Metabolic Reprogramming in Obesity-Linked Cancers: Interplay with Diabetic Pathophysiology

Kato Jumba K.

Faculty of Science and Technology Kampala International University Uganda

ABSTRACT

The global escalation of obesity and type 2 diabetes mellitus (T2DM) has unveiled a troubling nexus with cancer development and progression. Obesity-linked cancers, including those of the breast, colon, pancreas, liver, and endometrium, share metabolic hallmarks driven by the intricate reprogramming of cellular energy pathways. This metabolic reprogramming facilitates cancer cell survival, proliferation, and immune evasion under the altered systemic conditions created by obesity and diabetes. Central to this pathological triad is insulin resistance, hyperinsulinemia, and chronic inflammation, which together disrupt adipokine signaling, stimulate oncogenic insulin/IGF pathways, and foster a pro-tumorigenic microenvironment. Additionally, excess lipid availability and mitochondrial dysfunction in obese-diabetic states fuel aberrant glycolysis, lipogenesis, and glutamine metabolism, hallmarks of cancer cell metabolic flexibility. This review critically examines the intersection of obesity-induced metabolic alterations and diabetic pathophysiology in driving cancer progression, emphasizing key regulatory molecules such as HIF-1α, mTOR, AMPK, and SREBP-1. We also discuss emerging therapeutic interventions targeting metabolic pathways, such as metformin, PPAR agonists, and lipid metabolism inhibitors, offering promising directions for managing obesity-associated malignancies. Understanding the metabolic crosstalk between obesity, diabetes, and cancer may yield novel biomarkers and intervention strategies with potential for precision oncology.

Keywords: Obesity, Type 2 Diabetes Mellitus, Cancer Metabolism, Metabolic Reprogramming, Insulin Resistance

CITE AS: Kato Jumba K. (2025). Metabolic Reprogramming in Obesity-Linked Cancers: Interplay with Diabetic Pathophysiology. NEWPORT INTERNATIONAL   JOURNAL OF SCIENTIFIC AND   EXPERIMENTAL SCIENCES 6(3):212-220 https://doi.org/10.59298/NIJSES/2025/63.212220