PMID- 30905785
OWN - NLM
STAT- MEDLINE
DCOM- 20200203
LR  - 20211204
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1865
IP  - 6
DP  - 2019 Jun 1
TI  - Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue 
      inflammation and liver steatosis in obese mice.
PG  - 1567-1578
LID - S0925-4439(19)30081-X [pii]
LID - 10.1016/j.bbadis.2019.03.007 [doi]
AB  - 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.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Jahn, Daniel
AU  - Jahn D
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany.
FAU - Dorbath, Donata
AU  - Dorbath D
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany.
FAU - Schilling, Anne-Kristin
AU  - Schilling AK
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany.
FAU - Gildein, Lisa
AU  - Gildein L
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany.
FAU - Meier, Chantal
AU  - Meier C
AD  - University of Zurich, Institute of Physiology, Zurich, Switzerland.
FAU - Vuille-Dit-Bille, Raphael N
AU  - Vuille-Dit-Bille RN
AD  - University of Zurich, Institute of Physiology, Zurich, Switzerland.
FAU - Schmitt, Johannes
AU  - Schmitt J
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany.
FAU - Kraus, Daniel
AU  - Kraus D
AD  - University Hospital Wurzburg, Division of Nephrology, Wurzburg, Germany.
FAU - Fleet, James C
AU  - Fleet JC
AD  - Purdue University, Department of Nutrition Science, West Lafayette, IN, USA.
FAU - Hermanns, Heike M
AU  - Hermanns HM
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany.
FAU - Geier, Andreas
AU  - Geier A
AD  - University Hospital Wurzburg, Division of Hepatology, Wurzburg, Germany; 
      University Hospital Zurich, Division of Gastroenterology and Hepatology, Zurich, 
      Switzerland. Electronic address: Geier_A2@ukw.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190321
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Angiopoietin-Like Protein 4)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Triglycerides)
RN  - 0 (VDR protein, human)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
SB  - IM
MH  - Adipose Tissue/metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Angiopoietin-Like Protein 4/*genetics/metabolism
MH  - Animals
MH  - Cohort Studies
MH  - Fatty Liver/*genetics/metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation
MH  - Intestinal Mucosa/*metabolism/pathology
MH  - Lipid Metabolism/genetics
MH  - Lipoprotein Lipase/antagonists & inhibitors/*genetics/metabolism
MH  - Liver/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Obese
MH  - Mice, Transgenic
MH  - Middle Aged
MH  - Receptors, Calcitriol/deficiency/*genetics
MH  - Signal Transduction
MH  - Transcription, Genetic
MH  - Transgenes
MH  - Triglycerides/metabolism
OTO - NOTNLM
OT  - Hepatic
OT  - Mouse model
OT  - Non-alcoholic fatty liver disease
OT  - Overweight
EDAT- 2019/03/25 06:00
MHDA- 2020/02/06 06:00
CRDT- 2019/03/26 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2019/03/06 00:00 [revised]
PHST- 2019/03/19 00:00 [accepted]
PHST- 2019/03/25 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/03/26 06:00 [entrez]
AID - S0925-4439(19)30081-X [pii]
AID - 10.1016/j.bbadis.2019.03.007 [doi]
PST - ppublish
SO  - 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.