An alternative neural basis underlying leptin resistance.

ABSTRACT: Overconsumption of a palatable Western diet, a condition linked to central leptin resistance, contributes extensively to the current obesity epidemic. In this context, intensive efforts have focused on detailing the molecular mechanisms underlying leptin resistance. Here, we demonstrate that chronic inhibition of hypothalamic arcuate GABAergic neurons (Arc^GABA) effectively reduced diet-induced obesity (DIO). Interestingly, palatable food exposure increased the activity level of Arc^GABA neurons, which do not express the leptin receptor (non-LepR neurons; nonresponsive to leptin). Chronic activation of Arc^GABA non-LepR neurons led to massive obesity, which was associated with normal leptin-induced pSTAT3 signaling but phenotypic leptin resistance; i.e., high

SUBMITTER: Li H 

PROVIDER: S-EPMC12337207 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature