Proceedings of the National Academy of Sciences · 2018 · 48 citations · 54 references
Life SciencesBiochemistryEndocrinologyMetabolic RegulationMetabolismNutritional BiochemistryAppetiteAppetite RegulationFatty Acid MetabolismHormonal Control Of MetabolismLipid MetabolismMetabolic EndocrinologyBody Weight RegulationEndocannabinoid MetabolismEndocannabinoid SignalingEndocannabinoid SystemIntegration Of Hormonal SignalsLeptin ResistanceLeptin SignalingMetabolic Modulation
Significance We present evidence that an endocannabinoid-dependent signaling mechanism contributes to the hypophagic actions of leptin. Specifically, leptin increases fatty acid amide hydrolase (FAAH) activity and reduces N -arachidonoylethanolamine (anandamide; AEA) signaling, particularly within the hypothalamus, to promote a suppression of food intake. This mechanism is lost in diet-induced obesity and is furthermore modulated by a human genetic variant (C385A) of the FAAH gene. As such, reduced sensitivity to leptin in FAAH 385A-allele carriers may contribute to their higher risk to develop obesity and related metabolic complications.
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