Adenovirus 36 infection and obesity risk: current understanding and future therapeutic strategies

ABSTRACT

Introduction

Obesity, a multifactorial disease caused by the interaction between genetic characteristics, metabolism, lifestyle, and environmental factors, is a major global health problem and is currently defined as a pandemic phenomenon. This disease is determined by an interaction of several factors, but the imbalance between energy consumption and expenditure seems to be the crucial point. In some cases, there is no linearity between exposure to those factors that cause the onset of obesity. A striking example of the occurrence of obesity despite no obvious risk factors is that of obesity induced by viral infections. The most important of such viruses appears to be human adenovirus 36 (Adv36).

Areas covered

This review covers the relation between obesity and infection by Adv36 in humans. Also, discussed are the opportunities of prevention or treatment for the effects of Adv36 in human body.

Expert opinion

The role of Ad36 in the development of obesity has already been established. Future research should focus on the development of vaccines against this agent, drug discovery for infected individuals, and effective therapeutic uses of E4orf1 gene protein for diabetes and other diseases in clinical practice.

KEYWORDS:

• Adipocytes and tissue
• E4orf1 gene
• glucose metabolism
• vaccines

Article highlights

• Human adenovirus 36 (Adv36) causes obesity in animals

• Adv36 antibodies demonstrate prior infection and are present in about 30% of people with obesity across the world

• Adv36 antibodies correlate with the presence of obesity in humans

• Adv36 acts directly on cells to promote hypertrophy and hyperplasia of adipose tissue

• The E4orf1 gene of Adv36 produces a protein that is responsible for the adipogenesis and other actions

• The E4orf1 protein acts through the Ras pathway to stimulate PI3K pathway facilitating production of GLUT1 and GLUT4 glucose transporters in the cell membrane to enhance glucose transport

• Adv36 enhances several lipogenic hormones in multiple tissues of the body

• A vaccine for Adv36 has been shown to be effective in animals in preventing virus-induced obesity but has not been commercially successful

• Some drugs and natural products have shown modest success in animals or in vitro in reducing Adv36-induced obesity

• The E4orf1 protein acts independently of insulin to lower blood glucose and a patent currently exists to develop a treatment for diabetes and its complications

Declaration of interest

RL Atkinson formerly owned patents for diagnostic tests and vaccines for adenovirus, but this company is no longer active and patents abandoned. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.