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      Response: Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status ( Endocrinol Metab 2015;30:185-94, Tae Hoon Lee et al.)

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      Endocrinology and Metabolism
      Korean Endocrine Society

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          Abstract

          First, we wish to express our great thanks to Prof. Kim for choosing our article and for noting an important point in our study. During the past few years, metabolically healthy obesity (MHO) has been a hot topic of debate in the field of obesity because its definition differs slightly from that of metabolic syndrome and because the inclusion of insulin resistance and systemic inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) in its definition is advantageous [1]. However, recently published review articles and meta-analyses have argued against the existence of MHO as a specific phenotype of obesity [2 3 4]. These review papers are skeptical about the existence of "healthy obesity" in terms of the development of cardiovascular disease, mortality, and diabetes. The reason for this discrepancy could be due to differences in ethnicity or study populations. However, the main reasons are thought to be the absence of a unified definition of MHO and differences in the duration of time that the subjects had been "metabolically healthy" and "obese" among individual studies. A very recent article by Hamer et al. [5] discussed the stability of MHO. They followed 2,422 participants in the English Longitudinal Study of Ageing for a median of 8 years and found that 44.5% of healthy obese people had transitioned into an unhealthy state, compared with only 16.6% and 26.2% of healthy adults of normal weight and overweight adults, respectively. These results suggest that a healthy obese phenotype is relatively unstable. Based on these results, we must consider not only the current status of a patient with MHO, but also how long the patient has had an MHO or obese status; a considerable portion of those with MHO might convert to a metabolically unhealthy obese status during the follow-up secondary to the deleterious effects of obesity itself. In our study published in volume 30, issue 2 of Endocrinology and Metabolism (EnM), we showed that among the adipocytokines measured in our study subjects, high concentrations of tumor necrosis factor α and adipocyte fatty acid binding protein were significantly associated with metabolically unhealthy status in non-obese individuals [6]. Although MHO is being discussed more than other phenotypes, we focused on the concentrations of these adipocytokines in metabolically unhealthy non-obese subjects. Based on the results of our paper, we can assume that increased adipocytokine concentrations serve as an indicator for determining metabolic health in these subjects, as shown in previous studies [7 8]. We recommend the inclusion of these adipocytokine levels in the definition of metabolic health, if possible. Unfortunately, we could not analyze the statistical differences in adipocytokine concentrations according to the different definitions of MHO, such as that including hs-CRP, because we did not have data on hs-CRP concentrations in the whole study population. We agree with Prof. Kim in that the results could have differed according to the different definitions of MHO. We also agree with Prof. Kim that a longitudinal study that includes both baseline and follow-up adipocytokine concentrations and the metabolic status of the participants would uncover the exact relationship between adipocytokines and metabolic health. Finally, we wish to thank the editorial board of EnM for their endless efforts in maintaining the prosperity of EnM and for giving us the chance to publish our work in their journal.

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          Most cited references6

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          Insulin-sensitive obesity.

          The association between obesity and impaired insulin sensitivity has long been recognized, although a subgroup of obese individuals seems to be protected from insulin resistance. In this study, we systematically studied differences in adipose tissue biology between insulin-sensitive (IS) and insulin-resistant (IR) individuals with morbid obesity. On the basis of glucose infusion rate during euglycemic hyperinsulinemic clamps, 60 individuals with a BMI of 45 +/- 1.3 kg/m(2) were divided into an IS and IR group matched for age, sex, and body fat prior to elective surgery. We measured fat distribution, circulating adipokines, and parameters of inflammation, glucose, and lipid metabolism and characterized adipose tissue morphology, function, and mRNA expression in abdominal subcutaneous (sc) and omental fat. IS compared with IR obese individuals have significantly lower visceral fat area (138 +/- 27 vs. 316 +/- 91 cm(2)), number of macrophages in omental adipose tissue (4.9 +/- 0.8 vs. 13.2 +/- 1.4%), mean omental adipocyte size (528 +/- 76 vs. 715 +/- 81 pl), circulating C-reactive protein, progranulin, chemerin, and retinol-binding protein-4 (all P values <0.05), and higher serum adiponectin (6.9 +/- 3.4 vs. 3.4 +/- 1.7 ng/ml) and omental adipocyte insulin sensitivity (all P values <0.01). The strongest predictors of insulin sensitivity by far were macrophage infiltration together with circulating adiponectin (r(2) = 0.98, P < 0.0001). In conclusion, independently of total body fat mass, increased visceral fat accumulation and adipose tissue dysfunction are associated with IR obesity. This suggests that mechanisms beyond a positive caloric balance such as inflammation and adipokine release determine the pathological metabolic consequences in patients with obesity.
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            Does inflammation determine metabolic health status in obese and nonobese adults?

