RGD Reference Report - Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue inflammation and liver steatosis in obese mice. - Rat Genome Database

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Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue inflammation and liver steatosis in obese mice.

Authors: Jahn, Daniel  Dorbath, Donata  Schilling, Anne-Kristin  Gildein, Lisa  Meier, Chantal  Vuille-Dit-Bille, Raphael N  Schmitt, Johannes  Kraus, Daniel  Fleet, James C  Hermanns, Heike M  Geier, Andreas 
Citation: Jahn D, etal., Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1567-1578. doi: 10.1016/j.bbadis.2019.03.007. Epub 2019 Mar 21.
RGD ID: 14402029
Pubmed: PMID:30905785   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbadis.2019.03.007   (Journal Full-text)


OBJECTIVE: Hypovitaminosis D is common in the obese population and patients suffering from obesity-associated disorders such as type 2 diabetes and fatty liver disease, resulting in suggestions for vitamin D supplementation as a potential therapeutic option. However, the pathomechanistic contribution of the vitamin D-vitamin D receptor (VDR) axis to metabolic disorders is largely unknown.
METHODS: We analyzed the pathophysiological role of global and intestinal VDR signaling in diet-induced obesity (DIO) using global Vdr-/- mice and mice re-expressing an intestine-specific human VDR transgene in the Vdr deficient background (Vdr-/- hTg).
RESULTS: Vdr-/- mice were protected from DIO, hepatosteatosis and metabolic inflammation in adipose tissue and liver. Furthermore, Vdr-/- mice displayed a decreased adipose tissue lipoprotein lipase (LPL) activity and a reduced capacity to harvest triglycerides from the circulation. Intriguingly, all these phenotypes were partially reversed in Vdr-/- hTg animals. This clearly suggested an intestine-based VDR activity on systemic lipid homeostasis. Scrutinizing this hypothesis, we identified the potent LPL inhibitor angiopoietin-like 4 (Angptl4) as a novel transcriptional target of VDR.
CONCLUSION: Our study suggests a VDR-mediated metabolic cross-talk between gut and adipose tissue, which significantly contributes to systemic lipid homeostasis. These results have important implications for use of the intestinal VDR as a therapeutic target for obesity and associated disorders.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Vdr  (vitamin D receptor)

Genes (Mus musculus)
Vdr  (vitamin D (1,25-dihydroxyvitamin D3) receptor)

Genes (Homo sapiens)
VDR  (vitamin D receptor)


Additional Information