Introduction
Epidemiological studies indicate the dramatic escalation of non-communicable diseases, namely type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and cancer all over the world in the past decades. Available evidence points to the current obesity epidemic as the principle cause of this health crisis. Actually, current data have suggested that obesity is responsible for almost one in five cases of overall mortality.1 Moreover, significant correlations between diabetes and obesity have been reported, while obese individuals exhibit a greater risk of developing CVD.2
Obesity is a multifaceted disorder with a complex pathophysiology as the related metabolic abnormalities largely arise from excess fat accumulation, insulin resistance and low-grade systemic inflammation.1 3 Interestingly, a subset of obese individuals with normal metabolic profile have been identified and described as metabolically healthy obese (MHO). The main problem in estimating the prevalence of MHO is the lack of consensus regarding its definition.4 The need for harmonising MHO definitions has been addressed recently by the BioShare-European Union project, to characterise clinical and metabolic factors associated with MHO and compare key characteristics defining MHO.5 Although they have excess adipose tissue, they seem to be protected from obesity-related abnormalities, such as hyperinsulinaemia, dyslipidaemia, hypertension and diabetes.6 7 The prevalence of MHO is approximately 20%–30% among the obese depending on the studied cohort and the exact definition of the metabolic disturbance.6 8 It is also well established that MHO is more common in certain populations, such as women, younger adults and people with European descent.9 A common definition in accordance with the guidelines of the American Heart Association (AHA) considers MHO (<3 risk factors) and metabolically unhealthy obese (MUO) (≥3 risk factors or physician diagnosed diabetes and/or use of medications) based on the following criteria: waist circumference, ≥88 cm female, ≥102 cm male; triglycerides ≥1.7 mmol/L; high-density lipoprotein (HDL) cholesterol<1.03 mmol/L male, 1.3 mmmol/L female; systolic BP ≥130 mm Hg and/or diastolic BP ≥85 mm Hg; fasting blood glucose ≥5.6 mmol/L.10 Alternatively, recent recommendations call for stricter criteria, that is, 0 of the above listed metabolic criteria with the exclusion of waist circumference.11 In fact, more than 30 distinct definitions have been applied in clinical and research studies in the field.9 The majority of these investigations used the AHA or its alternative criteria mentioned above, but other components have also been included, such as C reactive protein (CRP), 2-hour blood glucose level during an oral glucose tolerance test and insulin sensitivity/resistance.4
Although some evidence indicates that the risk of CVD and mortality of MHO individuals is similar to what is expected in lean healthy controls, others have concluded that obesity per se regulates the risk of morbidity and mortality.7 12–14 First, an observational study reported that MHO did not increase CVD risk, while both lean and obese subject with two or more metabolic abnormalities experienced a greater hazard.15 This evidence indicates that metabolic disruption is a more important determining factor of morbidity and mortality than body fatness. On the other hand, Bell et al16 conducted a meta-analysis on the relationship between obesity and diabetes and concluded that regardless of metabolic health status, the risk of diabetes was elevated by fourfold in obese participants after adjustment for sociodemographic covariates compared with the normal weight cohort. However, it is increasingly evident that additional characteristics, such as cardiorespiratory fitness (CRF) should be considered to accurately describe the MHO phenotype and its health hazards.2
To summarise the current evidence, it appears that although they may exhibit somewhat elevated risk compared with healthy lean individuals, people with MHO are protected against cardiometabolic disorders relative to their MUO counterparts.17 This review does not intend to discount the benefits of weight loss in health enhancement and certainly does not consider MHO a benign condition, but highlights the vital role of physical activity (PA) and CRF improvement in a multidisciplinary obesity treatment. Although, PA interventions result only in modest weight loss, the increased energy expenditure leads to the reduction of fat mass.3 18 Most importantly, the majority of the studies that analysed the relationship between mortality and metabolic health in obesity have not adjusted for CRF. When CRF was accounted for, no difference in mortality rate has been evident between MHO and normal weight individuals,11 19 thus as opposed to fatness the level of CRF is primarily responsible for the variances between these phenotypes.7 The most significant conclusion in the fatness versus fitness debate supports the notion that CRF cannot be excluded as a significant predictor of cardiovascular and metabolic health, because compared with high body mass index (BMI), low CRF has a larger impact on mortality risk.18 However, despite the increased attention and accumulating data in the past years, the underlying mechanisms of the MHO phenotype are not completely understood. There is an emerging consensus to shift the focus from body weight-centred approaches to lifestyle factors and more relevant metabolic/cardiovascular health parameters, such as CRF. Experts also recommend including CRF improvement as a primary end point of obesity treatment plans.18–21 This review emphasises the central role of PA and CRF by summarising the most current data that emerged since a systematic review, meta-analysis and other experts’ opinions on this topic.17 19 20
A narrative review of the literature was conducted with articles screened via PubMed, Embase and Scopus databases, using the following keywords and their combinations: “obesity”, “metabolic health”, “metabolically healthy obesity”, “metabolically unhealthy obesity”, “cardiorespiratory fitness”, “physical activity” and “exercise”. The reference lists of the relevant articles were also scanned for additional information.