Leptin (from the Greek ?????? leptos , "skinny"), "energy-releasing hormone", is a hormone made predominantly by adipose cells that help to regulate energy balance by inhibiting hunger. Leptin is opposed by the action of the hormone ghrelin, "hormone hunger". Both hormones act on the receptors in the arcuate nucleus of the hypothalamus. In obesity, a decrease in susceptibility to leptin occurs (similar to insulin resistance in type 2 diabetes), resulting in an inability to detect satiety despite high energy stores and high leptin levels.
Although the regulation of fat storage is considered a major function of leptin, it also plays a role in other physiological processes, as evidenced by many synthesis sites other than fat cells, and many types of cells in addition to leptin-hypothalamus receptor cells. Many of these additional functions still have to be defined.
Video Leptin
Identifikasi gen encoding
In 1949, the non-obese colonies studied at the Jackson Laboratory produced a strain of obese offspring, suggesting that mutations have occurred in hormones that govern starvation and energy expenditure. Homozygous mice for so-called ob mutation (ob/ob) ate greedily and massively obese. In the 1960s, the second mutation that led to obesity and similar phenotypes was identified by Douglas Coleman, also at the Jackson Laboratory, and was given the name diabetes (db), as both ob/ob and db/db were obese. In 1990, Rudolph Leibel and Jeffrey M. Friedman reported gene mapping db .
Consistent with the Coleman and Leibel hypothesis, some subsequent research from the Leibel and Friedman labs and other groups confirmed that the ob gene encodes new hormones circulating in the blood and that can suppress food intake and weight in obese and wild mice, but not db mice.
In 1994, Friedman's laboratory reported gene identification. In 1995, Jose F. Caro's laboratory provided evidence that mutations in mouse genes do not occur in humans. Furthermore, since the expression of the ob gene increases, not decreases, in human obesity, it suggests resistance to leptin is a possibility. At Roger Guillemin's suggestion, Friedman named this new hormone "leptin" from Greek lepto which means thin. Leptin is the first derived fat cell hormone (adipokine) to be found.
Subsequent studies in 1995 confirmed that the db gene encodes the leptin receptor, and it is expressed in the hypothalamus, a region of the brain known to regulate the sensation of hunger and weight.
Maps Leptin
Recognition of scientific progress
Coleman and Friedman have been awarded many prizes that recognize their role in leptin discovery, including the Gairdner Foundation International Award (2005), Shaw Prize (2009), Lasker Award, BBVA Foundation Knowledge Leadership Foundation and International Faisal King Prize, Leibel has not received a recognition level similar to the discovery because he was omitted as one of the authors of a scientific paper published by Friedman who reported the discovery of the gene. The various theories surrounding Leibel's omission from Friedman and others as co-authors of this paper have been presented in numerous publications, including Ellen Ruppel Shell's 2002 book The Hungry Gene.
The discovery of leptin is also documented in a series of books including the Fat: Fighting the Obesity Epidemic by Robert Pool, The Hungry Gene by Ellen Ruppel Shell, and Thin Rethinking: New Science of Decrease Weight Loss and Myths and Reality from Dieting by Gina Kolata. Fat: Fighting the Obesity Epidemic and Thinking Back Thin: New Science on Weight Loss and Myths and Reality Diet reviews work in Friedman labs that lead to ob gene cloning, while The < i> Hungry Gene drew attention to Leibel's contribution.
Gene location and hormone structure
Gen Ob (Lep) (Ob for obesity, Lep for leptin) lies in chromosome 7 in humans. Human leptin is 16-kDa protein from 167 amino acids.
Mutations
A human mutant leptin was first described in 1997, and then six additional mutations were described. All affected are from Eastern countries; and all have leptin variants that are undetectable by standard immunoreactive techniques, so low or undetectable leptin levels. The recently-described eighth mutation reported in January 2015, in a child with Turkish parents, is unique in that it is detected by standard immunoreactive techniques, in which leptin levels increase; but leptin does not activate leptin receptors, then patients have functional leptin deficiency. These eight mutations all cause extreme obesity in infancy, with hyperphagia.
Nonsense
Nonsense mutations in the leptin gene resulting in stop codon and lack of leptin production were first observed in mice in 1950. In mouse genes, arginine-105 was encoded by CGA and required only one nucleotide change to create a TGA stop codon. Suitable amino acids in humans are encoded by a CGG sequence and will require two nucleotides to be altered to produce stop codons, which are much less likely to occur.
