Minireviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Aug 26, 2015; 6(3): 223-230
Published online Aug 26, 2015. doi: 10.4331/wjbc.v6.i3.223
Essential roles of four-carbon backbone chemicals in the control of metabolism
Sabrina Chriett, Luciano Pirola
Sabrina Chriett, Luciano Pirola, INSERM Unit 1060, South Lyon Hospital, Medical Faculty, CarMeN Laboratory, Lyon-1 University, INRA U1397, 69921 Oullins, France
Author contributions: Both authors contributed equally to this manuscript.
Conflict-of-interest statement: Neither of the authors have conflicts of interest related to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Luciano Pirola, INSERM Unit 1060, South Lyon Hospital, Medical Faculty, CarMeN Laboratory, Lyon-1 University, INRA U1397, 165 Ch. du Grand Revoyet - BP12, 69921 Oullins, France. luciano.pirola@univ-lyon1.fr
Telephone: +33-4-26235948
Received: January 28, 2015
Peer-review started: February 1, 2015
First decision: March 20, 2015
Revised: May 11, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: August 26, 2015
Abstract

The increasing incidence of obesity worldwide and its related cardiometabolic complications is an urgent public health problem. While weight gain results from a negative balance between the energy expenditure and calorie intake, recent research has demonstrated that several small organic molecules containing a four-carbon backbone can modulate this balance by favoring energy expenditure, and alleviating endoplasmic reticulum stress and oxidative stress. Such small molecules include the bacterially produced short chain fatty acid butyric acid, its chemically produced derivative 4-phenylbutyric acid, the main ketone body D-β-hydroxybutyrate - synthesized by the liver - and the recently discovered myokine β-aminoisobutyric acid. Conversely, another butyrate-related molecule, α-hydroxybutyrate, has been found to be an early predictor of insulin resistance and glucose intolerance. In this minireview, we summarize recent advances in the understanding of the mechanism of action of these molecules, and discuss their use as therapeutics to improve metabolic homeostasis or their detection as early biomarkers of incipient insulin resistance.

Keywords: Butyric acid, D-β-hydroxybutyrate, Histone deacetylases, Histone deacetylases inhibitors, Insulin resistance

Core tip: Recent research demonstrated that the four-carbon molecule butyrate, and butyrate-related molecules (4-phenylbutyric acid, D-β-hydroxybutyrate and β-aminoisobutyric acid), act as modulators of metabolism, favoring energy expenditure. Conversely, another butyrate-related molecule, α-hydroxybutyrate, is an early predictor of insulin resistance and glucose intolerance. In this minireview, we summarize the recent progress in the understanding of the mechanism of action of these molecules and discuss their possible therapeutic use to improve metabolic homeostasis and their usefulness as early biomarkers for insulin resistance.