The leptin from the mesenchyme, in turn, acts back on the epithelium at the leptin receptor carried in the alveolar type II pneumocytes and induces surfactant expression, which is one of the main functions of these type II pneumocytes.
In mice, leptin is also required for male and female fertility. It has a lesser effect in humans. In mammals such as humans, ovulatory cycles in females are linked to energy balance (positive or negative depending on whether a female is losing or gaining weight) and energy flux (how much energy is consumed and expended) much more than energy status (fat levels). When energy balance is highly negative (meaning the woman is starving) or energy flux is very high (meaning the woman is exercising at extreme levels, but still consuming enough calories), the ovarian cycle stops and females stop menstruating. Only if a female has an extremely low body fat percentage does energy status affect menstruation. Some studies have indicated leptin levels outside an ideal range can have a negative effect on egg quality and outcome during in vitro fertilization. Leptin seems to be involved in reproduction by stimulating gonadotropin-releasing hormone from the hypothalamus.
The body's fat cells, under normal conditions, are responsible for the constant production and release of leptin. This can also be produced by the placenta. Leptin levels rise during pregnancy and fall after parturition (childbirth). Leptin is also expressed in fetal membranes and the uterine tissue. Uterine contractions are inhibited by leptin.
Leptin plays a role in hyperemesis gravidarum (severe morning sickness of pregnancy), in polycystic ovary syndrome and hypothalamic leptin is implicated in bone growth. It has been shown that high levels of Leptin, as usually observed in obese females, can trigger neuroendocrine cascade resulting in early menarche. This may eventually lead to shorter stature as oestrogen secretion starts during menarche and causes early closure of epiphyses.
Effects on bone
Leptin's ability to regulate bone mass was first recognized in 2000. Leptin can affect bone metabolism via direct signalling from the brain, and although leptin acts to reduce cancellous bone, it conversely increases cortical bone. A number of theories have been put forward concerning the cortical-cancellous dichotomy, including a recent theory suggesting increased leptin during obesity may represent a mechanism for enlarging bone size and thus bone resistance to cope with increased body weight.
Bone metabolism is under direct control of the brain, so nerve fibres are present in bone tissue. A number of brain-signalling molecules (neuropeptides and neurotransmitters) have been found in bone, including adrenaline, noradrenaline, serotonin, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y. This evidence supports a direct signalling system between the brain and bone with accumulating evidence suggesting that these molecules are directly involved in the regulation of bone metabolism. Leptin, once released from fat tissue, can cross the blood–brain barrier and bind to its receptors in the brain, where it acts through the sympathetic nervous system to regulate bone metabolism. In addition to its effects through the brain, leptin may act directly on cells in the bone to regulate bone metabolism. In reality, leptin probably signals to bone on multiple levels, with local and systemic checks and balances impacting the final outcome. As a result, the clinical utility of leptin for treatment of bone diseases remains open, but ongoing research may yet provide much-needed therapies for stimulating bone formation.
Leptin receptors are expressed not only in the hypothalamus but also in other brain regions, particularly in the hippocampus. Deficiency of leptin has been shown to alter brain proteins and neuronal functions of obese mice which can be restored by leptin injection. In humans, low circulating plasma leptin has been associated with cognitive changes associated with anorexia, depression, HIV and the development of Alzheimer's disease. Studies in transgenic mouse models of Alzheimer's disease have shown that chronic administration of leptin can ameliorate brain pathology and improve cognitive performance. At the cellular level, the mechanism of leptin action involves reducing b-amyloid and hyperphosphorylated Tau, two hallmarks of Alzheimer's pathology.
Leptin has traditionally been regarded as a link between present fat storage, food intake, and energy expenditure. Leptin playing a role in the long term regulation of energy balance. This link originally arose from animal research findings, but its application to describing human systems has since been challenged. In humans, many instances are seen where Leptin dissociates from the strict role of communicating nutritional status between body and brain and no longer correlates with body fat levels:
- Leptin level is decreased after short-term fasting (24–72 hours), even when changes in fat mass are not observed.
- In obese patients with obstructive sleep apnea, leptin level is increased, but decreased after the administration of continuous positive airway pressure. In non-obese individuals, however, restful sleep (i.e., 8–12 hours of unbroken sleep) can increase leptin to normal levels.
- Serum level of leptin is reduced by sleep deprivation. However, a recent study showed that sleep deprivation was linked with higher levels of leptin.
- Leptin level is increased by perceived emotional stress.
- Leptin level is decreased or increased by increases in testosterone or estrogen level, respectively.
- Leptin level is chronically reduced by physical exercise training.
- Leptin level is increased by dexamethasone.
- Leptin level is increased by insulin.
Factors that acutely affect leptin levels are also factors that influence other markers of inflammation, e.g., testosterone, sleep, emotional stress, caloric restriction, and body fat levels. While it is well-established that leptin is involved in the regulation of the inflammatory response, it has been further theorized that leptin's role as an inflammatory marker is to respond specifically to adipose-derived inflammatory cytokines.
In terms of both structure and function, leptin resembles IL-6 and is a member of the cytokine superfamily. Circulating leptin seems to affect the HPA axis, suggesting a role for leptin in stress response. Elevated leptin concentrations are associated with elevated white blood cell counts in both men and women.
Similar to what is observed in chronic inflammation, chronically elevated leptin levels are associated with obesity, overeating, and inflammation-related diseases, including hypertension, metabolic syndrome, and cardiovascular disease. However, while leptin is associated with body fat mass, the size of individual fat cells, and the act of overeating, it is interesting that it is not affected by exercise (for comparison, IL-6 is released in response to muscular contractions). Thus, it is speculated that leptin responds specifically to adipose-derived inflammation. Leptin is a pro-angiogenic, pro-inflammatory and mitogenic factor, the actions of which are reinforced through crosstalk with IL-1 family cytokines in cancer.
Taken as such, increases in leptin levels (in response to caloric intake) function as an acute pro-inflammatory response mechanism to prevent excessive cellular stress induced by overeating. When high caloric intake overtaxes fat cells' ability to grow larger or increase in number in step with caloric intake, the ensuing stress response leads to inflammation at the cellular level and ectopic fat storage, i.e., the unhealthy storage of body fat within internal organs, arteries, and/or muscle. The insulin increase in response to the caloric load provokes a dose-dependent rise in leptin, an effect potentiated by high cortisol levels. (This insulin-leptin relationship is notably similar to insulin's effect on the increase of IL-6 gene expression and secretion from preadipocytes in a time- and dose-dependent manner.) Furthermore, plasma leptin concentrations have been observed to gradually increase when acipimox is administered to prevent lipolysis, concurrent hypocaloric dieting and weight loss notwithstanding. Such findings appear to demonstrate high caloric loads in excess of fat cells' storage rate capacities lead to stress responses that induce an increase in leptin, which then operates as an adipose-derived inflammation stopgap signaling for the cessation of food intake so as to prevent adipose-derived inflammation from reaching elevated levels. This response may then protect against the harmful process of ectopic fat storage, which perhaps explains the connection between chronically elevated leptin levels and ectopic fat storage in obese individuals.
Recessive mutations in the leptin gene are associated with massive obesity in mice and some humans. Nevertheless no leptin gene mutations have been detected in the majority of obese humans. Treatment with recombinant leptin reduces food intake and body weight. The low leptin levels in patients with leptin mutations are also associated with multiple abnormalities including infertility, diabetes and immune abnormalities all of which are corrected by leptin treatment.
Obesity and leptin resistance
Although leptin reduces appetite as a circulating signal, obese individuals generally exhibit an unusually high circulating concentration of leptin. These people are said to be resistant to the effects of leptin, in much the same way that people with type 2 diabetes are resistant to the effects of insulin. The sustained high concentrations of leptin from the enlarged adipose stores implies leptin desensitization. The pathway of leptin control in obese people might be flawed at some point, so the body does not adequately receive the satiety feeling subsequent to eating.
