Modulation of leptin resistance by food compounds

Mol Nutr Food Res. 2016 Aug;60(8):1789-803. doi: 10.1002/mnfr.201500964. Epub 2016 Mar 1.


Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound.

Keywords: Agouti-related peptide; Megalin; Proopiomelanocortin; Protein tyrosine phosphatase 1B.

Publication types

  • Review

MeSH terms

  • Agouti-Related Protein / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Caffeine / pharmacology
  • Eating
  • Food*
  • Hypothalamus / metabolism
  • Leptin / metabolism*
  • Low Density Lipoprotein Receptor-Related Protein-2 / metabolism
  • Neurons / metabolism
  • Neuropeptide Y / metabolism
  • Obesity / metabolism
  • Pro-Opiomelanocortin
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*
  • Receptors, Leptin / metabolism
  • Resveratrol
  • Saponins / metabolism
  • Stilbenes / metabolism
  • Taurine / metabolism
  • Triterpenes / pharmacology


  • Agouti-Related Protein
  • Leptin
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Neuropeptide Y
  • Receptors, Leptin
  • Saponins
  • Stilbenes
  • Triterpenes
  • Taurine
  • Caffeine
  • Pro-Opiomelanocortin
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • celastrol
  • Resveratrol