The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Ann Med. 2023 Dec;55(1):2206162. doi: 10.1080/07853890.2023.2206162.
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.
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).
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.
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.
虽然一项研究发现，在空腹血糖受损、葡萄糖耐量受损和新诊断的 2 型糖尿病患者中，血清 hedgehog 相互作用蛋白（HHIP）浓度显著升高，但肥胖个体循环 HHIP 水平的变化尚不清楚。
采用基因集富集分析和京都基因与基因组百科全书（KEGG）富集分析对差异表达基因和信号通路进行分析。该研究共纳入 452 名年轻女性，其中 248 名肥胖，204 名对照。采用 ELISA 试剂盒检测循环 HHIP 和 Adipoq 水平。对每位受试者进行正常血糖高胰岛素钳夹（EHC）和口服葡萄糖耐量试验（OGTT）。32 名患者给予二甲双胍治疗，49 名患者给予利拉鲁肽治疗 6 周。该研究在中国临床试验注册中心（ChiCTR2000032878 和 ChiCTR1800019776）进行了注册。
肥胖与 cAMP 信号通路显著相关，KEGG 分析表明 HHIP 是一种与 cAMP 信号相关的分泌蛋白。在这项基于人群的队列研究中，我们发现肥胖女性循环 HHIP 水平显著升高，且与体重指数和血糖、血脂、胰岛素、稳态模型评估的胰岛素抵抗、脱氢表雄酮硫酸酯和黄体生成素呈正相关，与 M 值和 Adipoq 呈负相关。胰岛素抵抗（IR）和超重/肥胖与 HHIP 浓度升高有关。OGTT 和 EHC 试验表明，血糖调节循环 HHIP 水平，但调节程度不及胰岛素。二甲双胍和利拉鲁肽治疗后，循环 HHIP 水平降低，而 Adipoq 水平显著升高。
我们的研究结果支持 HHIP 作为预测肥胖和 IR 的潜在生物标志物。此外，靶向 HHIP 的药物可能是治疗肥胖的新策略。
