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Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity.

ABSTRACT: The prevalence of obesity and obesity-related metabolic comorbidities are rapidly increasing worldwide, placing a huge economic burden on health systems. Excessive nutrient supply combined with reduced physical exercise results in positive energy balance that promotes adipose tissue expansion. However, the metabolic response and pattern of fat accumulation is variable, depending on the individual's genetic and acquired susceptibility factors. Some develop metabolically healthy obesity (MHO) and are resistant to obesity-associated metabolic diseases for some time, whereas others readily develop metabolically unhealthy obesity (MUO). An unhealthy response to excess fat accumulation could be due to susceptibility intrinsic factors (e.g., increased likelihood of dedifferentiation and/or inflammation), or by pathogenic drivers extrinsic to the adipose tissue (e.g., hyperinsulinemia), or a combination of both. This review outlines the major transcriptional factors and genes associated with adipogenesis and regulation of adipose tissue homeostasis and describes which of these are disrupted in MUO compared to MHO individuals. It also examines the potential role of pathogenic insulin hypersecretion as an extrinsic factor capable of driving the changes in adipose tissue which cause transition from MHO to MUO. On this basis, therapeutic approaches currently available and emerging to prevent and reverse the transition from MHO to MUO transition are reviewed.

SUBMITTER: Dagpo TD

PROVIDER: S-EPMC7407965 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity.

Dagpo Tenzin D TD Nolan Christopher J CJ Delghingaro-Augusto Viviane V

Cells 20200701 7

The prevalence of obesity and obesity-related metabolic comorbidities are rapidly increasing worldwide, placing a huge economic burden on health systems. Excessive nutrient supply combined with reduced physical exercise results in positive energy balance that promotes adipose tissue expansion. However, the metabolic response and pattern of fat accumulation is variable, depending on the individual's genetic and acquired susceptibility factors. Some develop metabolically healthy obesity (MHO) and ...[more]

PMID: 32630256

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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:BackgroundMetabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories.Methods and findingsThe China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification.ConclusionsAmong Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.

Dataset Information

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity.

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Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity.

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