Adipose Tissue Dysfunction in Obesity‑Induced Type 2 Diabetes: Mechanistic Insights and Therapeutic Opportunities
Wambui Kibibi J.
School of Natural and Applied Sciences Kampala International University Uganda
ABSTRACT
Obesity is the strongest modifiable driver of type 2 diabetes (T2D), yet the mechanistic bridge between excess adiposity and systemic dysglycemia is increasingly recognized as dysfunction of adipose tissue (AT) rather than fat mass per se. In health, subcutaneous white adipose tissue (WAT) expands via adipogenesis to safely store lipid, secretes insulin‑sensitizing adipokines, and communicates with liver, muscle, pancreas, brain, and immune cells to maintain fuel homeostasis. In obesity, this plasticity is exceeded, precipitating adipocyte hypertrophy, depot‑specific hypoxia, extracellular‑matrix remodeling and fibrosis, mitochondrial and endoplasmic‑reticulum stress, and chronic low‑grade inflammation (metaflammation). These insults drive insulin resistance, catecholamine resistance, dysregulated lipolysis, and ectopic lipid deposition with lipotoxic signaling, ultimately burdening hepatic glucose production, myocellular glucose uptake, and β‑cell function. Emerging insights into AT endocrine and paracrine factors classical adipokines (adiponectin, leptin), lipokines, cytokines, and extracellular vesicles highlight complex bidirectional cross‑talk across organs. Converging mechanisms suggest therapeutic opportunities: weight loss through lifestyle and surgery; insulin‑sensitizing agents (metformin, thiazolidinediones); incretin‑based poly‑agonists; SGLT2 inhibition; and investigational approaches targeting inflammation, fibrosis, mitochondrial quality control, and thermogenic/beige fat recruitment. Precision strategies that integrate depot heterogeneity, immunometabolic states, and multi‑omics phenotyping may enable individualized interventions that restore AT health rather than merely shrinking fat mass. This review synthesizes current concepts linking AT dysfunction with T2D pathogenesis, surveys therapeutic avenues from lifestyle to next‑generation pharmacology, and outlines outstanding questions for clinical translation.
Keywords: adipose tissue; insulin resistance; adipokines; immunometabolism; type 2 diabetes
CITE AS: Wambui Kibibi J. (2026). Adipose Tissue Dysfunction in Obesity Induced Type 2 Diabetes: Mechanistic Insights and Therapeutic Opportunities. IDOSR JOURNAL OF BIOCHEMISTRY, BIOTECHNOLOGY AND ALLIED FIELDS 11(1):57-62. https://doi.org/10.59298/IDOSR/JBBAF/2026/1025762