Frameshift
A recessive frameshift mutation resulting in leptin reduction has been observed in two children who have confidence in adolescent obesity.
Polymorphism
The Human Genome Equivalent (HuGE) review in 2004 looked at research on the relationship between genetic mutations that affect leptin regulation and obesity. They reviewed common polymorphisms in the leptin gene (A19G, frequency 0.46), three mutations in the leptin receptor gene (Q223R, K109R and K656N) and two mutations in the PPARG gene (P12A and C161T). They found no association between any of the polymorphisms and obesity.
A 2006 study found an association between LEP-2548 G/A genotypes and morbid obesity in native Taiwans, but meta-analysis in 2014 was not, however, this polymorphism has been associated with weight gain in patients taking antipsychotics.
LEP-2548 G/A polymorphism has been associated with an increased risk of prostate cancer, gestational diabetes, and osteoporosis.
Other rare polymorphisms have been found but their association with obesity is inconsistent.
Transversion
One case of homozygous transversive mutations from gene encoding for leptin was reported in January 2015. This led to functional leptin deficiency with high levels of leptin in the circulation. Transversion of (c.298G -> T) converts aspartic acid into tyrosine at position 100 (p.D100Y). Leptin mutants can not bind or activate leptin receptor in vitro , or in leptin defects in vivo . Found in two-year-old boys with extreme obesity with recurrent ear and pulmonary infections. Treatment with metreleptin leads to "rapid changes in feeding behavior, reduced daily energy intake, and considerable weight loss".
Synthesis site
Leptin is produced primarily in adipocytes of white adipose tissue. It is also produced by brown adipose tissue, placenta (syncytiotrophoblasts), ovaries, skeletal muscles, stomach (lower part of the funda gland), mammae epithelial cells, bone marrow, gastric head cells and P/D1 cells.
Blood level
Leptin circulates in the blood in free form and is bound to proteins.
Physiological variations
Leptin levels vary exponentially, not linearly, with fat mass. Leptin levels in the blood are higher between midnight and morning, possibly suppressing appetite at night. Diurnal rhythm of blood leptin level can be modified by meal time.
Under certain conditions
In humans, many examples are seen in which leptin dissociates from the rigorous role of communicating nutritional status between body and brain and is no longer correlated with body fat levels:
- Leptin levels increase due to emotional distress.
- Leptin levels are reduced chronically with physical exercise.
- Leptin levels decrease due to increased testosterone levels and increase due to increased estrogen levels.
- Leptin levels are increased by insulin.
- The release of leptin is enhanced by dexamethasone.
- In obese patients with obstructive sleep apnea, leptin levels increase, but decrease after continuous positive air pressure. However, in non obese individuals, restful sleep (ie, 8-12 hours of unbroken sleep) may increase leptin to normal levels.
Leptin mutant
All known leptin mutations except those associated with low immunoreactive leptin levels are undetectable. The exception is mutant leptin reported in January 2015 that is not working, but is detected by standard immunoreactive methods. It is found in massively overweight 2-1/2 year old boys who have high circulating leptin levels that have no effect on leptin receptors, so he is functionally leptin-deficient.
Effects
For the most part, leptin "energy-releasing hormone" is made by adipose cells, so it is labeled specific fat cells . In the context of its influence, it is important to recognize that short words explaining directly , middle , and primer are not used interchangeably. With regard to the hormone leptin, central vs. peripheral refers to the hypothalamus part of the brain vs the non-hypothalamus leptin action location; direct vs indirectly refers to whether there is no intermediary, or there is an intermediary in leptin action mode; and primary vs. secondary are random descriptions of a particular leptin function.
Central nervous system
In vertebrates, the nervous system consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The main effect of leptin is in the hypothalamus, part of the central nervous system. Leptin receptors are expressed not only in the hypothalamus but also in other brain regions, especially in the hippocampus. Thus some leptin receptors in the brain are classified as central (hypothalamus) and some as peripheral (non-hypothalamus).
As far as is known scientifically, the general effects of leptin in the central nervous system are:
- Leptin deficiency has been shown to alter brain proteins and neuronal function in obese mice that can be recovered by leptin injection.
- In humans, low circulating leptin plasma has been associated with cognitive changes associated with anorexia, depression, and Alzheimer Disease. The study on transgenic mouse models of Alzheimer's disease has shown that chronic leptin administration can improve brain pathology and improve cognitive performance, by reducing b-amyloid and hyperphosphorylated Tau, two hallmarks of Alzheimer's pathology.
