Evidence map›Paper›PMID 41220714›Full record

ArticleFrontiers in nutrition2025

Paternally multi-generational high-fat diet causes obesity and metabolic disorder through intergenerational DNA methylation.

Tianyi Guo, Zuomin Hu, Liyuan Bao, Yunyun Cao, Zhongxing Chu, Mingzhi Wang, Yan Li, Feijun Luo

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In one paragraph

Article in Frontiers in nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Tianyi GuoShanxi Higher Education Institutions of Science and Technology Innovation Plan Platform, Laboratory of Environmental Factors and Population Health, Key Laboratory of Environmental Pathogenic Mechanisms and Prevention of Chronic Diseases, School of Public Health, Changzhi Medical College, Changzhi, China.
Zuomin HuHunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changzhi, China.
Liyuan BaoShanxi Higher Education Institutions of Science and Technology Innovation Plan Platform, Laboratory of Environmental Factors and Population Health, Key Laboratory of Environmental Pathogenic Mechanisms and Prevention of Chronic Diseases, School of Public Health, Changzhi Medical College, Changzhi, China.
Yunyun CaoHunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changzhi, China.
Zhongxing ChuHunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changzhi, China.
Mingzhi WangShanxi Higher Education Institutions of Science and Technology Innovation Plan Platform, Laboratory of Environmental Factors and Population Health, Key Laboratory of Environmental Pathogenic Mechanisms and Prevention of Chronic Diseases, School of Public Health, Changzhi Medical College, Changzhi, China.
Yan LiDepartment of Endocrinology, Changzhi Key Laboratory of Precision Medicine for Obesity and Metabolic Diseases, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China.
Feijun LuoHunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, Central South University of Forestry and Technology, Changzhi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Paternal high-fat diet (HFD) has detrimental effects on offspring. However, the extent of comprehensive damage and the underlying mechanisms associated with sustained multigenerational HFD exposure remain unclear. This study aims to investigate intergenerational progressive accumulation of obesity and glycolipid metabolic disorders, as well as mechanisms mediated by DNA methylation. Methods: We performed a novel paternally multi-generational HFD consumption model in male C57BL/6 J mice, while excluding maternal gestational effects and any confounding influences from females. The body weight and glycolipid metabolism indicators of each generation of male mice were determined. The intergenerational transmission of CpG methylation and gene expression variation was detected through mRNA microarray, methylated DNA immunoprecipitation (MeDIP)-chip, bisulfite sequencing, RT-qPCR, and Western blot etc. Analysis, to indicate genes involved in glycolipid metabolism related to the intergenerational reprogramming. Results: The HFD caused intergenerational accumulation of body weight increase, disturbance of glycolipid metabolism, and insulin insensitivity in male offspring. MeDIP/gene-chip results indicated that paternal HFD significantly modified gene expression and DNA methylation profiles in the liver and sperm of offspring. The majority of differential genes exhibited hypermethylation in promoter regions and reduced expression in the liver, which were linked to the glucolipid metabolic signaling pathway. The elevated promoter methylation and expression states of Conclusion: This research shows that paternal sustained multi-generational HFD could induce intergenerational progressive accumulation of obesity and metabolic disorder through DNA methylation regulation, and identifies the target genes related to the intergenerational reprogramming, which provides new insights for the establishment of healthy diets and lifestyles.

Indexed as

DNA methylationhigh-fat dietintergenerational inheritancemetabolic disorderobesity

Identifiers

PMID41220714
PMCPMC12597747

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