Infectious Mechanisms in Obesity Pathogenesis

Obesity is increasingly recognised as a multifactorial condition in which infectious agents contribute alongside genetic, dietary and environmental factors. Certain viruses, most notably human adenovirus-36 (HAdV-36), have been shown to directly promote adipocyte differentiation and lipid accumulation. Viral proteins such as E4orf1 can hijack host signalling cascades, including the PI3K–Akt–mTOR and Ras pathways, to favour glucose uptake and adipogenesis. Persistent or repeated infections may also drive chronic low-grade inflammation through sustained interferon responses, altering lipid metabolism and immune regulation. Collectively, these mechanisms suggest that pathogens can play a causal or co-factorial role in the initiation and progression of obesity, with potential implications for novel therapeutic targets and public-health interventions.

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Infectious Mechanisms in Obesity Pathogenesis publication trend

The graph below shows the total number of articles in infectious mechanisms in obesity pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Adipogenesis: The process by which preadipocytes differentiate into lipid-laden adipocytes under the control of transcription factors such as PPARγ.

E4orf1: A viral protein encoded by adenovirus-36 that subverts host PDZ-domain proteins to activate PI3K–Akt signalling and promote glucose uptake.

PI3K–Akt–mTOR pathway: A central intracellular signalling cascade regulating cell growth, metabolism and survival, frequently targeted by pathogens to alter host nutrient flux.

Human adenovirus-36 (HAdV-36): A viral species linked epidemiologically and experimentally to increased adiposity, capable of altering host lipid and glucose metabolism.

Interferon (IFN) signalling: An innate immune response to viral infection involving type I and III IFNs that can chronically influence adipose-tissue inflammation and metabolic balance.

References

1. E4orf1: The triple agent of adenovirus – Unraveling its roles in oncogenesis, infectious obesity and immune responses in virus replication and vector therapy. Tumour Virus Research (2024).
2. An Observational Study Suggests That Natural HAdV-36 Infection Decreases Blood Glucose Levels without Affecting Insulin Levels in Obese Young Subjects. Viruses (2024).
3. Viral Infections and Interferons in the Development of Obesity. Biomolecules (2019).
4. E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes: A Template to Improve Steatosis & Hyperglycemia. PLOS ONE (2012).
5. The Human Adenovirus E4-ORF1 Protein Subverts Discs Large 1 to Mediate Membrane Recruitment and Dysregulation of Phosphatidylinositol 3-Kinase. PLOS Pathogens (2014).