Dysglycemia Shapes Visceral Adipose Tissue’s Response to GIP, GLP-1 and Glucagon in Individuals with Obesity

Abstract

Visceral adipose tissue (VAT) metabolic fingerprints differ according to body mass index (BMI) and glycemic status. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon are gut-associated hormones that play an important role in regulating energy and glucose homeostasis, although their metabolic actions in VAT are still poorly characterized. Our aim was to assess whether GLP-1, GIP and glucagon influence the VAT metabolite profile. To achieve this goal, VAT harvested during elective surgical procedures from individuals (N = 19) with different BMIs and glycemic statuses was stimulated with GLP-1, GIP or glucagon, and culture media was analyzed using proton nuclear magnetic resonance. In the VAT of individuals with obesity and prediabetes, GLP-1 shifted its metabolic profile by increasing alanine and lactate production while also decreasing isoleucine consumption, whereas GIP and glucagon decreased lactate and alanine production and increased pyruvate consumption. In summary, GLP-1, GIP and glucagon were shown to distinctively modulate the VAT metabolic profile depending on the subject’s BMI and glycemic status. In VAT from patients with obesity and prediabetes, these hormones induced metabolic shifts toward gluconeogenesis suppression and oxidative phosphorylation enhancement, suggesting an overall improvement in AT mitochondrial function.

Keywords

• adipose tissue
• metabolomics
• obesity
• insulin resistance
• GlP-1
• GIP