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

Autor: Heike M. Hermanns, Raphael N. Vuille-dit-Bille, C. Meier, Andreas Geier, Anne-Kristin Schilling, Daniel Jahn, D Dorbath, Lisa Gildein, James C. Fleet, Johannes Schmitt, Daniel Kraus
Přispěvatelé: University of Zurich, Geier, Andreas
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Transcription
Genetic
Adipose tissue
Mice
Obese
Calcitriol receptor
Cohort Studies
Mice
0302 clinical medicine
ANGPTL4
polycyclic compounds
Transgenes
Intestinal Mucosa
education.field_of_study
Lipoprotein lipase
digestive
oral
and skin physiology
Fatty liver
Middle Aged
3. Good health
10219 Clinic for Gastroenterology and Hepatology
Adipose Tissue
Liver
Molecular Medicine
lipids (amino acids
peptides
and proteins)
030211 gastroenterology & hepatology
Female
medicine.symptom
Signal Transduction
musculoskeletal diseases
Adult
medicine.medical_specialty
Population
Inflammation
610 Medicine & health
Mice
Transgenic
03 medical and health sciences
Internal medicine
medicine
1312 Molecular Biology
Angiopoietin-Like Protein 4
Animals
Humans
education
Molecular Biology
Triglycerides
Aged
business.industry
Lipid metabolism
medicine.disease
Lipid Metabolism
Fatty Liver
Lipoprotein Lipase
030104 developmental biology
Endocrinology
Gene Expression Regulation
1313 Molecular Medicine
Receptors
Calcitriol
business
Zdroj: Biochimica et biophysica acta. Molecular basis of disease. 1865(6)
ISSN: 1879-260X
Popis: 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.
Databáze: OpenAIRE
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