Leptin is not only a fat cell hormone, it is also a product of the ob gene, which controls obesity, and homozygous mutations in which, provoke its extreme degree. Leptin also circulates in the bloodstream and is considered a signaling form of the receptor responsible for human eating behavior. In addition to leptin, insulin receptors responsible for the development of diabetes are localized in the hypothalamic centers. They are affiliated with the gene for this disease: db/db, which is also activated by hypothalamic neurons.
This is crucial in the regulation of energy balance and glucose homeostasis. Unfortunately, it is now scientifically confirmed that neither leptin treatment nor sensitization to the hormone usually produces positive results in the treatment of obesity. Instead, the role of leptin is likely to be reduced to signaling nutritional deficiencies to form the appropriate neuroendocrine responses. This is what our article is about.
- Production and release of the hormone into the blood.
- Leptin and digestive tube diseases.
- Sensory gut transduction.
Production and release of the hormone into the blood
The leptin gene is localized on the alleles of chromosome 7 and consists of three components – exons (nucleotide sequences of the gene). The matrix RNA of leptin is 3.5 kb in length and encodes a signal peptide and a mature protein. This allows leptin to be powerfully expressed (transferring information from DNA to RNA) in white fat, mammary epithelium and bone marrow.
Fat layers in overweight patients contain about 20 ng/ml leptin, in plasma the hormone is about 100 ng/ml, and with a gene mutation this concentration rises to 700 ng/ml. In this case, leptin production and release are environmentally correlated. Obesity activates the synthesis of the hormone and increases its plasma levels. This has been confirmed by scientific studies that have been conducted on humans.
Exercise minimizes leptin concentrations in the blood, as do low temperatures. But starvation weakens leptin gene expression, while increased nutrition restores it.
Leptin and digestive tube diseases
Leptin is involved in maintaining the integrity of the gastric epithelium, acting as a gastroprotector. This is correlated with an increase in leptin production by the stomach during its experimental damage or as a result of Helicobacter pylori infection. This cytoprotective effect of leptin in the stomach involves activation of blood flow rate against the background of local production of prostaglandin and nitric oxide. Plus – activation of vagus nerve mechanisms.
One of the most important functions of the hormone is considered to be its involvement in controlling the development of inflammatory responses. There is ample evidence for this, confirming a leptin-mediated signaling pathway and the ability to activate innate and adaptive immunity through mutations in target transcription genes. It is clear, however, that the affiliation of leptin with obesity suggests the development of pathological changes in the digestive tube in the background of inflammation.
The mechanism of this development is related to T-cells of the immune system, which control inflammation in the human body. Inflamed cells of the human colon, for example, exhibit strong leptin immunoreactivity, which cumulates in the subapical part of these cells, whereas normal epithelium shows no such predisposition.
This suggests once again that fat and intestinal leptin are key elements in controlling the development of inflammation in the intestine. Whether aberrant leptin expression is a trigger or, conversely, a consequence of developed inflammation in the colonic mucosa or whether the hormone helps to progress and prolong chronic inflammation remains to be clarified by researchers.
In addition to this proinflammatory effect of leptin, hormone signaling may be an important element in protecting the mucosa from infection. Thus, the receptor mutation is correlated with increased susceptibility to Entamoeba histolytica infection with maximal ability to destroy digestive tract mucosa.
Sensory gut transduction
Leptin is an amino acid protein of adipocytes. Its blood levels indicate the body’s total energy reserves, which tend to accumulate in fat depots. The main effect of the hormone is to reduce food intake. In addition, leptin is a member of the cytokine family. There are 5 different receptor isoforms of the substance. Short – transports leptin from the blood through the blood-brain barrier to the hypothalamus.
The long one is localized in the nuclei of hypothalamus, where leptin inactivates kinase. Small amounts of the hormone are synthesized by gastric cells and the placenta, so it is present in breast milk. At the periphery, leptin minimizes food intake, but this effect is minimized when obesity occurs. But when the hormone enters the CNS, already obese patients respond quite normally to the hormone and reduce food intake. This suggests that leptin resistance in obesity develops at the level of the hormone receptor involved in transporting leptin across the blood-brain barrier.
The ability of the hormone to minimize food intake occurs in the brain due to minimization of non-ropeptide activity and by increasing α-melanocyte-stimulating hormone, which blocks food intake. In the periphery, leptin turns on synergy to reduce food intake. Without the hormone receptors in the animal experiment, these properties are lost. However, they can always be restored by genetic restoration of the leptin receptor in the hypothalamus. Losses are possible with leptin resistance.
Blood levels of leptin increase as obesity progresses. Leptin is probably responsible for total energy stores and energy expenditure along with other adipose tissue hormones. At the cellular level, larger adipocytes synthesize more of the hormone, while smaller ones synthesize less. Because of leptin’s effect on food intake, it was initially thought that exogenous leptin could be used therapeutically to treat obesity. However, clinical trials show very little activity in losing extra pounds. There is evidence that deficient blood leptin levels are a trigger for familial obesity, but this is rare.