The INDIVIDUALIST

A Wiki about biochemical individuality

Nutrigenomics

See Also

Description

Leptin in an important component in the long term regulation of body weight. Genetically obese mice with inactivating mutations in the ob gene or the gene encoding the leptin receptor (db gene) have been known for many years and were instrumental in the initial cloning of the ob gene. Recent studies with obese and non-obese humans demonstrated a strong positive correlation of serum leptin concentrations with percentage of body fat, and also that there was a higher concentration of ob mRNA in fat from obese compared to thin subjects. It appears that as adipocytes increase in size due to accumulation of triglyceride, they synthesize more and more leptin. In essence, leptin provides the body with an index of nutritional status.

Leptin is released by fat cells in amounts mirroring overall body fat stores. Thus, circulating leptin levels give the brain a reading of energy storage for the purposes of regulating 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.

Although leptin is a circulating signal that reduces appetite, in general, obese people have 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. Thus, obesity develops when people take in more energy than they use over a prolonged period of time, and this excess food intake is not driven by hunger signals, occurring in spite of the anti-appetite signals from circulating leptin. The high sustained concentrations of leptin from the enlarged fat stores result in the cells that respond to leptin becoming desensitised.

Genomics

  • LEP leptin (obesity homolog, mouse) [Homo sapiens]
  • GeneID: 3952 Primary source: HGNC:6553
  • Official Symbol: LEP and Name: leptin (obesity homolog, mouse)
  • Gene type: protein coding
  • Gene name: LEP
  • Gene description: leptin (obesity homolog, mouse)
  • Organism: Homo sapiens
  • Gene aliases: OB; OBS
  • Chromosome: 7; Location: 7q31.3
Summary

This gene is similar to the mouse obesity gene (ob). The protein encoded by this gene is secreted by white adipocytes. In the mouse study, mutations in this gene are linked to severe and morbid obesity.

Literature review

Leptin is generally thought to play a key role in the regulation of eating. The role of leptin in the regulation of eating in obese binge- and non-binge-eating women during exposure to food and food-related stimuli.(1)

A significant correlation between BMI and leptin was found in the two fat tissue compartments of both genders, but the correlation between BMI and TNFalpha was found only in subcutaneous fat tissue of women.(2)

Body fat distribution does not serve as a predictor of leptin levels in postmenopausal women.(3)

High leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity. (4)

Results suggest that leptin is released within the brain and at an increased rate in obese humans, in whom activation of brain serotonergic and neuropeptide Y mechanisms also exists. (5)

Over the 8-month intervention period, regardless of group membership, youths who had the lowest increase in cardiovascular fitness tended to have the highest increase in leptin. (6)

Polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin. (7)

Attribution

References

.