Evidence map›Paper›PMID 41672064›Full record

ArticleCell reports. Medicine2026

Hypothalamic malate dehydrogenase 2 modulates systemic glucose metabolism through oxytocin-mediated thermogenesis.

Ting Yao, Guoming Wu, Yu Zeng, Yinyin Xie, Xiao Cui, Qiongyue Zhang, Chaoying Yan, Zhicheng Cui, Hongyu Gong, Tianze Xiong and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

22 authors.

Ting YaoDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Guoming WuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China.
Yu ZengState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China.
Yinyin XieHuashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
Xiao CuiShanghai Stomatological Hospital & School of Stomatology, The State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Qiongyue ZhangHuashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
Chaoying YanDepartment of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Zhicheng CuiState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China.
Hongyu GongInstitutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010000, China.
Tianze XiongState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China.
Xian LiangHuman Phenome Institute, Fudan University, Shanghai 200032, China.
Yan ZhangHefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.
Ruiqi ZhengDepartment of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Hui WangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China.
Mingchun GaoSchool of Medicine, Shanghai University, Shanghai 200444, China.
Peng ZhangDivision of Metabolic and Bariatric Surgery, General Surgery Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Ru WangSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
Xiao ZhaoDepartment of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Zhihui FengFrontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Lei XiaoShanghai Stomatological Hospital & School of Stomatology, The State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Tiemin LiuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China; Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010000, China; Department of Endocrinology and Metabolism, Zhongshan Hospital, Human Phenome Institute, Fudan University, Shanghai 200032, China.
Zhi ZhangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: z_zhang@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bariatric surgery improves hyperglycemia in obesity and type 2 diabetes (T2D), yet its central mechanisms remain unclear. Through cerebrospinal fluid proteomic profiling of rats, we identify reduced central malate dehydrogenase 2 (MDH2) levels that correlate with surgery-induced restoration of normoglycemia. Central MDH2 blockade with the selective antagonist LW6 attenuates hyperglycemia under high-glucose conditions, independent of its enzymatic activity. Mechanistically, MDH2 inhibition activates oxytocinergic neurons in the hypothalamic paraventricular nucleus (PVN), promoting glucose disposal via sympathetic activation of brown adipose tissue (BAT) thermogenesis. Chemogenetic activation of PVN oxytocin neurons recapitulates this effect, while their silencing, oxytocin receptor blockade, or sympathetic inhibition abolishes LW6's metabolic benefits. PVN-specific Mdh2 deletion abrogates LW6's glucose-lowering effects and impairs systemic glucose homeostasis. LW6 demonstrates robust long-lasting glucose-lowering effects in a T2D mouse model. These findings establish MDH2 as a central glucose modulator and therapeutic target linking hypothalamic signaling to peripheral energy metabolism via an oxytocin-sympathetic nervous system (SNS)-BAT axis.

Indexed as

GlucoseHypothalamusMalate DehydrogenaseOxytocinThermogenesisAdipose Tissue, BrownAnimalsDiabetes Mellitus, Type 2Energy MetabolismMaleMiceMice, Inbred C57BLNeuronsParaventricular Hypothalamic NucleusRatsSympathetic Nervous SystemGlucoseMalate DehydrogenaseOxytocinBATbrown adipose tissuehypothalamusmalate dehydrogenase 2MDH2metabolic surgeryoxytocinSNSsympathetic nervous systemT2Dtype 2 diabetes

Identifiers

PMID41672064
PMCPMC12923983

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.