Time to Consider the “Exposome Hypothesis” in the Development of the Obesity Pandemic

Abstract

The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent the main contributors to the obesity problem, they are not able to fully explain all cases and current trends. In this context, a body of knowledge related to exposure to as yet underappreciated obesogenic factors, which can be referred to as the “exposome”, merits detailed analysis. Contrarily to the genome, the “exposome” is subject to a great dynamism and variability, which unfolds throughout the individual’s lifetime. The development of precise ways of capturing the full exposure spectrum of a person is extraordinarily demanding. Data derived from epidemiological studies linking excess weight with elevated ambient temperatures, in utero, and intergenerational effects as well as epigenetics, microorganisms, microbiota, sleep curtailment, and endocrine disruptors, among others, suggests the possibility that they may work alone or synergistically as several alternative putative contributors to this global epidemic. This narrative review reports the available evidence on as yet underappreciated drivers of the obesity epidemic. Broadly based interventions are needed to better identify these drivers at the same time as stimulating reflection on the potential relevance of the “exposome” in the development and perpetuation of the obesity epidemic.

The Immune Response in Adipocytes and Their Susceptibility to Infection: A Possible Relationship with Infectobesity

“…Additionally, there is evidence that supports the role of infected adipocytes in obesity, since some pathogens are able to dysregulate components (i.e., signaling pathways) of adipose tissues and participate in the development of obesity [ 1 , 4 ]. This theory maintains that some microorganisms are capable of inducing the obesogenic process [ 5 , 6 ], with adenovirus 36 being one of the most studied pathogens associated with obesity.…”

The Extent of Lifestyle-Induced Weight Loss Determines the Risk of Prediabetes and Metabolic Syndrome Recurrence during a 5-Year Follow-Up

“…However, even when a metabolically healthy obese phenotype can be maintained over a long period of time, obesity remains a risk factor for cardiovascular disease [ 37 ]. It is a well-known phenomenon that responses to treatment are heterogeneous, which, in line with the existence of diverse obesities [ 38 ], may influence long-term outcomes following weight loss [ 39 ]. Our data are in agreement with the Look AHEAD study that examined the effects of lifestyle intervention in a large cohort of participants with type 2 diabetes.…”

‘Obesities’: Position statement on a complex disease entity with multifaceted drivers

“…Whilst a pleiad of molecules with quite diverse profiles is involved in energy homeostasis, 34,35 the existence of additional as yet unidentified factors should not be discarded. 36,37 Therefore, the individual's genotype, adipotype, enterotype and microbiome interplays with macronutrient intake, appetite, metabolism and thermogenesis. The interactions of the genetic make-up and the other explained personal characteristics condition individualized responses to macronutrients, dietary patterns and lifestyle habits, which represent key factors for the comprehensive and holistic understanding of energy homeostasis and should be considered in the era of precision medicine.…”

“…Whilst a pleiad of molecules with quite diverse profiles is involved in energy homeostasis, 34,35 the existence of additional as yet unidentified factors should not be discarded 36,37 …”