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Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Nov 16; Vol. 22 (22). Date of Electronic Publication: 2021 Nov 16. - Publication Year :
- 2021
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Abstract
- Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N -acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet.
- Subjects :
- Aldo-Keto Reductases genetics
Aldo-Keto Reductases metabolism
Amidohydrolases genetics
Amidohydrolases metabolism
Animals
Diet, High-Fat adverse effects
Dietary Sucrose adverse effects
Ethanolamines metabolism
Female
Gene Expression Regulation
Lipid Metabolism drug effects
Lipid Metabolism genetics
Mice
Mice, Inbred C57BL
Monoacylglycerol Lipases genetics
Monoacylglycerol Lipases metabolism
Monoglycerides metabolism
Obesity etiology
Obesity metabolism
Obesity pathology
Phosphoric Diester Hydrolases genetics
Phosphoric Diester Hydrolases metabolism
TRPV Cation Channels genetics
TRPV Cation Channels metabolism
Weight Gain drug effects
Antipsychotic Agents pharmacology
Endocannabinoids metabolism
Gastrointestinal Microbiome drug effects
Obesity drug therapy
Olanzapine pharmacology
Vitamin D pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34830242
- Full Text :
- https://doi.org/10.3390/ijms222212361