Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats

Yamazaki, Mirai; Munetsuna, Eiji; Yamada, Hiroya; Ando, Yoshitaka; Mizuno, Genki; Murase, Y.; Kondo, Kanako; Ishikawa, Hiroaki; Teradaira, Ryoji; Suzuki, Kôji; Ohashi, Koji

doi:10.1016/j.lfs.2016.02.020

Cited by 46 publications

(35 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Diet influences the epigenome through such mechanisms as direct provision of methyl donors, 131, 132 differences in macronutrient profile (e.g., high fat, high fructose), 1, 3, 133 and diet-derived microRNAs. 134 …”

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

“…1,3, 133 Skeletal muscle DNA methylation was assessed in 21 healthy men before and after 5 days of high-fat overfeeding (50% extra calories, 60% of kcals from a variety of fats) in a randomized crossover study. The investigators detected DNA methylation changes in >6500 genes, most of which involved genes that were related to inflammation, reproduction, and cancer.…”

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

“…133, 141 In rats that were provided with 20% fructose in their drinking water for 14weeks, mtDNA was hypomethylated and the promoter regions of PPARα and CTP1A were hypermethylated. 133,141 We have observed downregulation of hepatic Pparα gene and protein expression in tx-j versus wild-type mice—prompting us to consider whether a high-fructose diet in WD will downregulate genes further, including Pparα . 104 High-fat-, high-sugar-induced changes to the epigenome have been reversed in rodents after their return to a chow diet.…”

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

See 2 more Smart Citations

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Kieffer

Medici

2017

Liver Research

View full text Add to dashboard Cite

Environmental factors, including diet, exercise, stress, and toxins, profoundly impact disease phenotypes. This review examines how Wilson disease (WD), an autosomal recessive genetic disorder, is influenced by genetic and environmental inputs. WD is caused by mutations in the copper-transporter gene ATP7B, leading to the accumulation of copper in the liver and brain, resulting in hepatic, neurological, and psychiatric symptoms. These symptoms range in severity and can first appear anytime between early childhood and old age. Over 300 disease-causing mutations in ATP7B have been identified, but attempts to link genotype to the phenotypic presentation have yielded little insight, prompting investigators to identify alternative mechanisms, such as epigenetics, to explain the highly varied clinical presentation. Further, WD is accompanied by structural and functional abnormalities in mitochondria, potentially altering the production of metabolites that are required for epigenetic regulation of gene expression. Notably, environmental exposure affects the regulation of gene expression and mitochondrial function. We present the “multi-hit” hypothesis of WD progression, which posits that the initial hit is an environmental factor that affects fetal gene expression and epigenetic mechanisms and subsequent “hits” are environmental exposures that occur in the offspring after birth. These environmental hits and subsequent changes in epigenetic regulation may impact copper accumulation and ultimately WD phenotype. Lifestyle changes, including diet, increased physical activity, stress reduction, and toxin avoidance, might influence the presentation and course of WD, and therefore may serve as potential adjunctive or replacement therapies.

show abstract

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

See 1 more Smart Citation

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Kieffer

Medici

2017

Liver Research

View full text Add to dashboard Cite

show abstract

“…4k and l) could also be a consequence of a reduction in the mtDNMT1 levels due to a decrease in PGC-1α expression. Yamazaki and co-workers71 reported reduced levels of mitochondrial 5-hmC and 5-mC in the liver of high fructose-fed rats compared with control rats71. Further research on the implications of decreases in mtDNA 5-mC and 5-hmC for DKD development is warranted.…”

Section: Discussionmentioning

confidence: 97%

“…The hypermethylation of mtDNA has been observed in retinal endothelial cells exposed to high-glucose conditions and in the retinal microvasculature from human donors with diabetic retinopathy70. The hypomethylation of mtDNA in the liver of high fructose-fed rats has been proposed as a novel underlying mechanism of metabolic syndrome71. In this study, we assessed the global content of kidney mtDNA 5-mC, and to the best of our knowledge, this manuscript provides the first report of mtDNA methylation in the diabetic kidney.…”

Section: Discussionmentioning

confidence: 99%

Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory

Oliveira

Bobadilla

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control.

show abstract

d‐Allulose Supplementation Prevents Diet‐Induced Hepatic Lipid Accumulation via miR‐130‐Mediated Regulation in C57BL/6 Mice

Yamazaki

Okito

Harada

et al. 2022

Molecular Nutrition Food Res

Self Cite

View full text Add to dashboard Cite

Scope d‐allulose is a low‐calorie rare sugar. It has been reported that d‐allulose supplementation significantly inhibits diet‐induced hepatic fat accumulation. However, the underlying molecular mechanisms remain unclear. This study elucidates the mechanism underlying the suppressive effect of d‐allulose on hepatic fat accumulation in terms of miRNA regulation. Methods and results Male C57BL/6 mice are divided into three experimental groups–normal diet and distilled water (CC group), high‐fat diet (HFD) and distilled water (HC group), and HFD and 5% d‐allulose solution (HA group)–and fed the respective diets for 8 weeks. Weight gain is significantly lower in the HA group than that in the HC group, although the caloric intake is the same in both. Histological analysis of liver tissues reveals excessive lipid accumulation in the HC group; this is greatly attenuated in the HA group. Real‐time PCR and western blot analyses demonstrate that, compared to the HC group, the HA group exhibits decreased hepatic PPARγ and CD36 expression. Hepatic miR‐130 expression levels are higher in the HA group than those in the CC and HC groups. Conclusions These results indicate that miRNA changes associated with PPARγ may underlie the suppression of hepatic lipid accumulation induced by d‐allulose intake.

show abstract

Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats

Cited by 46 publications

References 39 publications

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory

d‐Allulose Supplementation Prevents Diet‐Induced Hepatic Lipid Accumulation via miR‐130‐Mediated Regulation in C57BL/6 Mice

Contact Info

Product

Resources

About