Propionic acid counteracts the inflammation of human subcutaneous adipose tissue: a new avenue for drug development.

Abstract

Adipose tissue is a primary site of obesity-induced inflammation, which has been emerging as an important contributor to obesity associated disorders. The factors influencing adipose tissue-induced inflammation and the resulting pathophysiological events remain poorly understood. However, dietary fiber consumptions appear to be protective. Short-chain fatty acids such as propionic acid (PA) are the principal products of the dietary fiber fermentation by microbiota. Therefore, we aim to investigate the influence of PA on inflammation, lipogenesis and glucose uptake markers from human subcutaneous adipose tissue (SAT). We showed that the treatment of SAT with PA resulted in a significant downregulation of inflammatory parameters (e.g. TNF-α and IP-10) and macrophage markers (e.g. CD163 and MMP-9). The expression levels of PA receptors (i.e. G protein coupled receptor-41 and -43) in human primary adipocytes were very low in comparison with SAT and macrophages. Upon PA treatment, no anti-inflammatory effect was observed in human adipocytes. PA significantly upregulated the expression of lipoprotein lipase (LPL), sterol regulatory-element-binding protein-1c (SREBP-1c) and glucose transporter 4 (GLUT-4), which are associated with lipogenesis and glucose uptake. We also showed that the observed anti-inflammatory effects of PA on SAT were partly mediated by Gi/o protein coupled receptor. Our data suggests that PA anti-inflammatory effects on SAT are mediated partly via Gi/o proteins, leading to the improved expression of factors associated with lipogenesis and glucose uptake. These responses appeared to be not mediated by adipocytes; but most probably by macrophages. The current study provides new knowledge, which can be used as a potential new avenue for drug development in preventing obesity-related inflammation and metabolic disorders in future. Graphical abstract Schematic presentation of study flow and the components of the investigation. In this study the effect of propionic acid (PA) on inflammation investigated in human subcutaneous adipose tissue (SAT), human primary adipocytes and the expression of a few hallmark inflammatory components produced by SAT and human adipocytes.

• Authors: Sa'ad Al-Lahham, Farhad Rezaee
• Journal: Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences (Daru) Vol. 27 Issue 2 Pg. 645-652 (Dec 2019) ISSN: 2008-2231 [Electronic] Switzerland
• PMID: 31512194 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD163 antigen
• CXCL10 protein, human
• Chemokine CXCL10
• Cytokines
• Propionates
• Receptors, Cell Surface
• TNF protein, human
• Tumor Necrosis Factor-alpha
• MMP9 protein, human
• Matrix Metalloproteinase 9
• GTP-Binding Protein alpha Subunits, Gi-Go
• propionic acid

Topics

• Anti-Inflammatory Agents (pharmacology)
• Antigens, CD (genetics)
• Antigens, Differentiation, Myelomonocytic (genetics)
• Chemokine CXCL10 (genetics)
• Cytokines (genetics)
• Down-Regulation
• Female
• GTP-Binding Protein alpha Subunits, Gi-Go (genetics)
• Gene Expression Regulation (drug effects)
• Humans
• Matrix Metalloproteinase 9 (genetics)
• Middle Aged
• Propionates (pharmacology)
• Receptors, Cell Surface (genetics)
• Subcutaneous Fat (drug effects, immunology)
• Tumor Necrosis Factor-alpha (genetics)