Generally, leptin is thought to enter the brain in the choroid plexus, where the intense expression of the leptin receptor molecular form can act as a transport mechanism.
Increased melatonin levels lead to a decrease in leptin regulation; however, melatonin also appears to increase leptin levels in the presence of insulin, leading to decreased appetite during sleep. Partial sleep deprivation is also associated with a decrease in leptin levels.
Mice with type 1 diabetes treated with leptin or leptin plus insulin, compared with insulin alone have a better metabolic profile: blood sugar does not fluctuate so much; decreased cholesterol levels; less body fat is formed.
Hypothalamus
Leptin acts on the receptor in the lateral hypothalamus to inhibit the hunger and the medial hypothalamus to stimulate satiety.
- In the lateral hypothalamus, leptin inhibits hunger
- counteract the effects of Y neuropeptide, a powerful hunger promoter secreted by cells in the intestine and in the hypothalamus
- counteracts the effects of anandamide, another powerful hunger promoter that binds to the same receptor as THC
- In the medial hypothalamus, leptin stimulates satiety
- promote synthesis? -MSH, hunger suppressant
Thus, lesions in the lateral hypothalamus cause anorexia (due to lack of hunger signals) and lesions in the medial hypothalamus causing excessive hunger (due to lack of a full signal). This inhibition of appetite is long term, in contrast to the rapid inhibition of hunger by cholecystokinin (CCK) and a slower emphasis of starvation between foods mediated by PYY3-36. The absence of leptin (or its receptors) causes uncontrolled hunger and leads to obesity. Fasting or following a very low-calorie diet lowers leptin levels. Leptin levels change more when food intake decreases than when it increases. The dynamics of leptin because of acute changes in the energy balance may be related to appetite and finally, for food intake rather than fat stores.
- It controls food intake and energy expenditure by acting on a receptor in the mediobasal hypothalamus.
Leptin binds neuropeptide Y (NPY) neurons in the arcuate nucleus in such a way as to reduce the activity of these neurons. Leptin signals the hypothalamus that produces satiety. What's more, the leptin signal can make it easier for people to resist the temptation of high-calorie foods.
Activation of leptin receptors inhibits neuropeptide Y and agouti-related peptide (AgRP), and activates? -melanocyte-stimulating hormone (? -MSH). NPY neurons are a key element in starvation regulation; Small doses of NPY injected into the brains of experimental animals stimulate feeding, while the selective destruction of NPY neurons in mice causes them to become anorexic. On the contrary? -MSH is an important mediator of satiety, and the gene difference for the -MSH receptor associated with obesity in humans.
Leptin interacts with six types of receptors (Ob-Ra-Ob-Rf, or LepRa-LepRf), which in turn are encoded by a single gene, LEPR. Ob-Rb is the only receptor isoform capable of intracellular signaling through the signal transduction pathway of Jak-Stat and MAPK, and is present in the hypothalamus nucleus.
Once leptin is bound to the Ob-Rb receptor, it activates stat3, which is phosphorylated and moves to the nucleus to influence the change in gene expression, one of the main effects is the down-regulation of endocannabinoid expression, responsible for increasing hunger. In response to leptin, receptor neurons have been shown to remodel themselves, altering the number and type of synapses that are firing on them.
Circulation system
The role of leptin/leptin receptors in the modulation of T cell activity in the immune system is demonstrated in trials with mice. It modulates the immune response to atherosclerosis, in which obesity is a predisposing factor.
Exogenous leptin may increase angiogenesis by increasing levels of vascular endothelial growth factor.
Hyperleptinemia produced by intravenous or adenoviral gene transfer lowers blood pressure in mice.
Leptin microinection into the nucleus of the solitary canal (NTS) has been shown to induce sympathetic responses, and potentiates cardiovascular responses to chemoreflex activation.
Fetal lung
In the fetal lungs, leptin is induced in interstitial alveolar fibroblasts ("lipofibroblasts") by PTHRP action secreted by formative alveolar epithelium (endoderm) under moderate stretching. Leptin from mesenchyme, in turn, reacts to the epithelium at leptin receptors carried in alveolar type II pneumocytes and induces surfactant expression, which is one of the main functions of type II pneumonia.
