E4bp4-Cyp3a11 axis in high-fat diet-induced obese mice with weight fluctuation.

IF 3.9 2区医学 Q2 NUTRITION & DIETETICS Nutrition & Metabolism Pub Date : 2024-05-27 DOI:10.1186/s12986-024-00803-1

Shuoshuo Sun, Ruixiang Zhang, Yu Chen, Yijiao Xu, Xingjia Li, Chao Liu, Guofang Chen, Xiao Wei

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Abstract

Objective: Weight regain after weight loss is a challenge in obesity management. The metabolic changes and underlying mechanisms in obese people with weight fluctuation remain to be elucidated. In the present study, we aimed to profile the features and clinical significance of liver transcriptome in obese mice with weight regain after weight loss.

Methods: The male C57BL/6J mice were fed with standard chow diet or high-fat diet (HFD). After 9 weeks, the HFD-induced obese mice were randomly divided into weight gain (WG), weight loss (WL) and weight regain (WR) group. After 10 weeks of dietary intervention, body weight, fasting blood glucose (FBG), intraperitoneal glucose tolerance, triglycerides (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) were measured. Morphological structure and lipid droplet accumulation in the liver were observed by H&E staining and oil red O staining, respectively. The liver transcriptome was detected by RNA sequencing. Protein expressions of liver cytochrome P450 3a11 (Cyp3a11) and E4 promoter-binding protein 4 (E4bp4) were determined by Western blot.

Results: After 10 weeks of dietary intervention, the body weight, FBG, glucose area under the curve, T-CHO and LDL-C in WL group were significantly lower than those in WG group (P < 0.05). At 4 weeks of HFD re-feeding, the mice in WR group presented body weight and T-CHO significantly lower than those in WG group, whereas higher than those in WL group (P < 0.05). Hepatic vacuolar degeneration and lipid droplet accumulation in the liver were significantly alleviated in WL group and WR group, compared to those in WG group. The liver transcriptome associated with lipid metabolism was significantly altered during weight fluctuation in obese mice. Compared with those in WG group, Cyp3a11 in the liver was significantly upregulated, and E4bp4 was significantly downregulated in WL and WR groups.

Conclusion: Obese mice experience weight regain after weight loss by HFD re-feeding, but their glucose and lipid metabolism disorders are milder than those induced by the persistence of obesity. Downregulated E4bp4 and upregulated Cyp3a11 are detected in obese mice after weight loss, suggesting that the E4bp4-Cyp3a11 axis may involved in metabolic mechanisms underlying weight regulation.

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E4bp4-Cyp3a11轴在高脂饮食诱导的肥胖小鼠体重波动中的作用。

目的：减肥后体重反弹是肥胖管理中的一项挑战。肥胖者体重波动时的代谢变化及其内在机制仍有待阐明。在本研究中，我们旨在分析减肥后体重反弹的肥胖小鼠肝脏转录组的特征和临床意义：方法：雄性 C57BL/6J 小鼠以标准饲料或高脂饮食（HFD）喂养。9周后，将高脂饮食诱导的肥胖小鼠随机分为体重增加组（WG）、体重减轻组（WL）和体重恢复组（WR）。饮食干预10周后，测量体重、空腹血糖（FBG）、腹腔葡萄糖耐量、甘油三酯（TG）、总胆固醇（T-CHO）和低密度脂蛋白胆固醇（LDL-C）。通过 H&E 染色和油红 O 染色分别观察了肝脏的形态结构和脂滴堆积。通过 RNA 测序检测了肝脏转录组。通过Western blot检测肝脏细胞色素P450 3a11 (Cyp3a11)和E4启动子结合蛋白4 (E4bp4)的蛋白表达：结果：饮食干预10周后，WL组的体重、FBG、血糖曲线下面积、T-CHO和LDL-C均显著低于WG组（P肥胖小鼠在通过高密度脂蛋白胆固醇（HFD）再喂养减肥后体重会恢复，但其糖代谢和脂代谢紊乱比持续肥胖引起的紊乱要轻微。在减肥后的肥胖小鼠中检测到 E4bp4 下调和 Cyp3a11 上调，这表明 E4bp4-Cyp3a11 轴可能参与了体重调节的代谢机制。

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来源期刊

Nutrition & Metabolism 医学-营养学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects. The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases. Key areas we wish to encourage submissions from include: -how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes; -the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components; -how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved; -how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.