Abstract
Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (1H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals’ health status.
Highlights
IntroductionAdipose tissue (AT) maladaptation is believed to lead to obesity-related metabolic disorders such as insulin resistance (IR), pre-diabetes and type 2 diabetes (T2D) [2]
We performed a comprehensive evaluation of Adipose tissue (AT) metabolomics, by qualitatively and quantitatively analyzing the extracellular metabolite shifts of ex-vivo Visceral adipose tissue (VAT)
In the presence of similar insulin concentrations, there are no significant differences in glucose consumption within the VAT across different study groups, further suggesting that impaired glucose uptake is not a prominent VAT feature despite the systemic phenotype, as previously highlighted [14,15]
Summary
Adipose tissue (AT) maladaptation is believed to lead to obesity-related metabolic disorders such as insulin resistance (IR), pre-diabetes and T2D [2]. These conditions are characterized by a full spectrum of systemic imbalances that culminate in the disruption of glucose homeostasis [3]. Processes underlying pre-diabetes and T2D are a continuum that is initiated by resistance to insulin action in mediating glucose transport in peripheral organs, such as the liver, skeletal muscle and AT [4]. Whenever the pancreatic capacity to sustain insulin hypersecretion is overridden, circulating glucose levels increase and pre-diabetes or overt T2D occurs [4]. Hampered insulin signaling impairs the suppression of gluconeogenesis and overall mitochondrial function [5,6]
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