Description. Leptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. The extreme hunger leads to chronic excessive eating (hyperphagia) and obesity.
Clinical Applications of Leptin in Leptin Deficiency
In addition, leptin treatment in children with congenital leptin deficiency results in normalization of several neuroendocrine axes, including the reproductive and thyroid axes, and of immune function and cognitive development.
Leptin resistance usually develops over time due to three primary factors: (1) too little sleep, (2) too much stress and (3) too much of the wrong foods. Other factors that can contribute to its development include: Overeating. High insulin levels.
In humans, leptin deficiency is observed in lipodystrophy syndromes, which present with low or absent leptin levels due to abnormal deposition and distribution of adipose tissue. In addition, congenital human leptin deficiency may also be caused by mutations in the leptin gene.
Absence of leptin makes the body think it does not have any fat whatsoever and this results in uncontrolled food intake and severe childhood obesity. In addition, leptin deficiency may cause delayed puberty and poor function of the immune system.
Leptin levels decline during weight loss and signal to the hypothalamus to stimulate feeding, reduce energy expenditure, and promote weight regain.
Management and treatment
Congenital leptin deficiency can be successfully treated with daily subcutaneous injections of recombinant human leptin, resulting in sustained positive effects on weight loss, reducing appetite, appropriate pubertal development and hyperinsulinaemia.
Leptin is a 16-kDa peptide hormone produced mainly by adipocytes, although other tissues and organs, such as mammary gland, ovary, skeletal muscle, stomach, pituitary gland and lymphoid tissue may produce lower amounts, possibly for local action.
Scientists Discover a Destructive Mechanism That Blocks the Brain from Knowing When to Stop Eating. Mice fed a high-fat diet produce an enzyme named MMP-2 that clips receptors for the hormone leptin from the surface of neuronal cells in the hypothalamus. This blocks leptin from binding to its receptors.
Leptin circulates in blood and acts on the brain 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.
In a study of healthy women, an increase in carbohydrate consumption (40% excess energy as carbohydrates derived from bread, rice, biscuit, and sugar) resulted in plasma leptin levels increasing by 28% and an increase in 24-hour energy expenditure of 7%.
The circulating leptin level serves as a gauge for energy reserves and directs the central nervous system to adjust food intake and energy expenditure accordingly. Leptin exerts immediate effects by acting on the brain to regulate appetite (Figure 1).
Plasma leptin levels decrease during fasting[8] or energy restriction[9] and increase during refeeding,[10] overfeeding,[11] and surgical stress. [12,13] Insulin, glucocorticoids, serotonin, and estrogen have been reported to stimulate leptin secretion.
Frequency. Congenital leptin deficiency is a rare disorder. Only a few dozen cases have been reported in the medical literature.
Leptin has recently emerged as a key link between metabolic responses and inflammation. It is thought that the elevated levels of leptin in obese individuals can contribute to the low-grade chronic inflammation, on which degenerative diseases and autoimmune reactivity could possibly develop.
Interestingly, there is a close relationship between estrogen and leptin; estrogen is one of the important regulating factors in the metabolism of leptin [18, 19].
“But there's a lot you can do to reduce leptin resistance,” Dr. Sands says. Some dietary and lifestyle remedies for leptin resistance include: Consuming healthy fats such as olive oil, avocado, coconut, fish and grass-fed, pasture-raised animals.
The leptin blood test provides information concerning the level of leptin circulating in the body. Leptin is a hormone produced by fat cells in the body. It is the gatekeeper of fat metabolism, monitoring how much energy a person takes in.
In conclusion, our data show that in adult humans of different body weight, serum leptin gradually declines during aging; leptin reduction is higher in women than in men, but it is independent from BMI and other age-related endocrine changes.
This attracted a lot of interest toward the clinical use of leptin for the treatment of obesity in humans. However, most obese subjects are not deficient in the leptin gene, and the circulating levels of leptin are elevated compared to those in non-obese subjects.
Consequently, leptin resistance influences the stress response and increases cortisol production.
Conclusions: Leptin is a biomarker of stress, with a decrease following acute stress. Normal-weight individuals and women also have a higher variation of leptin levels after stress, suggesting that leptin may have implications in obesity development in response to stress in a sex-dependent manner.
Leptin has been shown to increase energy expenditure in particular through its effects on the cardiovascular system and brown adipose tissue (BAT) thermogenesis via the hypothalamus.