TY - JOUR
T1 - Etifoxine reverses weight gain and alters the colonic bacterial community in a mouse model of obesity
AU - Ibrahim, Khalid S.
AU - Craft, John A.
AU - Biswas, Lincoln
AU - Spencer, Janice
AU - Shu, Xinhua
N1 - Acceptance from webpage
^Chaser sent re file query including all GCU authors - can we log existing as AAM or is there another version. ET 14/8/20
PY - 2020/10
Y1 - 2020/10
N2 - Obesity is intimately associated with diet and dysbiosis of gut microorganisms but anxiolytics, widely used in treatment of psychiatric conditions, frequently result in weight gain and associated metabolic disorders. We are interested in effects of the anxiolytic Etifoxine, which has not been studied with respect to weight gain or effects on gut microorganisms. Here we induced obesity in mice by feeding a high-fat diet but found that intraperitoneal administration of Etifoxine resulted in weight loss and decreased serum cholesterol and triglycerides. Obese mice had increased hepatic transcripts associated with lipid metabolism (cyp7a1, cyp27a1, abcg1 and LXRα) and inflammatory factors (TNFα and IL18) but these effects were reversed after Etifoxine treatment other than cyp7a1. Taxonomic profiles of the organisms from the caecum were generated by 16S rRNA gene sequencing and Obese and Etifoxine mice show differences by diversity metrics, Differential Abundance and functional metagenomics. Organisms in genus Oscillospira and genera from Lachnospiraceae family and Clostridiales order are higher in Control than Obese and at intermediate levels with Etifoxine treatment. With respect to community metabolic potential, Etifoxine mice have characteristics similar to Control and particularly with respect to metabolism of butanoate, sphingolipid, lipid biosynthesis and xenobiotic metabolism. We suggest mechanisms where-by Etifoxine influences processes of host, such as on bile acid synthesis, and microbiota, such as signalling from production of butanoate and sphingosine, resulting in decreased cholesterol, lipids and inflammatory factors. We speculate that the indirect effect of Etifoxine on microbial composition is mediated by microbial β-glucuronidases that metabolise excreted Etifoxine glucuronides.
AB - Obesity is intimately associated with diet and dysbiosis of gut microorganisms but anxiolytics, widely used in treatment of psychiatric conditions, frequently result in weight gain and associated metabolic disorders. We are interested in effects of the anxiolytic Etifoxine, which has not been studied with respect to weight gain or effects on gut microorganisms. Here we induced obesity in mice by feeding a high-fat diet but found that intraperitoneal administration of Etifoxine resulted in weight loss and decreased serum cholesterol and triglycerides. Obese mice had increased hepatic transcripts associated with lipid metabolism (cyp7a1, cyp27a1, abcg1 and LXRα) and inflammatory factors (TNFα and IL18) but these effects were reversed after Etifoxine treatment other than cyp7a1. Taxonomic profiles of the organisms from the caecum were generated by 16S rRNA gene sequencing and Obese and Etifoxine mice show differences by diversity metrics, Differential Abundance and functional metagenomics. Organisms in genus Oscillospira and genera from Lachnospiraceae family and Clostridiales order are higher in Control than Obese and at intermediate levels with Etifoxine treatment. With respect to community metabolic potential, Etifoxine mice have characteristics similar to Control and particularly with respect to metabolism of butanoate, sphingolipid, lipid biosynthesis and xenobiotic metabolism. We suggest mechanisms where-by Etifoxine influences processes of host, such as on bile acid synthesis, and microbiota, such as signalling from production of butanoate and sphingosine, resulting in decreased cholesterol, lipids and inflammatory factors. We speculate that the indirect effect of Etifoxine on microbial composition is mediated by microbial β-glucuronidases that metabolise excreted Etifoxine glucuronides.
KW - Etifoxine
KW - obesity
KW - weight-loss
KW - colonic microbial functionality
KW - QIIME 2
KW - PICRUSt
U2 - 10.1016/j.bcp.2020.114151
DO - 10.1016/j.bcp.2020.114151
M3 - Article
VL - 180
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
M1 - 114151
ER -