Hypothalamic neuroimmune remodeling as an immunometabolic bridge between childhood obesity and earlier pubertal onset.

Narrative review synthesizing evidence on immune-endocrine crosstalk in childhood obesity and precocious puberty

“This review systematically synthesizes current evidence on this immune-endocrine crosstalk and describes how peripheral immune signals may remodel the hypothalamic microenvironment and alter pubertal timing.”

Children with childhood obesity and central precocious puberty (CPP)

“While the link between childhood obesity and central precocious puberty (CPP) is well documented, the immune-mediated mechanisms that may precipitate earlier pubertal onset remain incompletely understood.”

Hypothalamic neuroimmune remodeling is proposed as a mechanism linking chronic low-grade peripheral inflammation to earlier activation of the hypothalamic-pituitary-gonadal axis.

“This review proposes hypothalamic neuroimmune remodeling as a candidate immunometabolic bridge through which chronic low-grade peripheral inflammation may influence the timing of hypothalamic-pituitary-gonadal (HPG) axis activation.”

Peripheral inflammatory signals from adipose tissue, lipotoxicity, and gut dysbiosis may reach the central nervous system via the arcuate nucleus-median eminence complex, blood-brain barrier disruption, and gut-brain pathways.

“Peripheral inflammatory signals may reach the central nervous system through the arcuate nucleus-median eminence complex, disruption of the blood-brain barrier, and immune-mediated gut-brain pathways.”

Local neuroimmune responses involving glial cells may alter the excitability of the kisspeptin-GnRH network, potentially lowering the threshold for pubertal onset.

“This localized neuroimmune response may alter the excitatory milieu and synaptic connectivity of the kisspeptin-GnRH network, thereby lowering the threshold for HPG axis activation.”

The causal role of neuroimmune remodeling in obesity-associated pubertal advancement requires further validation through targeted mechanistic studies and longitudinal immunophenotyping.

“Although neuroimmune remodeling represents a plausible mechanism underlying obesity-associated pubertal advancement, its causal role requires further validation through targeted mechanistic studies and longitudinal immunophenotyping.”