The main target of leptin action is the leptin receptor that is located in the hypothalamus. In order for circulating leptin to reach its receptor in the hypothalamus, it must first cross the blood-brain barrier. Studies on leptin CSF levels in humans have provided untowardly evidence for leptin obesity-relevant targets being located in brain structures such as the hypothalamus, but the subject remains controversial. For example, in humans leptin in the CSF correlates with BMI but the ratio of CSF to serum leptin decreased with increasing BMI. Also the efficiency of leptin uptake(measured as the CSF:plasma leptin ratio) was lower in human subjects in the highest as compared with the lowest plasma leptin quintile (5.4-fold difference).
Although showing a sluggish leptin-transfer function from plasma to CSF, obese subjects with very high plasma leptin values (300% higher than normal) have 30% more leptin in the CSF than lean individuals, but such abnornally high leptin concentrations in CSF have not prevented their obesity. Since the amount and quality of leptin receptors in hypothalamus of obese humans appear normal (as judged from leptin-mRNA studies), it is inevitable to conclude that leptin resistance in obese individuals is likely to be due to a post leptin-receptor defect, similar to the case of type 2 diabetes, where insulin resistance is due to a post-insulin receptor defect.
Some researchers attempted to explain the failure of leptin to prevent obesity in modern humans as a metabolic disorder, possibly caused by a specific nutrient or a combination of nutrients not present or uncommon in the prehistoric diet. Some proposed "villain" nutrients include lectins and fructose.
A signal-to-noise ratio theory has been proposed to explain the phenomenon of leptin resistance. In healthy individuals, baseline leptin levels are between 1 and 5 ng/dl in men and 7 and 13 ng/dl in women. A large intake of calories triggers a leptin response that reduces hunger, thereby preventing an overload of the inflammatory response induced by caloric intake. In obese individuals, the leptin response to caloric intake is theorized to be blunted due to chronic, low-grade hyperleptinemia, depressing the signal-to-noise ratio such that acute leptin responses have less of a physiological effect on the body.
Although leptin resistance is sometimes described as a metabolic disorder that contributes to obesity, similar to the way insulin resistance is sometimes described as a metabolic disorder that has the potential to progress into type 2 diabetes, it is not certain that it is true in most cases. The mere fact that leptin resistance is extremely common in obese individuals suggests it may simply be an adaptation to excess body weight. The major physiological role of leptin is suggested to be not as a “satiety signal” to prevent obesity in times of energy excess, but as a “starvation signal” to maintain adequate fat stores for survival during times of energy deficit, and leptin resistance in overweight individuals is the standard feature of mammalian physiology, which possibly confers a survival advantage.
A different form of leptin resistance (in combination with insulin resistance and weight gain) easily arises in laboratory animals (such as rats), as soon as they are given unlimited (ad libitum) access to palatable, energy-dense foods, and it is reversed when these animals are put back on low energy-density chow. That, too, may have an evolutionary advantage: "the ability to efficiently store energy during periods of sporadic feast represented a survival advantage in ancestral societies subjected to periods of starvation." The combination of two mechanisms (one, which temporarily suspends leptin action when presented with excess of high-quality food, and the other, which blunts the processes that could drive the body weight back to "normal"), could explain the current obesity epidemic without invoking any metabolic disorders or "villain" nutrients.
Although the notion of obesity as a state of 'leptin resistance' has become ingrained in the minds of many researchers, some observations do not directly support this contention. For example, the work of Rudolph Leibel at Columbia University has shown that, in both obese and lean individuals, leptin injections do not reduce body mass. Despite the lack of response in obese and lean subjects, there is little argument that lean subjects are also leptin-resistant; hence, whether obese subjects are in fact resistant to leptin remains to be empirically demonstrated. This finding also underscores the notion that the brain is not designed to respond to increased leptin by decreasing food intake; rather, as discussed above, lack of leptin acts as a signal to increase food intake. Indeed, Leibel's work has shown that the decreases in serum leptin that occur post-weight-loss constitute a state of leptin deficiency, which drives increased appetite. As such, leptin injections in weight-reduced patients can prevent the increases in appetite and thereby allow patients to maintain weight loss. These studies therefore demonstrate that leptin treatment may be a useful strategy to treat obesity in humans, if not by driving weight loss directly then by allowing weight loss (as a result of diet and exercise) to be more readily maintained.
