Endocrine Abstracts

Visceral adipose tissue (VAT) metabolic fingerprints differ according to the individual’s BMI and glycemic status. GLP-1 and Glucagon are two hormones that participate in energy homeostasis and glycemic control. Dual GLP-1/Glucagon agonists are a drug class under development for obesity and diabetes treatment. Although the pancreas and the liver are considered major GLP-1 and glucagon targets, these hormones act in other tissues, which could contribute for its effects on glucose balance. Thus, our purpose was to assess how GLP-1 and Glucagon influence VAT metabolic fingerprints according to the individual’s BMI and glycemic status. Subjects (n=19) undergoing elective abdominal surgery for non-infectious nor oncologic conditions were included in this study. Subjects were allocated into 4 experimental groups according to BMI and glycemic status, namely with obesity and euglycemia (Ob+NGT, n=5), obesity and pre-diabetes (Ob+Pre-T2D, n=5), obesity and T2D (Ob+T2D, n=5). Subjects without obesity or dysglycemia were used as controls (Non-Ob, n=4). VAT harvested during the surgical procedure was kept in culture media supplemented with insulin (100 nM) and exposed for 48 h to GLP-1 or glucagon at different concentrations (1, 10 or 100 nM). Culture media was then collected for proton nuclear magnetic resonance (¹ H-NMR) analysis. In VAT of Non-Ob controls, GLP-1 decreased acetate production (-25.20 %, P<0.05), while in Ob+NGT glucagon increased valine consumption (76.6%, P<0.05). In VAT of subjects with Ob + Pre-T2D, GLP-1 decreased isoleucine consumption (-99.6%, P<0.05), but increased alanine (32.6%, P<0.05) and lactate (43.8%, P<0.01) production. Glucagon decreased the consumption of isoleucine (-55.2%, P<0.05) and valine (-169.2%, P<0.01), as well as the production of alanine (-28.0%, P<0.05) and lactate (-54.4%, P<0.05), while increasing pyruvate consumption (10.9%, P<0.05). VAT of Ob+T2D subjects depicted no changes in metabolite profile after exposure to GLP-1 or glucagon. GLP-1 and glucagon are able to modify VAT metabolic profile, particularly in obesity and pre-diabetes. GLP-1 shifts VAT metabolic profile by decreasing isoleucine consumption and increasing alanine/lactate production, which suggests decreased gluconeogenesis. Glucagon lowers isoleucine and valine consumption, coupled with the decrease in lactate and alanine production, whilst increases pyruvate consumption, which suggests an increase in oxidative phosphorylation. Overall, out data suggests that dual GLP-1/Glucagon agonists’ action in VAT could also play a role in mediating its glucose lowering and catabolic effects.

Funding: Fundação para a Ciência e Tecnologia (FCT), Portugal (PTDC/MECMET/32151/2017, UIDB/00215/2020 and UIDP/00215/2020). T. Morais funded by FCT (SFRH/BD/123437/2016).