Leptin

Leptin is an adipokine (hormone produced by adipose tissue) that signals satiety to the hypothalamus — suppressing appetite and increasing energy expenditure. Leptin resistance (elevated leptin with impaired signaling) is a hallmark of obesity, paralleling insulin resistance. The gut microbiome modulates leptin sensitivity through endotoxemia-driven inflammation and SCFA signaling.

Microbiome-Leptin Axis

  • Dysbiosis → endotoxemia → chronic low-grade inflammation → impaired leptin receptor signaling → leptin resistance → overeating → obesity → more adipose → more leptin → deeper resistance.
  • SCFAs (especially propionate) stimulate leptin secretion from adipocytes via GPR41.
  • Heavy metal exposure (cadmium, lead) disrupts adipose function and leptin signaling [1].
  • High-fat diet alters gut microbiota and leptin/estrogen signaling in precocious puberty models [2].

Cross-References

References (4)

  1. ★Karen Pendergrass (2026). Heavy Metals, Microbial Metallomics, and the US Obesity Epidemic: A Mechanistic Examination of a Population-Level Metabolic Disruption. Zenodo Preprint. doi:10.5281/zenodo.18434951
  2. Nan Wu, Ke Ning, Yanan Liu et al. (2025). Wu 2025 — Relationship between High-Fat Diet, Gut Microbiota, and Precocious Puberty: Mechanisms and Implications. Frontiers in Microbiology. doi:10.3389/fmicb.2025.1564902
  3. Dominic Salamone, Angela Albarosa Rivellese, Claudia Vetrani (2021). Salamone 2021 — The Relationship between Gut Microbiota, Short-Chain Fatty Acids and Type 2 Diabetes: The Role of Dietary Fibre. Acta Diabetologica. doi:10.1007/s00592-021-01727-5
  4. Arpana Gupta, Vadim Osadchiy, Emeran A. Mayer (2020). Gupta, Osadchiy & Mayer 2020 — Brain-Gut-Microbiome Interactions in Obesity and Food Addiction. Nature Reviews Gastroenterology & Hepatology. doi:10.1038/s41575-020-0341-5

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