Title : Impact of the short chain fatty acid propionate on abdominal adipose tissue metabolism
Abstract:
Background and Aim: Adipose tissue, comprising white, brown, and beige depots, plays a central role in energy regulation. White adipose tissue (WAT) serves as an energy reservoir, while brown and beige adipose tissues are involved in thermogenesis, contributing to energy expenditure and metabolic health. Visceral adipose tissues, including mesenteric and omental depots, have a more significant impact on metabolic processes compared to subcutaneous fat. Propionate, a short-chain fatty acid produced by gut microbiota, has been shown to influence adipose tissue metabolism; however, its specific effects on distinct abdominal adipose depots remain unclear. This study investigates the role of propionate in modulating adipose tissue function, hypothesizing that it reduces adipocyte hypertrophy, promotes preadipocyte differentiation, and enhances metabolic functions across various adipose tissue types.
Methods: Adipose tissues from mesenteric, omental, and subcutaneous depots were collected from 40 patients undergoing elective surgery. The isolated adipose tissues and adipocytes were treated with 1 mM propionate or 1 mM NaCl (control) for 24 hours. Additionally, isolated preadipocytes were cultured for 14 days with either propionate or control to assess differentiation. Key metabolic and gene expression markers were analyzed in tissues, adipocytes, and preadipocytes to evaluate the impact of propionate on adipose function.
Results: Propionate exerts its effects primarily via the FFAR2 receptor. In mesenteric adipose tissue, it significantly upregulates browning markers such as UCP1 and PGC1α, while enhancing mitochondrial respiration and ATP production. In adipocytes, propionate elevates UCP1 expression, increases glucose uptake via enhanced GLUT4 expression, promotes glycolysis, and reduces lipolysis and inflammation. In preadipocytes, propionate stimulates adipogenic differentiation, enhances thermogenic gene expression, and improves mitochondrial function, leading to a reduction in glycerol release, particularly in mesenteric preadipocytes.
Discussion: Activation of FFAR2 by propionate leads to beneficial alterations in adipose tissue function, including enhanced thermogenesis, glycolysis, and lipogenesis, along with reduced inflammation and improved angiogenesis. These effects are most pronounced in mesenteric adipose tissue, suggesting that propionate may be a promising therapeutic candidate for addressing abdominal obesity and associated metabolic disorders. Furthermore, propionate significantly promotes adipogenesis by upregulating key adipogenic markers and inducing browning in preadipocytes, enhancing energy expenditure and ATP production during differentiation. These findings highlight propionate’s potential as a therapeutic agent to enhance metabolic activity in abdominal adipose depots and improve overall metabolic health.
