Abstract
The concept of heterogeneity among obese individuals in their risk for developing metabolic dysfunction and associated complications has been recognized for decades. At the origin of the heterogeneity idea is the acknowledgement that individuals with central obesity are more prone to developing type 2 diabetes and cardiovascular disease than those with peripheral obesity. There have been attempts to categorize subjects according to their metabolic health and degree of obesity giving rise to different obese and non-obese phenotypes that include metabolically unhealthy normal-weight (MUHNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Individuals belonging to the MHO phenotype are obese according to their body mass index although exhibiting fewer or none metabolic anomalies such as type 2 diabetes, dyslipidemia, hypertension, and/or unfavorable inflammatory and fribinolytic profiles. However, some authors claim that MHO is only transient in nature. Additionally, the phenotype categorization is controversial as it lacks standardized definitions possibly blurring the distinction between obesity phenotypes and confounding the associations with health outcomes. To add to the discussion, the factors underlying the origin or protection from metabolic deterioration and cardiometabolic risk for these subclasses are being intensely investigated and several hypotheses have been put forward. In the present review, we compare the different definitions of obesity phenotypes and present several possible factors underlying them (adipose tissue distribution and cellularity, contaminant accumulation on the adipose tissue, dysbiosis and metabolic endotoxemia imposing on to the endocannabinoid tone and inflammasome, and nutrient intake and dietary patterns) having inflammatory activation at the center.
Highlights
Obesity, defined by the World Health Organization (WHO) as abnormal or excessive fat accumulation that may impair health, constitutes a rising threat to public health and welfare [1]and has become an epidemic in both developed and developing countries
The metabolically unhealthy normal-weight (MUHNW) phenotype is characterized by a normal body mass index (BMI) (18.5–25 kg/m2 ) associated with reduced lean body mass and increased levels of adiposity and ectopic fat distribution, with augmented visceral adipose tissue (AT) and abdominal subcutaneous AT which is a distinctive feature of this category [36,37]
In 2014, Gauthier et al demonstrated the relationship of persistent organic pollutants (POPs) with the variation in metabolic risk observed among obese individuals showing that the metabolically healthy obese (MHO) phenotype is associated with lower plasma levels of POPs as compared with metabolically unhealthy obese (MUO) subjects [156]
Summary
Obesity, defined by the World Health Organization (WHO) as abnormal or excessive fat accumulation that may impair health, constitutes a rising threat to public health and welfare [1]. The existence of heterogeneity among obese subjects in what regards their cardiometabolic risk has come to light, with a subgroup of these individuals being reported to be more resilient to metabolic, inflammatory, and/or fibrinolytic dysfunctions and its associated complications [3,6,7,9,12,13,14,15,16,17]. Obesity closely associates with a chronic low-grade inflammation, triggered by metabolic surplus [23]. The list of triggers for AT inflammation is continuously growing and extends far beyond positive energy balance. This inflammatory signaling centered on the AT, with many possible culprits, leads to a vicious cycle that perpetuates AT dysfunction, hinders metabolic adaptation [28,29], and may be at the basis of unhealthy, opposed to heathy, obesity
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