Altered macronutrient composition and genetics influence the complex transcriptional network associated with adiposity in the Collaborative Cross,Genes and Nutrition

当前位置： X-MOL 学术 › Genes Nutr. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Altered macronutrient composition and genetics influence the complex transcriptional network associated with adiposity in the Collaborative Cross
Genes and Nutrition ( IF 3.3 ) Pub Date : 2022-08-10 , DOI: 10.1186/s12263-022-00714-x
Phoebe Yam _{1,

2} , Melissa VerHague ₃ , Jody Albright ₃ , Erik Gertz ₂ , Fernando Pardo-Manuel de Villena ₄ , Brian J Bennett _{1,

2,

5}

Affiliation

Obesity is a serious disease with a complex etiology characterized by overaccumulation of adiposity resulting in detrimental health outcomes. Given the liver’s critical role in the biological processes that attenuate adiposity accumulation, elucidating the influence of genetics and dietary patterns on hepatic gene expression is fundamental for improving methods of obesity prevention and treatment. To determine how genetics and diet impact obesity development, mice from 22 strains of the genetically diverse recombinant inbred Collaborative Cross (CC) mouse panel were challenged to either a high-protein or high-fat high-sucrose diet, followed by extensive phenotyping and analysis of hepatic gene expression. Over 1000 genes differentially expressed by perturbed dietary macronutrient composition were enriched for biological processes related to metabolic pathways. Additionally, over 9000 genes were differentially expressed by strain and enriched for biological process involved in cell adhesion and signaling. Weighted gene co-expression network analysis identified multiple gene clusters (modules) associated with body fat % whose average expression levels were influenced by both dietary macronutrient composition and genetics. Each module was enriched for distinct types of biological functions. Genetic background affected hepatic gene expression in the CC overall, but diet macronutrient differences also altered expression of a specific subset of genes. Changes in macronutrient composition altered gene expression related to metabolic processes, while genetic background heavily influenced a broad range of cellular functions and processes irrespective of adiposity. Understanding the individual role of macronutrient composition, genetics, and their interaction is critical to developing therapeutic strategies and policy recommendations for precision nutrition.

中文翻译：

改变的宏量营养素组成和遗传学影响协作交叉中与肥胖相关的复杂转录网络

肥胖症是一种具有复杂病因的严重疾病，其特征是肥胖过度积累导致有害的健康结果。鉴于肝脏在减轻肥胖积累的生物过程中的关键作用，阐明遗传和饮食模式对肝脏基因表达的影响是改进肥胖预防和治疗方法的基础。为了确定遗传学和饮食如何影响肥胖的发展，来自遗传多样性重组近交协作杂交 (CC) 小鼠组的 22 个品系的小鼠接受了高蛋白或高脂肪高蔗糖饮食的挑战，然后进行了广泛的表型分析和分析肝基因表达。超过 1000 个由受扰动的膳食常量营养素组成差异表达的基因富集了与代谢途径相关的生物过程。此外，超过 9000 个基因通过菌株差异表达，并富集了与细胞粘附和信号传导有关的生物过程。加权基因共表达网络分析确定了与体脂百分比相关的多个基因簇（模块），其平均表达水平受膳食常量营养素组成和遗传的影响。每个模块都丰富了不同类型的生物功能。遗传背景总体上影响了 CC 中的肝脏基因表达，但饮食常量营养素的差异也改变了特定基因子集的表达。大量营养素组成的变化改变了与代谢过程相关的基因表达，而遗传背景严重影响了广泛的细胞功能和过程，而与肥胖无关。了解常量营养素组成、遗传学及其相互作用的个体作用对于制定精准营养的治疗策略和政策建议至关重要。

更新日期：2022-08-10

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南