The Association of Short-Chain Fatty Acids and Leptin Metabolism: A Systematic Review

Introduction: Leptin is an adipokine that can activate a chain of reactions in the hypothalamus to exert its functions. Extreme variations of leptin levels are associated with body dysfunction, which can be influenced by several factors. As the association of short-chain fatty acids (SCFA) and leptin have not been fully studied, it would be important to understand if SCFA is one more factor that affect leptin´s metabolism. Methods: A systematic search occurred at PubMed/Medline in March 2018. Inclusion criteria were primary articles in English, that measured leptin synthesis or signaling, as well as SCFA used as an intervention, mechanism or outcome of results. Results: This systematic search found 573 articles, which were assessed based on inclusion and exclusion criteria. This led to 36 included articles published between 2002 and 2018: most studies were performed in animals (24), followed by in vitro studies (8) and human studies (4). In vitro studies showed that SCFA stimulate leptin expression in adipocytes through activation of FFAR3. Animal studies represent a realistic approach, considering the complex metabolism that leptin and SCFA have in the body. The interventions to modulate high-fat diets´ outcomes mostly caused a decrease in leptin concentration and increased in SCFA, added to suppressed body weight – which seems to be the most relevant factor that impacts leptin production. Moreover, SCFA and leptin levels might be related through different pathways, such as AMPK, PKA and PPAR-γ. The improvement in the quality of the microbiota can also play a role in this association. Human studies had very diverse sample and methods, though they also show that leptin is mainly correlated with adiposity, but microbiota also takes part in it. Conclusion: The current systematic review shows that the association between SCFA and leptin is not completely clear but occurs mainly through the activation of FFAR3 in adipocytes. Leptin expression depends on many factors, mainly body fat, which is predominant comparing to other influences, such as FFAR3 activation. Interventions that improve dysbiosis and balance SCFA production can have positive outcomes on leptin levels.