Evidence map›Paper›PMID 35863745›Full record

ArticleCellular and molecular gastroenterology and hepatology2022

Hepatic Leptin Signaling Improves Hyperglycemia by Stimulating MAPK Phosphatase-3 Protein Degradation via STAT3.

Xiaohua Huang, Qin He, Heng Zhu, Zhengfeng Fang, Lianqiang Che, Yan Lin, Shengyu Xu, Yong Zhuo, Lun Hua, Jianping Wang and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% of its field
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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. MAP kinase phosphatases in metabolic diseases.Trends in endocrinology and metabolism: TEM · 2026
    Review
  4. Review
  5. Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Hepatocentric Leptin Signaling Modulates Gluconeogenesis via MKP-3.Cellular and molecular gastroenterology and hepatology · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Xiaohua HuangAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China; Key Laboratory of Animal Disease-Resistant Nutrition of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan, China.
Qin HeHallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island; School of international education, Xihua University, Chengdu, Sichuan, China.
Heng ZhuAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Zhengfeng FangAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China; Key Laboratory for Food Science and Human Health, College of Food Science, Sichuan Agricultural University, Ya'an, Sichuan, China.
Lianqiang CheAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Yan LinAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Shengyu XuAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Yong ZhuoAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Lun HuaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Jianping WangAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China.
Yuanfeng ZouCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China.
Chao HuangCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China.
Lixia LiCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China.
Haiyan XuHallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island; Department of Quantitative Biosciences, Merck & Co., Inc., Boston, Massachusetts.
De WuAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China; Key Laboratory of Animal Disease-Resistant Nutrition of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan, China.
Bin FengAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan, China; Key Laboratory of Animal Disease-Resistant Nutrition of Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan, China; Hallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island; Key Laboratory for Food Science and Human Health, College of Food Science, Sichuan Agricultural University, Ya'an, Sichuan, China. Electronic address: fengbin@sicau.edu.cn.
Sichuan Agricultural University · CNBrown University · USXihua University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsObesity-related hyperglycemia, with hepatic insulin resistance, has become an epidemic disease. Central neural leptin signaling was reported to improve hyperglycemia. The aim of this study was to investigate the effect of hepatic leptin signaling on controlling hyperglycemia.

methodsFirst, the effect of leptin signaling on gluconeogenesis was investigated in primary mouse hepatocytes and hepatoma cells. Second, glucose tolerance, insulin tolerance, blood glucose levels, and hepatic gluconeogenic gene expression were analyzed in obese mice overexpressing hepatic OBRb. Third, expression of mitogen-activated protein kinase phosphatase (MKP)-3, phosphorylation level of signal transducer and activator of transcription (STAT) 3, and extracellular regulated protein kinase (ERK) were analyzed in hepatocytes and mouse liver. Fourth, the role of MKP-3 in hepatic leptin signaling regulating gluconeogenesis was analyzed. Lastly, the role of ERK and STAT3 in the regulation of MKP-3 protein by leptin signaling was analyzed.

resultsActivation of hepatic leptin signaling suppressed gluconeogenesis in both hepatocytes and obese mouse liver, and improved hyperglycemia, insulin tolerance, and glucose tolerance in obese mice. The protein level of MKP-3, which can promote gluconeogenesis, was decreased by leptin signaling in both hepatocytes and mouse liver. Mkp-3 deficiency abolished the effect of hepatic leptin signaling on suppressing gluconeogenesis in hepatocytes. STAT3 decreased the MKP-3 protein level, while inactivation of STAT3 abolished the effect of leptin signaling on reducing the MKP-3 protein level in hepatocytes. Moreover, STAT3 could combine with MKP-3 and phospho-ERK1/2, which induced the degradation of MKP-3, and leptin signaling enhanced the combination.

conclusionsHepatic leptin signaling could suppress gluconeogenesis at least partially by decreasing the MKP-3 protein level via STAT3-enhanced MKP-3 and ERK1/2 combination.

Indexed as

HyperglycemiaInsulinsAnimalsBlood GlucoseLeptinLiverMiceMice, ObesePhosphoric Monoester HydrolasesProteolysisBlood GlucoseInsulinsLeptinPhosphoric Monoester HydrolasesERKGluconeogenesisLeptinLiverMKP-3STAT3

Identifiers

PMID35863745
PMCPMC9490031
OpenAlexW4285808728

What OpenQuestion 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 OpenQuestion graph.