Propionate Induces Energy Expenditure via Browning in Mesenteric Adipose Tissue

Abstract

Context: Short-chain fatty acids, such as propionate, are produced from the fermentation of dietary fiber by gut microbiota and modulate adipose tissue (AT) metabolism to influence whole-body metabolic processes. Abdominal AT, critical in glucose and lipid homeostasis, is categorized into mesenteric, omental, and subcutaneous types based on its location. ATs display different metabolic phenotypes due to their distinct adipocyte lineages—white, brown, and beige. Recent evidence points to a significant effect of propionate on abdominal AT. Objective: Our study investigated the actions of propionate on the 3 types of human abdominal AT. Methods: AT from distinct depots (mesenteric, omental, and subcutaneous) were collected from 40 patients who underwent open abdominal surgery for cholecystectomy or explorative laparotomy. Tissue explants and isolated adipocytes were treated with 1 mM propionate to assess AT browning and metabolic homeostasis. Results: Propionate upregulated brown fat markers UCP1 and PGC1α in adipose tissue and mature adipocytes, particularly of mesenteric origin. Propionate exposure led to increased mitochondrial respiration and adenosine triphosphate production, primarily in mesenteric adipocytes, along with improved glucose uptake and reduced lipolysis and inflammation. In addition, propionate increased thermogenesis, glycolysis, and lipogenesis. Conclusion: The pronounced response of mesenteric AT to propionate underscores its potential as a therapeutic target for managing abdominal obesity and metabolic disorders.