Evidence map›Paper›PMID 41545413›Full record

ArticleNature communications2026

Adipocytic sclerostin loop3-LRP4 interaction required by sclerostin to impair whole-body lipid and glucose metabolism.

Hewen Jiang, Xiaohui Tao, Sifan Yu, Yihao Zhang, Yuan Ma, Nanxi Li, Shenghang Wang, Ning Zhang, Xin Yang, Shijian Ding and 19 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

29 authors.

Hewen Jiang *School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Xiaohui Tao *Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Sifan Yu *Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.ORCID http://orcid.org/0000-0003-1117-4199
Yihao Zhang *School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Yuan Ma *School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Nanxi LiGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Shenghang WangGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Ning ZhangSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Xin YangGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Shijian DingGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Chuanxin ZhongGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.ORCID http://orcid.org/0000-0001-9157-8497
Haitian LiGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Zhanghao LiGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Xiaoxin WenGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Huarui ZhangSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Zefeng ChenGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Meiheng SunGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Hang LuoSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Meishen RenGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.
Chongguang LeiSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Yuanyuan YuGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.ORCID http://orcid.org/0000-0003-1276-5695
Jin LiuGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.ORCID http://orcid.org/0000-0001-6308-6719
Zongkang ZhangSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.ORCID http://orcid.org/0000-0003-1646-7871
Aiping LyuGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China.ORCID http://orcid.org/0000-0002-2303-0494
Hui ShengOsteoporosis and Sarcopenia Center, Department of Endocrinology and Metabolism, School of Medicine, Tongji University, The Shanghai Tenth People's Hospital, Shanghai, China. shenghui@tongji.edu.cn.ORCID http://orcid.org/0000-0003-1430-3224
Dijie LiGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China. lidijie@gxnu.edu.cn.ORCID http://orcid.org/0000-0003-4299-5408
Luyao WangGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China. luyaowang@hkbu.edu.hk.ORCID http://orcid.org/0000-0002-2403-8156
Ge ZhangGuangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China. zhangge@hkbu.edu.hk.ORCID http://orcid.org/0000-0002-7807-7695
Bao-Ting ZhangSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China. zhangbaoting@cuhk.edu.hk.ORCID http://orcid.org/0000-0003-1421-0212

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sclerostin, which has three loops, inhibits bone formation and impairs whole-body lipid and glucose metabolism. The marketed therapeutic sclerostin antibody for postmenopausal osteoporosis (POP) mainly targeting loop2 promotes bone formation and improves whole-body lipid and glucose metabolism. However, FDA/EMA warns of its cardiovascular risk. We previously demonstrate that sclerostin loop3 contributes to the inhibitory effect of sclerostin on bone formation but not its cardioprotective effect. Here we find elevated serum sclerostin levels in both POP-T2DM patients and newly-diagnosed T2DM patients and further demonstrate that sclerostin loop3 participates in the impairment effect of sclerostin on whole-body lipid and glucose metabolism in vivo. Mechanistically, specific blockade of adipocytic sclerostin loop3-LRP4 interaction attenuates the impairment effect of sclerostin on lipid and glucose metabolism in vitro and in vivo. This study provides an innovative strategy, blocking adipocytic sclerostin loop3-LRP4 interaction, to normalize lipid and glucose metabolism in POP-T2DM patients, in cardiovascular safety.

Indexed as

Adaptor Proteins, Signal TransducingDiabetes Mellitus, Type 2GlucoseLipid MetabolismOsteoporosis, PostmenopausalAnimalsDiet, High-FatFemaleGene Knock-In TechniquesHumansHypoglycemic AgentsMaleMiceMice, Inbred C57BLOsteogenesisProtein Structure, SecondaryAdaptor Proteins, Signal TransducingGlucoseHypoglycemic AgentsSemaglutideSOST protein, humanSost protein, mouse

Identifiers

PMID41545413
PMCPMC12917164

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.