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Adipose tissue morphology, imaging and metabolomics predicting cardiometabolic risk and family history of type 2 diabetes in non-obese men.

ABSTRACT: We evaluated the importance of body composition, amount of subcutaneous and visceral fat, liver and heart ectopic fat, adipose tissue distribution and cell size as predictors of cardio-metabolic risk in 53 non-obese male individuals. Known family history of type 2 diabetes was identified in 25 individuals. The participants also underwent extensive phenotyping together with measuring different biomarkers and non-targeted serum metabolomics. We used ensemble learning and other machine learning approaches to identify predictors with considerable relative importance and their intricate interactions. Visceral fat and age were strong individual predictors of ectopic fat accumulation in liver and heart along with markers of lipid oxidation and reduced glucose tolerance. Subcutaneous adipose cell size was the strongest individual predictor of whole-body insulin sensitivity and also a marker of visceral and ectopic fat accumulation. The metabolite 3-MOB along with related branched-chain amino acids demonstrated strong predictability for family history of type 2 diabetes.

SUBMITTER: Rawshani A

PROVIDER: S-EPMC7305301 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Adipose tissue morphology, imaging and metabolomics predicting cardiometabolic risk and family history of type 2 diabetes in non-obese men.

Rawshani Aidin A Eliasson Björn B Rawshani Araz A Henninger Josefin J Mardinoglu Adil A Carlsson Åsa Å Sohlin Maja M Ljungberg Maria M Hammarstedt Ann A Rosengren Annika A Smith Ulf U

Scientific reports 20200619 1

We evaluated the importance of body composition, amount of subcutaneous and visceral fat, liver and heart ectopic fat, adipose tissue distribution and cell size as predictors of cardio-metabolic risk in 53 non-obese male individuals. Known family history of type 2 diabetes was identified in 25 individuals. The participants also underwent extensive phenotyping together with measuring different biomarkers and non-targeted serum metabolomics. We used ensemble learning and other machine learning app ...[more]

PMID: 32561768

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Project description:AimObesity is linked to cardiometabolic diseases, however non-obese individuals are also at risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). White adipose tissue (WAT) is known to play a role in both T2D and CVD, but the contribution of WAT inflammatory status especially in non-obese patients with cardiometabolic diseases is less understood. Therefore, we aimed to find associations between WAT inflammatory status and cardiometabolic diseases in non-obese individuals.MethodsIn a population-based cohort containing non-obese healthy (n = 17), T2D (n = 16), CVD (n = 18), T2D + CVD (n = 19) individuals, seventeen different cytokines were measured in WAT and in circulation. In addition, 13-color flow cytometry profiling was employed to phenotype the immune cells. Human T cell line (Jurkat T cells) was stimulated by rCCL18, and conditioned media (CM) was added to the in vitro cultures of human adipocytes. Lipolysis was measured by glycerol release. Blocking antibodies against IFN-γ and TGF-β were used in vitro to prove a role for these cytokines in CCL18-T-cell-adipocyte lipolysis regulation axis.ResultsIn CVD, T2D and CVD + T2D groups, CCL18 and CD4+ T cells were upregulated significantly compared to healthy controls. WAT CCL18 secretion correlated with the amounts of WAT CD4+ T cells, which also highly expressed CCL18 receptors suggesting that WAT CD4+ T cells are responders to this chemokine. While direct addition of rCCL18 to mature adipocytes did not alter the adipocyte lipolysis, CM from CCL18-treated T cells increased glycerol release in in vitro cultures of adipocytes. IFN-γ and TGF-β secretion was significantly induced in CM obtained from T cells treated with CCL18. Blocking these cytokines in CM, prevented CM-induced upregulation of adipocyte lipolysis.ConclusionWe suggest that in T2D and CVD, increased production of CCL18 recruits and activates CD4+ T cells to secrete IFN-γ and TGF-β. This, in turn, promotes adipocyte lipolysis - a possible risk factor for cardiometabolic diseases.

Dataset Information

Adipose tissue morphology, imaging and metabolomics predicting cardiometabolic risk and family history of type 2 diabetes in non-obese men.

Publications

Adipose tissue morphology, imaging and metabolomics predicting cardiometabolic risk and family history of type 2 diabetes in non-obese men.

Similar Datasets

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