Identification and Characterization of Metabolically Benign Obesity in Humans

Abstract

Background: Obesity represents a risk factor for insulin resistance, type 2 diabetes mellitus, and atherosclerosis. In addition, for any given amount of total body fat, an excess of visceral fat or fat accumulation in the liver and skeletal muscle augments the risk. Conversely, even in obesity, a metabolically benign fat distribution phenotype may exist.Methods: In 314 subjects, we measured total body, visceral, and subcutaneous fat with magnetic resonance (MR) tomography and fat in the liver and skeletal muscle with proton MR spectroscopy. Insulin sensitivity was estimated from oral glucose tolerance test results. Subjects were divided into 4 groups: normal weight (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared], Ͻ25.0), overweight (BMI, 25.0-29.9), obese-insulin sensitive (IS) (BMI, Ն30.0 and placement in the upper quartile of insulin sensitivity), and obese-insulin resistant (IR) (BMI, Ն30.0 and placement in the lower 3 quartiles of insulin sensitivity).Results: Total body and visceral fat were higher in the overweight and obese groups compared with the normal-weight group (PϽ.05); however, no differences were observed between the obese groups. In contrast, ectopic fat in skeletal muscle (PϽ.001) and particularly the liver (4.3%±0.6% vs 9.5%±0.8%) and the intima-media thickness of the common carotid artery (0.54±0.02 vs 0.59±0.01 mm) were lower and insulin sensitivity was higher (17.4±0.9 vs 7.3±0.3 arbitrary units) in the obese-IS vs the obese-IR group (PϽ.05). Unexpectedly, the obese-IS group had almost identical insulin sensitivity and the intima-media thickness was not statistically different compared with the normal-weight group (18.2±0.9 AU and 0.51±0.02 mm, respectively). Conclusions:A metabolically benign obesity that is not accompanied by insulin resistance and early atherosclerosis exists in humans. Furthermore, ectopic fat in the liver may be more important than visceral fat in the determination of such a beneficial phenotype in obesity.

Trends in Cardiovascular Health Metrics in Obese Adults: National Health and Nutrition Examination Survey (NHANES), 1988–2014

“…Obese participants who are free from cardiometabolic disease risk factors are termed “metabolically healthy obese.”9, 26 The existence of the metabolically healthy obese condition has been controversial27, 28, 29, 30; however, we have recently added some clarification to this issue by pointing out that conclusions rest heavily on the definition of metabolically healthy obese 31. We4, 5, 10 and others12, 13, 14 have shown that 1 or 2 metabolic syndrome traits confer increased risk of diabetes mellitus and CVD outcomes and that such persons are relatively insulin resistant.…”

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

“…This phenotype is referred in the literature as "metabolically healthy obesity" (MHO) and may account for around 30% of the obese population [60]. Interestingly, the MHO phenotype is characterized by a more favourable body fat distribution with lower visceral fat and greater subcutaneous fat [42], by a lower ectopic fat depot in the liver [61], and by a less inflammatory profile with lower levels of circulating inflammatory markers [14,42] compared to unhealthy obese phenotype. We have recently reported that the visceral adipose tissue of MHO phenotype is associated with lower activation of the NLRP3 inflammasome in infiltrating macrophages, and with a more favourable inflammatory and immunological profile compared to that of unhealthy obese phenotype [33] (Figure 3).…”

Metabolically healthy obesity and NAFLD

“…However, compared with their peers who are MAO, individuals with MHO have lower risk of all-cause and cause-specific mortality [2][3][4] . Furthermore, studies suggest that individuals with MHO have similar insulin sensitivity to lean individuals, as well as lower liver fat content and lower intimal-medial thickness of the carotid artery compared with individuals who are MAO 5,6 . Agreement on a universally accepted definition of MHO, however, would improve the design of future studies and would facilitate comparisons between studies.…”