Evidence map›Paper›PMID 42834123›Full record

ArticleEMBO reports2026

Intestinal FXR agonism synergizes with leptin to improve obesity by reducing appetite via secretin.

Xiaochai Zhu, Kang Wang, Huijian Hu, Yitong Guo, Shuang Cui, Ming Cui, An Chen, Jingru Bai, Yidan Ma, Maosheng Gong and 5 more

Abstract read
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In one paragraph

Article in EMBO reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

15 authors.

Xiaochai Zhu *State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Kang Wang *State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Huijian Hu *State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Yitong Guo *State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Shuang CuiState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Ming CuiState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
An ChenState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Jingru BaiState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.ORCID http://orcid.org/0009-0004-1165-4525
Yidan MaState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Maosheng GongState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Guangji WangState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Lijuan CaoState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
Xiaowei XuState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China. xw@cpu.edu.cn.ORCID http://orcid.org/0000-0003-1886-2728
Haiping HaoState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China. haipinghao@cpu.edu.cn.ORCID http://orcid.org/0000-0003-2522-7546
Hong WangState Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China. wanghong@cpu.edu.cn.ORCID http://orcid.org/0000-0002-6192-3082

Funding

111 Plan | Overseas Expertise Introduction Project for Discipline Innovation G20582017001Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China JYB2025XDXM601Major Science and Technology Project of Jiangsu Province BG2024045Major State Basic Research Development Program of China 2022YFA1303800 and 2021 YFA1301300National Natural Science Foundation of China 82373946,82073926,82321005,82530122,and 81930109Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University SKLNMZZ202402Project Program of Basic Science Research Center Base of Yantai Uniiversity P202404
6 · The paper itself

Abstract

Obesity is a chronic condition and is closely associated with various metabolic diseases. It has become a global health concern, and effective pharmacotherapies are urgently needed. Farnesoid X receptor (FXR) is widely regarded as a pivotal target for the treatment of metabolic diseases because of its many biological functions. To avoid the possible adverse side effects of systemic FXR agonism, intestinal-specific FXR agonists have been developed. They show excellent anti-obesity effects, but the underlying mechanism remains unclear. In this study, we demonstrate that intestinal-restricted FXR agonists exhibit marked anti-obesity effects in diet-induced obesity (DIO) and db/db mice, but not in ob/ob mice. Mechanistically, they suppress appetite to reduce obesity in leptin-dependent and secretin-dependent manners. Intestinal FXR agonism upregulates secretin (SCT) expression in the presence of leptin. Specifically, FXR agonism enhances histone H3K4 methylation at the Sct locus, while leptin per se suppresses DNA methylation at the same locus in a leptin-receptor independent manner. Collectively, the results of this study clarify the anti-obesity mechanism underlying intestinal FXR agonists.

Identifiers

PMID42834123

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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.