            Inflammation is a potential mechanism linking obesity and cardiometabolic risk. Limited data on inflammatory markers in metabolically healthy obese and nonobese individuals exist. The aim of the study was to investigate the extent to which differences between metabolically healthy and unhealthy obese and nonobese adults, defined using a range of metabolic health definitions, are correlated with a range of inflammatory markers. A cross-sectional sample of 2047 men and women aged 45-74 years participated in the study. Participants were classified as obese (body mass index ≥ 30 kg/m(2)) and nonobese (body mass index < 30 kg/m(2)). Metabolic health status was defined using 5 existing metabolic health definitions based on a range of cardiometabolic abnormalities. Serum acute-phase reactants, adipocytokines, proinflammatory cytokines, and white blood cell counts were determined. According to most definitions, metabolically healthy obese and nonobese individuals presented with lower concentrations of complement component 3, C-reactive protein, TNF-α, IL-6, and plasminogen activator inhibitor-1; higher adiponectin levels; and reduced white blood cell count compared to their metabolically unhealthy counterparts. Logistic regression analysis identified greater likelihood of metabolically healthy obesity among individuals with lower levels of complement component 3 (odds ratios [ORs], 2-3.5), IL-6 (ORs, 1.7-2.9), plasminogen activator inhibitor-1 (ORs, 1.7-2.9), and white blood cells (ORs, 2.1-2.5) and higher adiponectin concentrations (ORs, 2.6-4.0). Favorable inflammatory status is positively associated with metabolic health in obese and nonobese individuals. These findings are of public health and clinical significance in terms of screening and stratification based on metabolic health phenotype to identify those at greatest cardiometabolic risk for whom appropriate therapeutic or intervention strategies should be developed.
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              Metabolically healthy obesity: different prevalences using different criteria.

              To estimate the prevalence of metabolically healthy obesity (MHO) according to different definitions. Population-based sample of 2803 women and 2557 men participated in the study. Metabolic abnormalities were defined using six sets of criteria, which included different combinations of the following: waist; blood pressure; total, high-density lipoprotein or low-density lipoprotein-cholesterol; triglycerides; fasting glucose; homeostasis model assessment; high-sensitivity C-reactive protein; personal history of cardiovascular, respiratory or metabolic diseases. For each set, prevalence of MHO was assessed for body mass index (BMI); waist or percent body fat. Among obese (BMI 30 kg/m(2)) participants, prevalence of MHO ranged between 3.3 and 32.1% in men and between 11.4 and 43.3% in women according to the criteria used. Using abdominal obesity, prevalence of MHO ranged between 5.7 and 36.7% (men) and 12.2 and 57.5% (women). Using percent body fat led to a prevalence of MHO ranging between 6.4 and 43.1% (men) and 12.0 and 55.5% (women). MHO participants had a lower odd of presenting a family history of type 2 diabetes. After multivariate adjustment, the odds of presenting with MHO decreased with increasing age, whereas no relationship was found with gender, alcohol consumption or tobacco smoking using most sets of criteria. Physical activity was positively related, whereas increased waist was negatively related with BMI-defined MHO. MHO prevalence varies considerably according to the criteria used, underscoring the need for a standard definition of this metabolic entity. Physical activity increases the likelihood of presenting with MHO, and MHO is associated with a lower prevalence of family history of type 2 diabetes.
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                Author and article information

                Journal
                Endocrinol Metab (Seoul)
                Endocrinol Metab (Seoul)
                ENM
                Endocrinology and Metabolism
                Korean Endocrine Society
                2093-596X
                2093-5978
                September 2015
                22 September 2015
                : 30
                : 3
                : 416-417
                Affiliations
                Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Eun-Jung Rhee. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea. Tel: +82-2-2001-2485, Fax: +82-2-2001-1588, hongsiri@ 123456hanmail.net
                Article
                10.3803/EnM.2015.30.3.416
                4595370
                26435139
                2cdee357-0f39-41e2-b9a4-8fec856ff4cd
                Copyright © 2015 Korean Endocrine Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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