Is there a paradox in obesity?

Abstract

In an industrialized society, the increase in obesity incidence has led to an increase in premature morbidity and mortality rates. There is a relationship between body mass index (BMI) and the increased incidence of hypertension, dyslipidemia, type 2 diabetes mellitus, and cardiovascular disease, an increase in mortality. However, obese individuals with these conditions may have better outcomes than their lean counterparts, thus the term "obesity paradox." Most studies supporting this paradox are cross-sectional and do not take into account the quantity or type of adiposity, the disease severity, and comorbidities. Although BMI is an indicator of the amount of body fat, it does not differentiate between adiposity types. Adipocytes that are highly functional have good fuel storage capacity are different from adipocytes found in visceral obesity, which are poorly functioning, laden with macrophages, and causing low-grade inflammation. Individuals with high BMI may be physically fit and have a lower mortality risk when compared with individuals with a lower BMI and poorly functioning adiposity. We review the complexity of adipose tissue and its location, function, metabolic implications, and role in cardiovascular morbidity and mortality. The terminology "obesity paradox" may reflect a lack of understanding of the complex pathophysiology of obesity and the association between adiposity and cardiovascular disease.

Figure 1. Illustration of complex and multi-organ relationship between excessive nutrients and neuronal dysregulation responsible for obesity and cardiovascular disease

Excessive caloric intake, along with gut microbiota, play a role in obesity and CVD. Visceral adiposity is characterized by increased adipose mass and macrophages that together produce pro-inflammatory adipokines and cytokines adversely affecting the cardiovascular system. Increased visceral adiposity also causes hyperleptinemia and hyperinsulinemia that are poorly regulated by the brain, perpetuating increased caloric intake. Insulin resistance and the increased FFA flux cause dyslipidemia with increased VLDL, triglycerides and decreased HDL-cholesterol which together with chronic low-grade inflammation results in CVD. CVD, cardiovascular disease; hS–CRP, highly sensitive C-reactive protein; FFA, free fatty acid; FGF 21, fibroblast growth factor 21; HDL, high density lipoprotein; VLDL, very low density lipoprotein

Figure 2. Proposed relationship between body mass index and mortality rate

The J-shaped curve illustrates increased mortality rate with a high body mass index (BMI) and with a very low BMI. The “sweet spot” depicts an ideal BMI, approximately 21 to 24 kg/m² in women and 22 to 25 kg/m² in men. Ethnic, racial and gender variations are not shown. The arrow shows the obesity paradox in individuals with cardiovascular disease. A mitigating effect of a higher BMI on mortality is shown by points A and B. Point “B” conceptualizes a population with higher BMI but lower mortality as compared to matched population shown as point “A” with a lower BMI but higher mortality.