Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy

Abstract

OBJECTIVEIt has been suggested that individuals with the condition known as metabolically healthy obesity (MHO) may not have the same increased risk for the development of metabolic abnormalities as their non-metabolically healthy counterparts. However, the validity of this concept has recently been challenged, since it may not translate into lower morbidity and mortality. The aim of the current study was to compare the cardiometabolic/inflammatory profile and the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) in patients categorized as having MHO or metabolically abnormal obesity (MAO). RESEARCH DESIGN AND METHODSWe performed a cross-sectional analysis to compare the cardiometabolic/inflammatory profile of 222 MHO and 222 MAO patients (62% women) matched by age, including 255 lean subjects as reference (cohort 1). In a second cohort, we analyzed the adipokine profile and the expression of genes involved in inflammation and extracellular matrix remodeling in visceral adipose tissue (VAT; n = 82) and liver (n = 55). RESULTSThe cardiometabolic and inflammatory profiles (CRP, fibrinogen, uric acid, leukocyte count, and hepatic enzymes) were similarly increased in MHO and MAO in both cohorts. Moreover, above 30% of patients classified as MHO according to fasting plasma glucose exhibited IGT or T2D. The profile of classic (leptin, adiponectin, resistin) as well as novel (serum amyloid A and matrix metallopeptidase 9) adipokines was almost identical in MHO and MAO groups in cohort 2. Expression of genes involved in inflammation and tissue remodeling in VAT and liver showed a similar alteration pattern in MHO and MAO individuals. CONCLUSIONSThe current study provides evidence for the existence of a comparable adverse cardiometabolic profile in MHO and MAO patients; thus the MHO concept should be applied with caution. A better identification of the obesity phenotypes and a more precise diagnosis are needed for improving the management of obese individuals.

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin, chitinase-3-like protein 1, lipocalin-2 and osteopontin

“…In agreement with our findings, no differences in the expression of inflammatory genes in adipose tissue or PBMC between metabolically obese healthy and metabolically abnormal obesity groups have been found in recent studies (Catalán et al 2007a;Gómez-Ambrosi et al 2014;Telle-Hansen et al 2013). Moreover, we have identified that the upregulation of gene expression levels of most of the novel adipokines in PBMC is associated with their circulating concentrations, suggesting the contribution of these types of cells to the increased circulating levels in obesity states.…”

Does metabolic health in overweight and obesity persist? – Individual variation and cardiovascular mortality over two decades

“…The second hypothesis was that MH OWOB individuals are insulin resistant and exhibit sub-clinical inflammation relative to MH NW individuals. This was the case and, with regard to inflammation, accords with a previous report of increased inflammation in MHO individuals (27). This could suggest that further discrimination of MH among OWOB individuals may be possible using measures of insulin resistance and sub-clinical inflammation.…”

Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease

“…Adipocyte-derived hormones and cytokines including leptin, adiponectin, interleukin-6, and tumor necrosis factor-alpha may be involved in the pathogenesis of NAFLD ( 7 ). Indeed, the expression of infl ammatory genes was similarly altered in both MHO and metabolically unhealthy obese subjects, highlighting that MHO individuals may exhibit an adverse profi le comparable with that of metabolically unhealthy obese patients and that the MHO concept should be applied with caution ( 35 ). Finally, recent studies suggest that the MHO phenotype is transient and progresses to overt metabolic abnormalities in a signifi cant proportion of individuals ( 36,37 ), although the association between BMI and incident NAFLD in our study was evident across all BMI levels and was not restricted to MHO participants.…”