Reproductive System
Ovulation Cycle
In mice, and to a lesser extent in humans, leptin is necessary for male and female fertility. The ovulation cycle in women is related to the energy balance (positive or negative depending on whether a woman loses or gains weight) and the energy flux (how much energy is consumed and excreted) is more than the energy status (fat level). When the energy balance is very negative (which means the woman is starving) or the energy flux is very high (meaning the woman is exercising at an extreme level, but still consumes enough calories), the ovarian cycle stops and the woman stops menstruating. Only if a woman has a very low body fat percentage, energy status affects menstruation. Leptin levels beyond the ideal range may have a negative effect on the quality and yield of eggs during in vitro fertilization . Leptin is involved in reproduction by stimulating the hormone releasing gonadotropins from the hypothalamus.
Pregnancy
The placenta produces leptin. Leptin levels increase during pregnancy and fall after delivery. Leptin is also expressed in the fetal membrane and 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 involved in bone growth in mice.
Lactation
Immunoreactive leptin has been found in human breast milk; and leptin from breast milk has been found in the blood of baby animals that suckle.
Publish
Leptin along with kisspeptin controls the onset of puberty. High levels of leptin, as commonly observed in obese women, can trigger a neuroendocrine cascade that results in early menarche. This can ultimately lead to a shorter stature as estrogen secretion begins during menarche and causes early closure of the epiphyses.
Bone
Lepin's ability to regulate bone mass was first recognized in 2000. Leptin can affect bone metabolism through direct signals from the brain. Leptin decreases cancellous bone, but increases cortical bone. This "cortical-cancellous dichotomy" may represent a mechanism to enlarge bone size, and thus bone resistance, to overcome weight gain.
Bone metabolism can be regulated by central sympathetic flow, because the sympathetic pathways supply the bone tissue. A number of brain signaling molecules (neuropeptides and neurotransmitters) have been found in bone, including adrenaline, noradrenaline, serotonin, calcitonin-related peptide genes, vasoactive intestinal peptides and Y neuropeptides. Leptin binds to its receptor in the hypothalamus, where it acts. through the sympathetic nervous system to regulate bone metabolism. Leptin can also act directly on bone metabolism through a balance between energy intake and IGF-I pathways. There is potential for the treatment of bone forming diseases - such as impaired fracture healing - with leptin.
Immune system
Factors that acutely affect leptin levels are also factors that influence other inflammatory markers, for example, testosterone, sleep, emotional stress, calorie restriction, and body fat levels. While it is well established that leptin is involved in regulating inflammatory responses, it has been suggested that the role of leptin as an inflammatory marker is to respond specifically to the adipose-derived inflammatory cytokines.
In terms of structure and function, leptin resembles IL-6 and is a member of the cytokine superfamily. Circulating leptin appears to affect the HPA axis, indicating the role of leptin in the stress response. Increased concentrations of leptin are associated with an increase in the number of white blood cells in men and women.
Similar to what is observed in chronic inflammation, elevated levels of chronic leptin are associated with obesity, overeating, and inflammatory diseases, including hypertension, metabolic syndrome, and cardiovascular disease. Although leptin is associated with body fat mass, however, the size of individual fat cells, and overeating, is interesting that it is unaffected by exercise (for comparison, IL-6 is released in response to muscle contraction). Thus, it is speculated that leptin responds specifically to inflammation derived from adipose. Leptin is a pro-angiogenic, pro-inflammatory and mitogenic factor, a reinforced action through crosstalk with IL-1 family cytokines in cancer.
Taken as such, elevated leptin levels (in response to caloric intake) serve as an acute pro-inflammatory response mechanism to prevent excessive cellular stress caused by overeating. When high calorie intake weighs the ability of fat cells to grow larger or increase in amounts in steps with calorie intake, subsequent stress responses lead to inflammation at the cellular level and storage of ectopic fat, which is the storage of unhealthy body fat in the organs internal. , arteries, and/or muscles. Increased insulin in response to caloric loads provokes dose increases depending on leptin, an effect reinforced by high levels of cortisol. (This insulin-leptin relationship is particularly similar to the effect of insulin on increasing the expression of IL-6 gene and the secretion of preadipocytes in time and dose dependent.) Furthermore, plasma leptin concentration has been observed gradually increased when acipimox is administered to prevent lipolysis, concurrent hypocaloric diets and weight loss though. These findings appear to show a high calorie load exceeding the storage capacity capacity of fat cells causing a stress response that leads to increased leptin, which then operates as circulation-derived adipose stop-stopping for cessation of food intake thus preventing adipose. inflammation-resulted from reaching a high level. This response can then protect against the dangerous process of ectopic fat storage, which may explain the relationship between chronically elevated leptin levels and ectopic fat storage in obese individuals.
