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 pendergrass 2026 heavy metals obesity epidemic.
- High-fat diet alters gut microbiota and leptin/estrogen signaling in precocious puberty models wu 2025 high fat diet gut microbiota precocious puberty.
Cross-References
- obesity — leptin resistance as central mechanism
- insulin resistance — parallel hormone resistance
- endotoxemia — inflammation drives leptin resistance
- adiponectin — complementary adipokine (insulin-sensitizing)