Neuro-Adipose Signaling Pathways: How Brain–Adipose Communication Breakdowns Lead to Diabesity

Nassimbwa Kabanda D.

Faculty of Medicine Kampala International University Uganda

                                                                                         ABSTRACT
Adipose tissue and the brain are linked by dense neuroendocrine circuits that continuously coordinate appetite, energy expenditure, thermogenesis and glucose–lipid handling. This bidirectional “brain–fat axis” uses sympathetic and sensory nerves, together with circulating adipokines and gut-derived signals, to match fuel availability with storage and oxidation. In obesity, this communication progressively fails. Hypothalamic and brainstem networks that normally integrate leptin, insulin and nutrient cues become inflamed and resistant; sympathetic and sensory innervation of white and brown adipose tissue (WAT, BAT) is remodeled; and adiposederived endocrine and immune signals feed back to further impair central control. The result is a self-reinforcing state of “diabesity,” where chronic positive energy balance, adipose dysfunction and type 2 diabetes (T2D) become tightly coupled.This review frames diabesity as a disorder of neuro–adipose signaling. First, we outline
the anatomical and molecular architecture of brain–adipose circuits, emphasizing sympathetic efferents, emerging roles of PIEZO2-positive sensory afferents and key adipokine pathways. We then summarize how hypothalamic and brainstem nuclei use these channels to regulate lipolysis, adipogenesis, browning and thermogenesis in WAT and BAT. Next, we examine how obesogenic diets, chronic overnutrition and stress
trigger hypothalamic inflammation, leptin and insulin resistance, and degeneration or functional impairment of adipose innervation. These changes uncouple caloric intake from expenditure and disrupt adipose endocrine outputs, promoting ectopic lipid deposition, insulin resistance and β-cell stress. Finally, we discuss emerging strategies to restore brain–adipose communication, including weight loss, structured sleep and circadian alignment, pharmacologic leptin and GLP-1–based therapies, and experimental neuromodulation of sympathetic outflow or adipose sensory circuits. We highlight open questions around human adipose innervation, sex- and depot-specific neuro–adipose wiring, and how to integrate neurobiological measures into precision care for obesity-related T2D.

Keywords: neuro–adipose axis; sympathetic innervation; hypothalamic inflammation; leptin resistance; diabesity

CITE AS: Nassimbwa Kabanda D. (2026). Neuro-Adipose Signaling Pathways: How Brain-Adipose Communication Breakdowns Lead to Diabesity. NEWPORT INTERNATIONAL JOURNAL OF PUBLIC HEALTH AND PHARMACY,7(1):107-116.
https://doi.org/10.59298/NIJPP/2026/71107116