Role in obesity and weight loss
Obesity
Although leptin reduces appetite as a circulating signal, obese individuals generally exhibit higher leptin concentrations than individuals with normal weight due to higher body fat percentage. These people show resistance to leptin, similar to insulin resistance in type 2 diabetes, with increased levels of failure to control hunger and modulate their weight. A number of explanations have been put forward to explain this. An important contributor to leptin resistance is a change in leptin receptor signaling, especially in the arcuate nucleus; however, deficiencies, or major changes in leptin receptors themselves are not considered a major cause. Other suggested explanations include changes in the way leptin crosses blood brain barrier (BBB) ​​â € Studies at the level of leptin cerebrospinal fluid (CSF) provide evidence for leptin reduction across the BBB and achieve relevant obesity targets, such as the hypothalamus, in obese people. In humans it has been observed that the ratio of leptin in CSF compared with blood is lower in obese than in people of normal weight. The reason for this may be the high triglyceride levels that affect the transport of leptin throughout the BBB or because the leptin transporter becomes saturated. Although the deficit in leptin transfer from plasma to CSF ​​is seen in obese people, they are still found to have 30% more leptin in their CSF than skinny people. This higher CSF level fails to prevent their obesity. Since the amount and quality of leptin receptors in the hypothalamus seems normal in most obese individuals (as assessed by leptin-mRNA studies), the leptin likelihood in these individuals is due to post-insulin receptor deficits seen in diabetes type 2. When leptin binds to leptin receptors, it activates a number of pathways. Leptin resistance may be caused by defects in one or more parts of this process, especially the JAK/STAT pathway. Mice with mutations in the leptin receptor gene that prevent STAT3 activation are obese and show hyperphagia. The PI3K pathway may also be involved in leptin resistance, as has been demonstrated in rats with artificial blocking of PI3K signaling. The PI3K pathway is also activated by insulin receptors and is therefore an important area in which leptin and insulin act together as part of the energy homeostasis. The insulin-pI3K pathway may cause the POMC neuron to become insensitive to leptin via hyperpolarization. Consumption of a high fructose diet from birth was associated with decreased leptin levels and reduced expression of leptin receptor mRNA in mice. Long-term fructose consumption in rats has been shown to increase triglyceride levels and trigger leptin and insulin resistance, however, other studies have found that leptin resistance only develops in the presence of both high fructose and high fat levels in foods. A third study found that high fructose levels reversed leptin resistance in mice fed a high-fat diet. The contradictory results mean that it is uncertain whether leptin resistance is caused by high levels of carbohydrates or fats, or if an increase in both is required. Leptin is known to interact with amylin, a hormone involved in emptying the stomach and creating a feeling of satiety. When both leptin and amylin are administered to obese leptin, a sustained weight loss is seen. Because of its apparent ability to reverse leptin resistance, amylin has been suggested as a possible therapy for obesity. It has been suggested that the main role of leptin is to act as a signal of hunger when it is low, to help maintain fat stores for survival during times of famine, rather than satiety signals to prevent overeating. Leptin levels signal when an animal has enough stored energy to spend in a search other than getting food. This means that leptin resistance in obese people is a normal part of mammalian physiology and may, may provide survival benefits. Leptin resistance (in combination with insulin resistance and weight gain) was seen in mice after they were given unrestricted access to a delicious solid food meal. This effect is reversed when animals are returned to a low-energy diet. It may also have an evolutionary advantage: enabling energy to be stored efficiently when food is plentiful would be advantageous in populations where food is often scarce. Response to weight loss
Weight loss dieters, especially those with overflowing fat cells, decreased circulating leptin levels. This decrease causes a reversible decrease in thyroid activity, sympathetic tone, and energy expenditure in skeletal muscle, and increased muscle efficiency and parasympathetic tone. The result is that a person who has lost weight has a lower basal metabolic rate than an individual with the same weight as that weight without previous weight loss; this change is a leptin-mediated homeostatic response intended to reduce energy expenditure and increase weight again as a result of fat cells that shrink below normal size. Many of these changes are reversed by peripheral administration (intravenously into the arm, arm, leg, or leg veins) of recombinant leptin to restore pre-dietary levels.
A decrease in circulating leptin levels also alters brain activity in the areas involved in the regulation, emotional, and cognitive control of the appetite inversely associated with leptin administration.
Role in shared issues and obesity
Obesity and osteoarthritis
Osteoarthritis and obesity are closely related. Obesity is one of the most important factors that can be prevented for the development of osteoarthritis.
