2nd Edition of International Obesity and Metabolism Conference 2026

Abstract

BACKGROUND: Obesity is a complex, multifactorial metabolic disorder characterised by excessive adipose tissue accumulation and chronic low-grade systemic inflammation. Once regarded solely as an energy reservoir, adipose tissue is now recognised as a dynamic endocrine organ that secretes bioactive adipokines — including leptin, adiponectin, and resistin — which govern appetite, insulin sensitivity, lipid metabolism, and inflammatory responses. Dysregulation of adipose-derived signals is central to the pathogenesis of insulin resistance and the constellation of obesity-related comorbidities, including type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease.

OBJECTIVES: This review aimed to (1) elucidate the molecular mechanisms underlying key adipose tissue signalling pathways; (2) examine inter-organ crosstalk between adipose tissue, liver, skeletal muscle, brain, and gut; and (3) identify existing and emerging therapeutic targets within these pathways relevant to obesity management.

METHODS: A comprehensive narrative review was conducted using PubMed and Scopus databases. Articles published between 2000 and 2025 were systematically searched using terms related to adipose tissue, signalling pathways, insulin resistance, and obesity therapeutics. Data synthesis integrated findings from in vitro adipocyte models, in vivo animal studies, and human clinical investigations.

RESULTS: Critical impairments were identified across multiple interconnected pathways in obese adipose tissue. Disruption of insulin/PI3K-Akt signalling promotes glucose uptake failure and lipogenesis dysregulation. Leptin resistance — characterised by elevated circulating leptin with loss of satiety signalling via JAK2/STAT3 — perpetuates hyperphagia. Reduced adiponectin-mediated AMPK activation impairs insulin sensitisation and exacerbates inflammation. Concurrent upregulation of NF-κB and TNF-α inflammatory pathways drives macrophage infiltration and systemic metabolic dysfunction. Hyper-activated mTOR signalling further suppresses autophagy and promotes anabolic lipid accumulation. Dysregulation of brown/beige adipose tissue thermogenic capacity, mediated via UCP1, was also identified as a key contributor to impaired energy expenditure.

CONCLUSION; Adipose tissue signalling pathways represent a convergent therapeutic frontier in obesity. Emerging strategies — including GLP-1 receptor agonists, AMPK activators, nutraceuticals (resveratrol, curcumin), gene-editing approaches (CRISPR-Cas9), and adipose browning inducers — hold significant promise for restoring metabolic homeostasis. Integrating mechanistic molecular understanding with clinical translation is imperative for the development of personalised, pathway-targeted obesity therapeutics.