Evidence map›Paper›PMID 41291157›Full record

ReviewCell biology and toxicology2025

Hepatocyte nuclear factor 1 in renal lipid metabolism: molecular mechanisms and therapeutic potentials.

Wenhui Zhu, Wenfan Wang, Yayun Wang, Xiaolin Tong, Xingfeng Liu, Lili Zhang, Linhua Zhao

Abstract readReview
In one paragraph

Review in Cell biology and toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Wenhui Zhu *College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, No. 1035, BoShuo Street, Changchun, 130117, China.
Wenfan Wang *College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, No. 1035, BoShuo Street, Changchun, 130117, China.
Yayun Wang *College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, No. 1035, BoShuo Street, Changchun, 130117, China.
Xiaolin TongCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, No. 1035, BoShuo Street, Changchun, 130117, China.
Xingfeng LiuInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1, Xiannongtan Street, Xicheng District, Beijing, 100050, China. xfliu@imm.ac.cn.
Lili ZhangInstitute of Metabolic Diseases, Academy of Chinese Medical Sciences, Guang' Anmen Hospital, China, No.5, Beixiange Street, Xicheng District, Beijing, 100053, China. lilizhang369@163.com.
Linhua ZhaoCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, No. 1035, BoShuo Street, Changchun, 130117, China. melonzhao@163.com.

Funding

Beijing Natural Science Foundation 7244497Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine No.ZYYCXTD-D-202001Noncommunicable Chronic Diseases-National Science and Technology Major Project 2023ZD0509306
6 · The paper itself

Abstract

Kidney disease is increasingly linked to dysregulated lipid metabolism, yet the molecular mechanisms driving renal lipotoxicity remain poorly understood. This review elucidates the pivotal role of the hepatic nuclear factor-1 family (HNF-1α and HNF-1β) in renal lipid homeostasis, integrating clinical and experimental evidence. Functionally, HNF-1 isoforms regulate lipid synthesis, oxidation, and transport via conserved POU domains and transcriptional networks. HNF-1α enhances high-density lipoprotein (HDL)-mediated cholesterol efflux through ApoM, while concurrently regulating PCSK9 to promote LDL receptor (LDLR) endocytosis and degradation, thereby inhibiting cholesterol uptake; whereas, HNF-1β promotes cholesterol synthesis via activation of HMGCR/SREBF2 and modulates the PCSK9-LDLR axis. Additionally, HNF-1β coordinates triglyceride metabolism through farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathways, and regulates mitochondrial fatty acid β-oxidation (FAO) via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). Clinically, HNF-1α (MODY3) and HNF-1β (MODY5) mutations are closely associated with dyslipidemia, proteinuria, and CKD progression, with lipotoxicity serving as a key pathogenic driver. Therapeutic strategies targeting HNF-1 include pharmacological agents (e.g., metformin, GLP-1 agonists) and natural compounds (berberine, resveratrol) that modulate its transcriptional activity, alongside CRISPR and miRNA-based precision interventions. This review summarizes the important and multifaceted role of HNF-1 in renal metabolic disorders, highlighting its potential as a therapeutic target and offering new strategies for precision nephrology.

Indexed as

Hepatocyte Nuclear Factor 1-alphaKidneyLipid MetabolismAnimalsHumansSignal TransductionHepatocyte Nuclear Factor 1-alphaHNF-1Kidney diseaseLipotoxicityRenal lipid metabolismTargeted therapy

Identifiers

PMID41291157
PMCPMC12647356

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.