Deoxycholic acid supplementation impairs glucose homeostasis in mice

Bile acids are critical contributors to the regulation of whole body glucose homeostasis; however, the mechanisms remain incompletely defined. While the hydrophilic bile acid subtype, ursodeoxycholic acid, has been shown to attenuate hepatic endoplasmic reticulum (ER) stress and thereby improve gluc...

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Published in:PloS one 2018-07, Vol.13 (7), p.e0200908
Main Authors: Zaborska, Karolina E, Lee, Seon A, Garribay, Darline, Cha, Eumee, Cummings, Bethany P
Format: Article
Language:English
Subjects:
Acids
Analysis
Animals
Bile
Bile acids
Biology and Life Sciences
Body weight
Deoxycholic acid
Deoxycholic Acid - adverse effects
Deoxycholic Acid - chemistry
Diagnosis
Diet
Dietary supplements
Dietary Supplements - adverse effects
Endoplasmic reticulum
Endoplasmic Reticulum - drug effects
Endoplasmic Reticulum - metabolism
Food intake
Glucose
Glucose - metabolism
Glucose tolerance
High fat diet
Homeostasis
Homeostasis - drug effects
Hydrophobic and Hydrophilic Interactions
Hydrophobicity
In vivo methods and tests
Insulin
Insulin - metabolism
Insulin resistance
Liver - cytology
Male
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Physical Sciences
Regulations
Rodents
Signal Transduction - drug effects
Signaling
Stress
Stresses
Type 2 diabetes
Ursodeoxycholic acid
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Summary:Bile acids are critical contributors to the regulation of whole body glucose homeostasis; however, the mechanisms remain incompletely defined. While the hydrophilic bile acid subtype, ursodeoxycholic acid, has been shown to attenuate hepatic endoplasmic reticulum (ER) stress and thereby improve glucose regulation in mice, the effect of hydrophobic bile acid subtypes on ER stress and glucose regulation in vivo is unknown. Therefore, we investigated the effect of the hydrophobic bile acid subtype, deoxycholic acid (DCA), on ER stress and glucose regulation. Eight week old C57BL/6J mice were fed a high fat diet supplemented with or without DCA. Glucose regulation was assessed by oral glucose tolerance and insulin tolerance testing. In addition, circulating bile acid profile and hepatic insulin and ER stress signaling were measured. DCA supplementation did not alter body weight or food intake, but did impair glucose regulation. Consistent with the impairment in glucose regulation, DCA increased the hydrophobicity of the circulating bile acid profile, decreased hepatic insulin signaling and increased hepatic ER stress signaling. Together, these data suggest that dietary supplementation of DCA impairs whole body glucose regulation by disrupting hepatic ER homeostasis in mice.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0200908