The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education. Keywords: metabolically healthy but obese; insulin sensitivity; body composition; metabolic risk factors; cardiovascular diseases Introduction Obesity has been increasing at a rapid rate over the past decades and has now reached epidemic proportions. Recent data suggest that 65% of US adult are overweight (body mass index425 kg m À2) and 30% are obese (body mass index430 kg m À2).1 Obesity is associated with numerous metabolic complications such as Type 2 diabetes, dyslipidemia, hypertension, cardiovascular diseases and several forms of cancer. 2 The risk of developing obesity-related complications is proportional to the degree of obesity, and more specifically to android fat accumulation. 3 However, the presence of these obesity-related metabolic disturbances varies widely among obese individuals. 4,5 Accordingly, a unique subset of obese individuals has been described in the medical literature that seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. 6-12 These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display favorable metabolic profiles characterized by high levels of insulin sensitivity, no hypertension, as well as favorable lipid, inflammation, hormonal, liver enzyme and immune profiles 7,9,[13][14][15] ( Figure 1). This phenomenon has also been observed in adolescents. 16 Despite a clinical awareness of the MHO individu...

These data show that both DNA methylation and gene expression are responsive to caloric restriction and provide new insights about the molecular pathways involved in body weight loss as well as methylation regulation during adulthood.

Some insulin-resistant obese postmenopausal (PM) women are characterized by an android body fat distribution type and higher levels of lean body mass (LBM) compared to insulin-sensitive obese PM women. This study investigates the independent contribution of LBM to the detrimental effect of visceral fat (VF) levels on the metabolic profile. One hundred and three PM women (age: 58.0 ± 4.9 years) were studied and categorized in four groups on the basis of their VF (higher vs. lower) and lean BMI (LBMI = LBM (kg)/height (m 2 ); higher vs. lower). Measures included: fasting lipids, glucose homeostasis (by euglycemic/hyperinsulinemic clamp technique and 2-h oral glucose tolerance test (OGTT)), C-reactive protein (CRP) levels, fat distribution (by computed tomography (CT) scan), and body composition (by dual-energy X-ray absorptiometry). Women in the higher VF/higher LBMI group had lower glucose disposal and higher plasma insulin levels compared to the other groups. They also had higher plasma CRP levels than the women in the lower VF/lower LBMI group. VF was independently associated with insulin levels, measures of glucose disposal, and CRP levels (P < 0.05). LBMI was also independently associated with insulin levels, glucose disposal, and CRP levels (P < 0.05). Finally, significant interactions were observed between LBMI and VF levels for insulin levels during the OGTT and measures of glucose disposal (P < 0.05). In conclusion, VF and LBMI are both independently associated with alterations in glucose homeostasis and CRP levels. The contribution of VF to insulin resistance seems to be exacerbated by increased LBM in PM women.

No abstract