Gjb2 V37M改变小鼠对慢性高脂喂养的代谢反应。
Gjb2 V37M Modifies Metabolic Responses to Chronic High-Fat Feeding in Mice.
文献信息
| PMID | 42883849 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Cheng-Yu Hsieh |
| 作者单位 | Department of Otolaryngology-Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan. |
| 期刊 | International journal of molecular sciences |
| SCI 分区 | Q1 |
| IF | 6.3 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
GJB2编码连接蛋白26（Cx26），致病性GJB2变异是遗传性听力损失最常见的遗传原因之一；由于Cx26在包括肝脏、胰腺和脂肪组织在内的代谢相关组织中表达，与听力损失相关的c.109G>A（p.V37M）变异是否也会改变机体对高脂饮食（HFD）暴露的全身代谢反应仍不清楚。将3月龄雄性野生型（WT）和纯合Gjb2 V37M小鼠分配至低脂饮食（LFD）或高脂饮食（HFD）组，形成四个研究组：WT-LFD、WT-HFD、V37M-LFD和V37M-HFD。小鼠随访至12月龄，饮食干预持续9个月。在3、6、9和12月龄评估体重、体重指数（BMI）、空腹血糖、血清甘油三酯和HDL胆固醇。9月龄时进行口服葡萄糖耐量试验，12月龄时测量大网膜脂肪。WT-HFD小鼠体重和BMI呈显著进行性增加，而V37M-HFD小鼠的增加较不明显。12月龄时，V37M-LFD与V37M-HFD小鼠的体重和BMI无显著差异。空腹血糖、葡萄糖耐量、甘油三酯和HDL胆固醇谱在各组间存在差异。大网膜脂肪重量也存在显著差异，尽管唯一显著的事后比较是WT-HFD与V37M-LFD小鼠之间。这些发现表明，Gjb2 V37M与慢性饮食暴露期间不同的体重、血糖和血脂反应相关，提示GJB2变异可能改变机体对慢性高脂喂养的全身代谢适应。
英文摘要
GJB2 encodes connexin 26 (Cx26), and pathogenic GJB2 variants are among the most common genetic causes of hereditary hearing loss; because Cx26 is expressed in metabolically relevant tissues including liver, pancreas, and adipose tissue, whether the hearing-loss-associated c.109G>A (p.V37M) variant also modifies systemic metabolic responses to high-fat diet (HFD) exposure remains unclear. Three-month-old male wild-type (WT) and homozygous Gjb2 V37M mice were assigned to low-fat diet (LFD) or high-fat diet (HFD) groups, generating four study groups: WT-LFD, WT-HFD, V37M-LFD, and V37M-HFD. The mice were followed until 12 months of age, with dietary intervention continued for 9 months. Body weight, body mass index (BMI), fasting blood glucose, serum triglycerides, and HDL cholesterol were assessed at 3, 6, 9, and 12 months. An oral glucose tolerance test was performed at 9 months, and omental fat was measured at 12 months. WT-HFD mice showed marked progressive increases in body weight and BMI, whereas increases were less pronounced in V37M-HFD mice. At 12 months, body weight and BMI did not differ significantly between V37M-LFD and V37M-HFD mice. Fasting glucose, glucose tolerance, triglyceride, and HDL cholesterol profiles differed among groups. Omental fat weight also differed significantly, although the only significant post hoc comparison was between WT-HFD and V37M-LFD mice. These findings indicate that Gjb2 V37M is associated with distinct weight, glycemic, and lipid responses during chronic dietary exposure, suggesting that GJB2 variants may modify systemic metabolic adaptation to chronic high-fat feeding.