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'Metabolically healthy obesity': origins and implications.

ABSTRACT: When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mechanisms behind this conundrum: individuals who exhibit metabolic dysfunction, diabetes and elevated cardiovascular disease risk despite a lean body type, and individuals who are relatively protected from these dangers despite significant obesity. Study of this second group of 'metabolically healthy obese' people in particular has been revealing because such individuals exhibit specific, identifiable, anatomic, cellular and molecular features that set them apart from the rest of us who suffer declining health with increasing weight. Here, we examine some of these features, including some mouse models that are informative of mechanism, and suggest hypotheses for further study, including the possibility that genes and pathways of the immune system might offer new diagnostic or therapeutic targets.

SUBMITTER: Denis GV

PROVIDER: S-EPMC3583231 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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'Metabolically healthy obesity': origins and implications.

Denis Gerald V GV Obin Martin S MS

Molecular aspects of medicine 20121013 1

When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mecha ...[more]

PMID: 23068072

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Project description:ObjectivesTo analyze sex differences in the prevalence of obesity phenotypes and their risk factors among children and adolescents aged 7-18 years in China.MethodsWe enrolled 15,114 children and adolescents aged 7-18 years into the final analysis. Obesity phenotypes were classified by body mass index (BMI) and metabolic status as metabolically healthy or unhealthy obesity. In addition, we collected four possible influencing factors on obesity phenotypes through questionnaires, including demographic, parental, early life, and lifestyle indicators. Multinomial logistic regression analysis in a generalized linear mixed model (GLMM) was selected to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for identifying risk factors and control the cluster effects of schools. More importantly, the interaction terms of sex and each indicator were established to demonstrate the sex differences.ResultsThe prevalence of metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy overweight and obesity (MHOO), and metabolically unhealthy overweight and obesity (MUOO) were 3.5%, 5.6%, 11.1%, and 13.0% respectively, with higher prevalence in boys (5.3% vs. 1.6%, 7.9% vs. 3.1%, 14.3% vs. 7.7%, 15.6% vs. 10.1%). In addition, younger ages, single children, parental smoking, parental history of diseases (overweight, hypertension, diabetes), caesarean, premature, and delayed delivery time, high birth weight, insufficient sleep time, and excessive screen time were considered as important risk factors of MHO and MUO among children and adolescents (p < 0.05). More notably, boys were at higher risks of MUO when they were single children (boys: OR = 1.56, 95% CI: 1.24-1.96; girls: OR = 1.12, 95% CI: 0.82-1.54), while girls were more sensitive to MUO with parental smoking (girls: OR = 1.34, 95% CI: 1.02-1.76; boys: OR = 1.16, 95% CI: 0.97-1.39), premature delivery (girls: OR = 3.11, 95% CI: 1.59-6.07; boys: OR = 1.22, 95% CI: 0.67-2.22), high birth weight (girls: OR = 2.45, 95% CI: 1.63-3.69; boys: OR = 1.28, 95% CI: 0.96-1.70), and excessive screen time (girls: OR = 1.47, 95% CI: 1.06-2.04; boys: OR = 0.97, 95% CI: 0.79-1.20), with significant interaction term for sex difference (pinteraction < 0.05).ConclusionsMHO and MUO are becoming prevalent among Chinese children and adolescents. Significant sex differences in the prevalence of obesity phenotypes as well as their environmental and genetic risk factors suggest it might be necessary to manage obesity phenotypes problems from a sex perspective.

Project description:The risk of colorectal adenoma (CRA), an important precursor of colorectal cancer, is largely unknown among obese individuals without obesity-related metabolic abnormalities, a condition described as metabolically-healthy obese (MHO). The aim of this study was to examine the association among metabolic status, the different categories of body mass index (BMI), and CRA in a large cohort of adults.We analyzed the association among metabolic status, BMI categories and CRA in asymptomatic adults who underwent a first-time colonoscopy as part of the comprehensive health check-up program at the Health Promotion Center of Samsung Medical Center, from January 2005 to December 2012. Being metabolically healthy was defined as lacking any metabolic syndrome components and having a homeostasis model assessment of insulin resistance <2.5.The prevalence of "any," "multiple," and "high-risk" CRA was 25.6%, 8.3%, and 4.4% among 9,182 metabolically-healthy participants, and 35.9%, 12.5%, and 7.0% among 17,407 metabolically-unhealthy participants, respectively. Increased BMI showed a significant dose-dependent relationship with the prevalence of "any," "multiple," and "high-risk" CRA, in both metabolically-healthy and unhealthy participants. In multivariable-adjusted models that accounted for potential confounders including age, sex, smoking, alcohol, first-degree family history of colorectal cancer, and aspirin use, the odds ratio (OR) for any CRA comparing MHO with metabolically-healthy normal-weight (MHNW) participants was 1.25 (95% confidence interval (CI), 1.09-1.43). Further adjustment for metabolic components associated with obesity did not significantly change the association. Similarly, the ORs for multiple CRAs and high risk CRA were higher in MHO participants than MHNW participants [ORs (95% CI), 1.63 (1.31-2.04) and 1.53 (1.14-2.04), respectively].The MHO phenotype was closely associated with higher prevalence of CRA, including high-risk adenoma. This finding supports the conclusion that MHO increases the risk of colorectal cancer.

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'Metabolically healthy obesity': origins and implications.

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'Metabolically healthy obesity': origins and implications.

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