Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Int J Mol Sci. 2023 May 3;24(9):8201. doi: 10.3390/ijms24098201.
Type 2 diabetes mellitus (T2DM) is a severe chronic epidemic that results from the body's improper usage of the hormone insulin. Globally, 700 million people are expected to have received a diabetes diagnosis by 2045, according to the International Diabetes Federation (IDF). Cancer and macro- and microvascular illnesses are only a few immediate and long-term issues it could lead to. T2DM accelerates the effect of organ weights by triggering a hyperinflammatory response in the body's organs, inhibiting tissue repair and resolving inflammation. Understanding how genetic variation translates into different clinical presentations may highlight the mechanisms through which dietary elements may initiate or accelerate inflammatory disease processes and suggest potential disease-prevention techniques. To address the host genetic background effect on the organ weight by utilizing the newly developed mouse model, the Collaborative Cross mice (CC). The study was conducted on 207 genetically different CC mice from 8 CC lines of both sexes. The experiment started with 8-week-old mice for 12 weeks. During this period, one group maintained a standard chow diet (CHD), while the other group maintained a high-fat diet (HFD). In addition, body weight was recorded bi-weekly, and at the end of the study, a glucose tolerance test, as well as tissue collection (liver, spleen, heart), were conducted. Our study observed a strong effect of HFD on blood glucose clearance among different CC lines. The HFD decreased the blood glucose clearance displayed by the significant Area Under Curve (AUC) values in both populations. In addition, variation in body weight changes among the different CC lines in response to HFD. The female liver weight significantly increased compared to males in the overall population when exposed to HFD. Moreover, males showed higher heritability values than females on the same diet. Regardless of the dietary challenge, the liver weight in the overall male population correlated positively with the final body weight. The liver weight results revealed that three different CC lines perform well under classification models. The regression results also varied among organs. Accordingly, the differences among these lines correspond to the genetic variance, and we suspect that some genetic factors invoke different body responses to HFD. Further investigations, such as quantitative trait loci (QTL) analysis and genomic studies, could find these genetic elements. These findings would prove critical factors for developing personalized medicine, as they could indicate future body responses to numerous situations early, thus preventing the development of complex diseases.
2 型糖尿病（T2DM）是一种严重的慢性流行疾病，源于身体对胰岛素的不当使用。根据国际糖尿病联合会（IDF）的数据，预计到 2045 年，全球将有 7 亿人被诊断患有糖尿病。它可能导致癌症以及大血管和微血管疾病等直接和长期问题。T2DM 通过触发体内器官的过度炎症反应来加速器官重量的增加，抑制组织修复并解决炎症。了解遗传变异如何转化为不同的临床表现，可能突出饮食因素如何引发或加速炎症性疾病过程的机制，并为潜在的疾病预防技术提供线索。为了利用新开发的小鼠模型——协作交叉小鼠（CC）来解决宿主遗传背景对器官重量的影响。该研究对来自 8 个 CC 品系的 207 只具有不同遗传背景的 CC 雌雄小鼠进行了研究。实验从 8 周龄的小鼠开始，持续 12 周。在此期间，一组维持标准的 chow 饮食（CHD），另一组维持高脂肪饮食（HFD）。此外，每两周记录一次体重，在研究结束时，进行葡萄糖耐量试验以及组织采集（肝脏、脾脏、心脏）。我们的研究观察到 HFD 对不同 CC 品系之间的血糖清除有很强的影响。HFD 降低了两个群体中血糖清除的 AUC 值。此外，不同 CC 品系之间的体重变化因 HFD 而有所不同。在整个群体中，与雄性相比，雌性在暴露于 HFD 时肝脏重量显著增加。此外，雄性在同一饮食上的遗传力值高于雌性。无论饮食是否受到挑战，整个雄性群体的肝脏重量与最终体重呈正相关。肝脏重量的结果表明，三个不同的 CC 品系在分类模型下表现良好。回归结果在不同的器官之间也有所不同。因此，这些品系之间的差异对应于遗传方差，我们怀疑某些遗传因素会导致不同的身体对 HFD 的反应。进一步的研究，如定量性状基因座（QTL）分析和基因组研究，可以发现这些遗传因素。这些发现将成为开发个性化药物的关键因素，因为它们可以早期指示身体对众多情况的未来反应，从而预防复杂疾病的发生。
