Hedgehog interacting protein as a circulating biomarker in women with obesity: a cross-sectional study and intervention studies

Ann Med. 2023 Dec;55(1):2206162. doi: 10.1080/07853890.2023.2206162.

Abstract

Background: Although a study found a significant increase in serum hedgehog interacting protein (HHIP) concentrations in impaired fasting blood glucose, impaired glucose tolerance and newly diagnosed T2DM patients, the variation in circulating HHIP levels in obese individuals remains unknown.

Patients and methods: Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for differentially expressed genes and signal pathways. The study is comprised of a total of 452 young women, including 248 obese individuals and 204 controls. Circulating HHIP and Adipoq levels were determined with ELISA kits. Euglycemic-hyperinsulinemic clamps (EHC) and oral glucose tolerance test (OGTT) were conducted in every subject. 32 women were given metformin and 49 were given liraglutide treatment for 6 weeks. The study was registered with www.chictr.org.cn (ChiCTR2000032878 and ChiCTR1800019776).

Results: Obesity was significantly associated with the cAMP signal pathway, and HHIP was a secreted protein related to cAMP signalling, as determined by KEGG analysis. In this population-based cohort study, we found that the level of circulating HHIP was significantly elevated in obese women, and positively correlated with body mass index and blood glucose, blood lipid, insulin, homeostasis model assessment of insulin resistance, dehydroepiandrostenedione sulphate, and luteinizing hormone, while negatively correlated with M-value and Adipoq. Insulin resistance (IR) and ove™rweight/obesity were associated with the higher HHIP concentration. OGTT and EHC tests revealed that the levels of circulating HHIP were regulated by blood glucose but to a less extent by insulin. After therapy with metformin and liraglutide, circulating HHIP levels were decreased, whereas Adipoq levels increased significantly.

Conclusions: Our findings support HHIP as a potential biomarker for predicting obesity and IR. In addition, drugs targeting HHIP may be a new strategy to treat obesity.

Keywords: Hedgehog interacting protein; bioinformatics; insulin resistance; intervention study; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Blood Glucose / metabolism
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Hedgehog Proteins* / blood
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Liraglutide
  • Metformin* / therapeutic use
  • Obesity* / diagnosis

Substances

  • Biomarkers
  • Blood Glucose
  • Hedgehog Proteins
  • Insulin
  • Liraglutide
  • Metformin

Grants and funding

This work was supported by research grants from the Postgraduate research and innovation projects of Chongqing Municipal Education Commission [CYS21221], Natural Science Foundation Project of Chongqing CSTC [cstc2020jcyj-msxmX0952], Chongqing Science and Health Joint Medical Research Project [No. 2022MSXM133], the Health Commission, Chongqing, China [No. 2022MSXM133], Senior Medical Talents Program of Chongqing for Young and Middle-aged [No. 2018GDRC001], China Postdoctoral Science Foundation [2022MD713711], Chongqing Natural Science Foundation Project – Postdoctoral Science Foundation Project [2022NSCQ-BHX0541] and Chongqing Graduate Research and Innovation Project [CYB22203].