Initially, the relationship between osteoarthritis and obesity is considered exclusively based on biomechanics, which he says is overweight, causing joints to wear out faster. However, today we recognize that there are also metabolic components that explain why obesity is a risk factor for osteoarthritis, not only for weight-bearing joints (eg, knees), but also for joints that do not bear weight (eg, hands). As a result, it has been proven that decreasing body fat reduces osteoarthritis to a greater extent than weight loss per se. This metabolic component is associated with the release of systemic factors, the nature of pro-inflammatory, by adipose tissue, which is often critically associated with the development of osteoarthritis.
Thus, the production of adipokine and regulated inflammatory mediators, hyperlipidemia, and increased systemic oxidative stress are conditions often associated with obesity that can support joint degeneration. In addition, many regulatory factors have been implicated in the development, maintenance and function, both adipose tissue, as well as cartilage and other joint tissues. Changes in these factors can be an additional link between obesity and osteoarthritis.
Leptin and osteoarthritis
Adipocytes interact with other cells through the production and secrete a variety of signal molecules, including cell signal proteins known as adipokines. Certain adipokines may be considered hormones, because they regulate organ function in the distance, and some of them are specifically involved in the physiopathology of joint disease. In particular, there is one, leptin, which has been the focus of attention for research in recent years.
Levels of circulating leptin positively correlate with Body Mass Index (BMI), more specifically with fat mass, and obese individuals have higher leptin levels in their blood circulation, compared with non-obese individuals. In obese individuals, elevated circulating leptin levels induce unwanted responses, that is, reducing food intake or losing weight does not occur because there is resistance to leptin (ref 9). In addition to the function of regulating energy homeostasis, leptin plays a role in other physiological functions such as neuroendocrine communication, reproduction, angiogenesis and bone formation. More recently, leptin has been recognized as a cytokine factor as well as with pleiotropic action also in the immune and inflammatory response. For example, leptin can be found in synovial fluid correlated with body mass index, and leptin receptor is expressed in cartilage, where leptin mediates and modulates many inflammatory responses that can damage cartilage and other joint tissues. Leptin thus appears as a candidate for linking obesity and osteoarthritis and serves as a clear goal as a nutritional treatment for osteoarthritis.
As in plasma, leptin levels in the synovial fluid are positively correlated with BMI. Leptin from the synovial fluid is synthesized at least partially inside the joint and may originate partially in the circulation. Leptin has been shown to be produced by chondrocytes, as well as by other tissues in the joint, including synovial tissue, osteophytes, meniscus and bone. An extra-joint extracellar lipid joint in the knee joint is also adjacent to the synovial membrane and cartilage, and has recently been highly regarded as an important source of leptin, as well as adipokines and other mediators that contribute to the pathogenesis of osteoarthritis.
The risk of suffering from osteoarthritis may decrease with weight loss. This risk reduction is partly related to the decrease in load on the joints, but also on the decrease in fat mass, central adipose tissue and low levels of inflammation associated with obesity and systemic factors.
This growing evidence suggests leptin as a cartilage degradation factor in the pathogenesis of osteoarthritis, and as potential biomarkers in disease progression, suggesting that leptin, as well as regulatory and signaling mechanisms, could be a new and promising target in the treatment of osteoarthritis, especially in obese patients.
Obese individuals tend to develop osteoarthritis, not only because of mechanical overload, but also because of the excessive expression of soluble factors, ie, leptin and pro-inflammatory cytokines, which contribute to joint inflammation and cartilage damage. Thus, obese individuals are in altered conditions, due to metabolic inadequacy, requiring special nutritional treatment capable of normalizing leptin production and reducing systemic low-level inflammation, to reduce the harmful effects of this systematic mediator on joint health.
There are nutritional supplements and pharmacological agents that are able to guide these factors and improve both conditions.
Therapeutic use
Leptin
Leptin is approved in the United States in 2014 for use in congenital leptin deficiency and general lipodystrophy.
Metreleptin analogy
An analogue of leptin metreleptin (Myalept trade name) was first approved in Japan in 2013, and in the United States in February 2014. In the US it is indicated as a treatment for leptin deficiency complications, and for diabetes and associated hypertriglyceridemia. with common or acquired standard lipodystrophy.
See also
- NAPEs
- Leptin Teleost
Note
References
External links
- Leptin: Your brain, appetite, and obesity by the British Society of Neuroendocrinology
- Leptin by Colorado State University - a great illustration, but last updated in 1998
- Leptin in 3Dchem.com, description and structure of the diagram
Source of the article : Wikipedia
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