Vitamin D Deficiency Increases Lipogenesis and Reduces Beta-Oxidation in the Liver of Diet-Induced Obese Mice.

Abstract

The study was conducted to understand better the mechanisms involved in liver changes when there is a combination of diet-induced obesity (DIO) and vitamin D deficiency (VDD). After 8 wk of feeding a control diet (C group) or a high-fat diet (HF), both with vitamin D, and counterpart groups without vitamin D (VitD- groups), we found in plasma: higher alanine aminotransferase, and aspartate aminotransferase in the VitD- groups, and more elevated total cholesterol in the HF group. Compared to their counterparts, HF and HF/VitD- showed hyperinsulinemia and higher hepatic triglycerides and steatosis. The protein expressions of markers linked with the vitamin D action were altered by VDD (vitamin D receptor VDR, 25-hydroxyvitamin D-24-hydroxylase CYP24A1, CYP27B1, and CYP2R1). The hepatic lipogenesis and fatty acid synthesis were enhanced by VDD (peroxisome proliferator-activated receptor PPARγ, sterol regulatory element-binding proteins SREBP1c, carbohydrate-responsive element-binding protein ChREBP, and fatty acid synthase FAS), but markers of beta-oxidation were reduced (PPARα and phosphoenolpyruvate carboxykinase PEPCK). In conclusion, the study provides convincing new evidence that there is an additive and adverse effect on the liver caused by the combination of VDD and DIO. The essence of these changes in the liver is in an increased lipogenesis and a reduced beta-oxidation, which predisposes to the accumulation of fat in the liver, accompanied by IR. The worsening of the pathogenesis of NAFLD may tilt to more severe stages of liver disease.

• Authors: Celina Carvalho Borges, Andreza Fernandes Salles, Isabele Bringhenti, Carlos Alberto Mandarim-DE-Lacerda, Marcia Barbosa Aguila
• Journal: Journal of nutritional science and vitaminology (J Nutr Sci Vitaminol (Tokyo)) Vol. 64 Issue 2 Pg. 106-115 ( 2018) ISSN: 1881-7742 [Electronic] Japan
• PMID: 29710028 (Publication Type: Journal Article)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Dietary Fats
• Mlxipl protein, mouse
• Nuclear Proteins
• PPAR alpha
• Sterol Regulatory Element Binding Protein 1
• Transcription Factors
• Vitamin D
• Fatty Acid Synthases

Topics

• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Diet, High-Fat
• Dietary Fats (administration & dosage, adverse effects)
• Fatty Acid Synthases (metabolism)
• Lipogenesis
• Lipolysis
• Liver (metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Obese
• Non-alcoholic Fatty Liver Disease (etiology, metabolism)
• Nuclear Proteins (metabolism)
• Obesity (complications, metabolism)
• Oxidation-Reduction
• PPAR alpha (metabolism)
• Sterol Regulatory Element Binding Protein 1 (metabolism)
• Transcription Factors (metabolism)
• Vitamin D (metabolism)
• Vitamin D Deficiency (complications, metabolism)