Dataset Information

Untargeted Metabolomic Approach Shows No Differences in Subcutaneous Adipose Tissue of Diabetic and Non-Diabetic Subjects Undergoing Bariatric Surgery: An Exploratory Study.

ABSTRACT:

Background

Obesity plays a major role in the development of insulin resistance (IR) and diabetes (T2DM). Increased adipose tissue (AT) is particularly of interest because it activates a chronic inflammatory response in adipocytes and other tissues. AT plays key endocrine and metabolic functions, acting in the regulation of insulin sensitivity and energy homeostasis. Additionally, it can be easily collected during bariatric surgery. The purpose of this pilot study was to explore the potential differences in AT metabolism, through comparing the untargeted metabolomic profiles of diabetic and non-diabetic obese patients undergoing bariatric surgery.

Methods

For this exploratory study, samples were collected from 17 subjects. Subcutaneous AT (SAT) samples from obese-diabetic (n = 8) and Obese-non-Diabetic (n = 9) subjects were obtained from the Human Metabolic Tissue Bank. Untargeted metabolomic profiling was performed by Metabolon® Inc. Statistical analysis was performed using the MetaboAnalyst 4.0 platform.

Results

Among the 421 metabolites identified and analyzed there were no significant differences between the Obese-Diabetics and the Obese-non-Diabetics. Small changes were observed by fold change analysis mainly in lipid (n = 12; e.g. NEFAs) and amino acid (n = 8; e.g. BCAAs) metabolic pathways. Dysregulation of these metabolites has been associated with IR and other T2DM-related pathophysiological processes.

Conclusion

Obesity may influence SAT metabolism masking T2DM-dependent dysregulation. Better understanding the metabolic differences within SAT in diabetic populations may help identify potential biomarkers for diagnosis and monitoring of T2DM in patients undergoing bariatric surgery.

SUBMITTER: Vizioli C

PROVIDER: S-EPMC7874365 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.MethodsWe aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB.ResultsAnalysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all).ConclusionsOur findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB. Trial registration CAAE: 73,585,317.0.0000.5440.