Intraperitoneal Administration of Short-Chain Fatty Acids Improves Lipid Metabolism of Long-Evans Rats in a Sex-Specific Manner.

Raymond Thomas,Shrushti Shah,Thu Huong Pham,Sukhinder Kaur Cheema,Tiffany Fillier

doi:10.3390/nu13030892

Raymond Thomas, Shrushti Shah + Show 3 more

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https://doi.org/10.3390/nu13030892

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Journal: Nutrients	Publication Date: Mar 10, 2021
Citations: 14	License type: CC BY 4.0

Affiliation: Memorial University of Newfoundland

Abstract

Short-chain fatty acids (SCFAs) are microbial metabolites, mainly generated by the action of gut microbiota on dietary fibers. Acetate, propionate, and butyrate are the three main SCFAs produced typically in a 60:20:20 molar ratio in the colon. Acetate, propionate, and butyrate, when given individually as supplements, have shown a protective role in obesity and hyperglycemia; however, the sex-specific effects of a mixture of SCFAs, when given in 60:20:20 ratio, on the regulation of lipid metabolism and lipid profile are not known. Male and female Long–Evans rats were given a mixture of SCFAs (acetate, propionate, and butyrate; molar ratio 60:20:20) each day for seven days intraperitoneally; plasma and hepatic lipids, gene expression, and lipidomics profile were analyzed. SCFAs significantly decreased plasma and hepatic triglycerides and cholesterol in males, whereas the fatty acyl composition of cholesteryl esters, triglycerides, and phospholipids was modulated in females. SCFAs decreased the mRNA expression of hepatic acetyl-CoA carboxylase-1 in both males and females. Our findings demonstrate for the first time that SCFAs (60:20:20) improved plasma and hepatic lipid levels and fatty acyl composition in a manner that may provide cardio-protective and anti-inflammatory effects in both sexes, via independent mechanisms.

Highlights

Published: 10 March 2021Gut-microbiota and their metabolites have recently gained much interest in the scientific community due to their roles in the regulation of lipids and glucose metabolism [1,2].The digestion of dietary fibers and other complex carbohydrates by gut microbiota produces short-chain fatty acids (SCFAs) as one of its many metabolites
Since acetate is incorporated into longer-chain fatty acids (LCFAs), which are used to form complex lipids [5], we investigated the effects of SCFAs on the plasma and hepatic lipidomics profile
It would be interesting to look into hepatic phosphatidylethanolamine N-methyltransferase (Pemt) and other enzymes involved in PUFA synthesis in the future because our results show that SCFAs increased incorporation of n-3 PUFAs irrespective of 16:0 or 18:0 at the sn1 position of the glycerol moiety in PC

Summary

Introduction

Published: 10 March 2021Gut-microbiota and their metabolites have recently gained much interest in the scientific community due to their roles in the regulation of lipids and glucose metabolism [1,2].The digestion of dietary fibers and other complex carbohydrates by gut microbiota produces short-chain fatty acids (SCFAs) as one of its many metabolites. Once produced in the gut, acetate and propionate are mainly taken up by the liver from portal circulation, where these act as a substrate for de novo synthesis of longer-chain fatty acids (LCFAs), and hepatic gluconeogenesis, respectively [4,5]. Much of the biochemistry of SCFAs is known, accurate production rates of acetate, propionate, and butyrate in humans are not conclusive [7]. This is because of the inadequate data from human intestinal samples and the variability of the microbiome in healthy individuals [5]. Rodent [8] and swine [9] models have indicated that the molar ratio of acetate:propionate:butyrate produced in the colon is approximately 60:20:20; human

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