Treatment with myo-inositol attenuates binding of the carbohydrate-responsive element-binding protein to the ChREBP-β and FASN genes in rat nonalcoholic fatty liver induced by high-fructose diet.

Abstract

Dietary supplementation with the major lipotrope myo-inositol (MI) potently reduces triglyceride (TG) content and expression levels of the fatty acid synthesis genes, for example, fatty acid synthase (FASN), in rat nonalcoholic fatty liver induced by high-fructose diet. Fatty acid synthesis genes are regulated by the carbohydrate-responsive element-binding protein (ChREBP) that exists in 2 isoforms: ChREBP-α and ChREBP-β. The gene encoding the latter isoform is more responsive to fructose. Because MI repressed the induction of fatty acid synthesis gene expression by high-fructose diet, we hypothesized that MI may reduce binding of ChREBP to the carbohydrate response elements (ChoREs) in the ChREBP-β gene as well as in fatty acid synthesis genes in the liver. Rats were fed high-glucose, high-fructose, or high-fructose diets supplemented with MI (0.05% and 0.25%) for 2 weeks. Hepatic TG content and expression levels of the glucose-6-phosphate dehydrogenase, malic enzyme 1, FASN, acetyl-CoA carboxylase alpha, S14, and ChREBP-β were remarkably elevated in rats fed with high fructose compared with the corresponding levels in high-glucose group. Notably, elevated values of these parameters in high-fructose group were reduced by MI. Similarly, high-fructose-induced ChREBP binding to the ChoREs of the ChREBP-β and FASN genes was nominally decreased by MI. This study showed that treatment with MI reduced elevated TG content and expression of genes related to fatty acid synthesis, such as FASN and ChREBP-β, in rat nonalcoholic fatty liver induced by high-fructose diet. Furthermore, MI treatment nominally decreased increased binding of ChREBP to the ChoREs of ChREBP-β and FASN genes.

• Authors: Masaya Shimada, Yutaro Ichigo, Bungo Shirouchi, Shigeo Takashima, Mizuho Inagaki, Tomoyuki Nakagawa, Takashi Hayakawa
• Journal: Nutrition research (New York, N.Y.) (Nutr Res) Vol. 64 Pg. 49-55 (04 2019) ISSN: 1879-0739 [Electronic] United States
• PMID: 30802722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Dietary Sugars
• Lipotropic Agents
• Mlxipl protein, rat
• Nuclear Proteins
• Sterol Regulatory Element Binding Protein 1
• Thrsp protein, rat
• Transcription Factors
• Triglycerides
• Fructose
• Inositol
• Malate Dehydrogenase
• malate dehydrogenase (decarboxylating)
• Glucosephosphate Dehydrogenase
• FASN protein, rat
• Fatty Acid Synthase, Type I
• Acetyl-CoA Carboxylase

Topics

• Acetyl-CoA Carboxylase (metabolism)
• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (genetics, metabolism)
• Diet (adverse effects)
• Dietary Sugars (administration & dosage, adverse effects, metabolism)
• Dietary Supplements
• Fatty Acid Synthase, Type I (genetics, metabolism)
• Fructose (administration & dosage, adverse effects, metabolism)
• Gene Expression
• Glucosephosphate Dehydrogenase (metabolism)
• Inositol (pharmacology, therapeutic use)
• Lipogenesis (drug effects)
• Lipotropic Agents (pharmacology, therapeutic use)
• Liver (drug effects, metabolism)
• Malate Dehydrogenase (metabolism)
• Male
• Non-alcoholic Fatty Liver Disease (drug therapy, etiology, genetics, metabolism)
• Nuclear Proteins (metabolism)
• Rats, Wistar
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)
• Transcription Factors (metabolism)
• Triglycerides (metabolism)