Interactions with fructose
The consumption of high amounts of fructose is suggested to cause leptin resistance and elevated triglycerides in rats. The rats consuming the high-fructose diet subsequently ate more and gained more weight than controls when fed a high-fat, high-calorie diet. These studies, however, did not control against other monosaccharides or polysaccharides, therefore leptin resistance may be a result of a diet that contains high saccharide indices (soda, candy, and other foods with easily liberated sugar).
Leptin and weight regain
Dieters who lose weight experience a drop in levels of circulating leptin. This drop causes reversible decreases in thyroid activity, sympathetic tone, and energy expenditure in skeletal muscle, and increases in muscle efficiency and parasympathetic tone. The result is that a person who has lost weight has a lower basal metabolic rate than an individual at the same weight who has never lost weight; these changes are leptin-mediated, homeostatic responses meant to reduce energy expenditure and promote weight regain. Many of these changes are reversed by peripheral administration of recombinant leptin to restore pre-diet levels.
A decline in levels of circulating leptin also changes brain activity in areas involved in the regulatory, emotional, and cognitive control of food intake that are reversed by administration of leptin.
Mechanism of action
Leptin interacts with six types of receptors (Ob-Ra–Ob-Rf, or LepRa-LepRf), that in turn are encoded by a single gene, LEPR. Ob-Rb is the only receptor isoform that can signal intracellularly via the Jak-Stat and MAPK signal transduction pathways, and is present in hypothalamic nuclei.
Whether leptin can cross the blood–brain barrier to access receptor neurons is unknown, because the blood–brain barrier is attenuated in the area of the median eminence, close to where the NPY neurons of the arcuate nucleus are located. Leptin is generally thought to enter the brain at the choroid plexus, where the intense expression of a form of leptin receptor molecule could act as a transport mechanism.
Once leptin has bound to the Ob-Rb receptor, it activates the stat3, which is phosphorylated and travels to the nucleus to presumably effect changes in gene expression. One of the main effects on gene expression is the down-regulation of the expression of endocannabinoids, responsible for increasing appetite. Other intracellular pathways are activated by leptin, but less is known about how they function in this system. In response to leptin, receptor neurons have been shown to remodel themselves, changing the number and types of synapses that fire onto them.
Leptin action is recognized to be more decentralized than previously assumed. In addition to its endocrine action at a distance (from adipose tissue to brain), leptin also acts as a paracrine mediator.
Recently, leptin microinjections into the nucleus of the solitary tract (NTS) have been shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular responses to activation of the chemoreflex.
An analog of human leptin, metreleptin, has been approved in Japan for metabolic disorders including lipodystrophy and in the United States as replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy. Metreleptin is currently being investigated for the treatment of diabetes and/or hypertriglyceridemia, in patients with rare forms of lipodystrophy, syndromes characterized by abnormalities in adipose tissue distribution, and severe metabolic abnormalities.
Affects one in three adults
Affecting about 35 percent of all adults in the United States according to the CDC, metabolic syndrome contributes to weight gain, by causing a state of internal starvation called metabolic starvation. This in turn leads to increases hunger, sugar cravings and increased portions leading to overeating and weight gain.
Cause and effect misunderstood
Since we traditionally thought that the portion control (which in turn was attributed wrongly to poor will power)is the cause of weight gain, rather than the effect of this metabolic starvation, all our traditional ideas about cause and effect of obesity were not only wrong but lead to the “blame the victim” attitude when it comes to obesity.
Secret of weight gain revealed
Secret of weight gain, and metabolic syndrome revealed - it has been recently proven that metabolic syndrome, and the weight gain itself are caused by a process called insulin resistance. Check your metabolic syndrome risk using the free Metabolic syndrome meter. Watch this amazing Ted Med video that reveals the secret of weight loss - Stop blaming the victim for obesity
- Leptin in a bulletin by the Howard Hughes Medical Institute (HHMI)
- Leptin: Your brain, appetite and obesity by the British Society of Neuroendocrinology
- Leptin/ghrelin and their role in obesity from hungerhormones.com, a weight control website
- Leptin by Colorado State University
- Leptin at 3Dchem.com, description and structure diagrams
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