ReviewMetabolically healthy obesity from childhood to adulthood — Does weight status alone matter?☆
Introduction
Obesity prevalence has nearly doubled worldwide between 1980 and 2008 and still continues to increase. The largest increase in prevalence rates, especially during childhood and adolescence, has been lately seen in the African region as well as Europe [1].
Almost 10% of the world’s adult population presents with diabetes, with highest prevalence rates in the Eastern Mediterranean region as well as the American region [1].
Obesity is in general associated with significantly higher all-cause mortality during adulthood [2], and obesity during childhood and adolescence has been shown to significantly increase the risk for morbidity and mortality later in life [3]. Especially visceral obesity, defined as increased waist circumference and accumulation of adipose tissue in the abdomen, significantly increases the risk for cardiovascular or metabolic diseases, starting as soon as during puberty [4]. However, there is emerging evidence that some obese patients do not have the typical obesity-associated metabolic disorders, such as insulin resistance and glucose intolerance, arterial hypertension, or dyslipidemia. The phenomenon of metabolically healthy obese patients has been described almost 15 years ago [5], and prevalence rates for the MHO phenotype have been reported to vary between 10% and 34% [5], [6], [7], [8], [9]. MHO seems to be more prevalent in women than in men, and prevalence of MHO seems to decrease with age in both genders [10].
The aim of this review is to discuss the current literature and our current understanding of metabolically healthy obesity as well as underlying mechanisms and its effect on obesity-associated (long-term) morbidity from childhood over adolescence to adulthood.
Section snippets
Definition of metabolically healthy obesity
In most studies, metabolically healthy obesity has been suggested to be defined as obesity (BMI ≥ 30 kg/m2) with no indication for associated metabolic disorders, such as type 2 diabetes or dyslipidemia [5], [11], [12]. One classification presented within a review article suggests to use body fat content > 25% in men and 30% in women instead of BMI to define obesity [6]. One of the first studies to define the MHO phenotype has defined percentage body fat and insulin resistance as key components to
Underlying mechanisms defining disease or health
There is increasing evidence suggesting that (subclinical) inflammation could be the underlying mechanism that determines whether an obese individual is metabolically healthy or not and that categorizes the differences in metabolic profiles between subgroups of obesity [18]. (Subclinical) inflammation is associated with insulin resistance, and CRP has emerged as one of the best predictors of (vascular) inflammation, cardiovascular disease and the metabolic syndrome [22]. There is a strong
Healthy obese — Is there a pathophysiological explanation?
Human fat depots consist of several compartments, namely subcutaneous adipose tissue which is the most prominent, visceral fat covering the viscerum (omentum majus and around the liver and kidney) and intrahepatic fat as well as brown adipose tissue. Compared to subcutaneous fat which is mostly metabolically inactive, the visceral adipose tissue is endocrinologically active [36]. To date, more than 200 hormones are known to be secreted by the visceral adipocytes (so-called adipokines), and the
Different interventions strategies for MHO and non-MHO patients?
Such a concept would have direct impact on the development of appropriate interventions for healthy and non-healthy obese patients [39], [40]. One might hypothesize that metabolically healthy obese subjects do not need an intervention at all, whereas non-healthy obese or even metabolically non-healthy normal weight patients (if they have a substantial amount of visceral or hepatic fat) might require a lifestyle intervention. Recent studies show that aerobic exercise or hypocaloric diet may help
Metabolically healthy obesity during childhood and adolescence
Available data related to the MHO phenotype are mainly derived from studies in adults, as studies that have focused on MHO during childhood and adolescence are very limited to date. As in adult patients, there is no homogenous definition of MHO for the pediatric population: Suggested definitions for MHO in childhood and adolescence include (a) quartiles based on levels of insulin resistance determined by HOMA-IR index [46], (b) no or 1 cardiometabolic risk factor (MHO) or ≥ 1 (or ≥ 2,
Maintaining the MHO phenotype from childhood to adulthood — Are the beneficial effects later in life?
The longitudinal Bogalusa Heart study has examined 1098 individuals who participated as both children (aged 5–17 years) and adults (aged 24–43 years) between 1997 and 2002. Participants with the MHO phenotype during childhood were more likely to retain MHO status in adulthood. Despite the fact that the level of obesity and fat mass was still markedly increased in childhood and in adulthood, this group of MHO individuals (both, during childhood and in adulthood) showed a cardiometabolic profile
Metabolically healthy obesity during adulthood and impact on morbidity and mortality — Results from a meta-analysis
According to our current understanding, the classification of “metabolically benign obesity” or “metabolically healthy obesity” does only refer to metabolic or cardiovascular complications and does not take into account, that obesity may be associated with other, non-metabolic complications, such as orthopedic problems, pulmonary complications, psychological conditions, or others.
It is absolutely unclear to date, whether the MHO phenotype may modify or even resolve morbidity and mortality
Conclusion and future directive
To date, definition of metabolically healthy obesity is very heterogeneous, making comparison between studies difficult. A consistent, robust and standardized definition of metabolically healthy obesity is urgently needed, which should consider – beside features of the metabolic syndrome – the degree of visceral obesity, insulin sensitivity, inflammatory markers as well as the degree of liver fat (NAFLD). This may have important implications for clinical research and patient care alike.
Acknowledgment
Part of the work was supported by the Federal Ministry of Education and Research, Germany (Integrated Research and Treatment Center IFB “Adiposity Diseases”, FKZ: 01E01001).
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The authors disclose any potential conflict of interest.