Phenotypic sexual dimorphism in response to dietary fat manipulation in C57BL/6J mice.
Phenotypic sexual dimorphism in response to dietary fat manipulation in C57BL/6J mice.
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对C57BL/6J小鼠的饮食脂肪操纵的反应表型性二态性。
DOI：
10.1016/j.jdiacomp.2020.107795
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发表时间：
2021-03
影响因子：
3
通讯作者：
Mirmira RG
中科院分区：
文献类型：
--
作者：
Casimiro I;Stull ND;Tersey SA;Mirmira RG
肥胖症和代谢综合征在社会上越来越普遍，其并发症和对治疗的反应表现出性别二态性。高脂饮食诱导的肥胖小鼠模型通常用于代谢疾病和糖尿病的机制和治疗研究。然而，将雌性哺乳动物纳入肥胖研究并不是一种常见的做法，并且导致缺乏关于性别对代谢参数的影响及其对人类的适用性的数据。在这里，我们分析了从4周龄开始的雄性和雌性C57 BL/6 J小鼠，这些小鼠被置于低脂饮食（LFD，10%卡路里来自脂肪）、西方饮食（WD，45%卡路里来自脂肪）或高脂肪饮食（HFD，60%卡路里来自脂肪）。评估身体组成，葡萄糖稳态，胰岛素产生和能量代谢，以及胰腺的组织学分析。与LFD相比，WD和HFD的雄性和雌性C57 BL/6 J小鼠的总体重增加百分比相似，然而，与雌性小鼠相比，雄性小鼠在HFD或WD喂养后体重增加更早。与LFD相比，雄性小鼠保持其热量食物摄入，同时减少其运动活动与WD或HFD，而雌性小鼠增加其热量食物摄入与WD喂养。雌性小鼠的自发活动在WD或HFD喂养后没有显著变化，但雌性小鼠与WD或HFD喂养的雄性小鼠相比表现出增加的能量消耗。在饮食干预的第4、12和20周进行的葡萄糖耐量试验显示，与雌性小鼠相比，雄性小鼠的葡萄糖耐量受损更严重。此外，与WD或LFD相比，雄性小鼠在HFD喂养后表现出胰腺β细胞面积增加以及胰岛素敏感性降低，而雌性小鼠则没有。雄性和雌性C57 BL/6 J小鼠在体重、摄食量、运动活动、能量消耗和β细胞适应性方面表现出显著不同的反应，后者表现出较不显著的表型变化。我们的结论是，这些反应的性质强调需要上下文研究肥胖的病理生理学和治疗方面的性别。
Obesity and the metabolic syndrome are increasingly prevalent in society and their complications and response to treatment exhibit sexual dimorphism. Mouse models of high fat diet-induced obesity are commonly used for both mechanistic and therapeutic studies of metabolic disease and diabetes. However, the inclusion of female mammals in obesity research has not been a common practice, and has resulted in a paucity of data regarding the effect of sex on metabolic parameters and its applicability to humans. Here we analyzed male and female C57BL/6J mice beginning at 4 weeks of age that were placed on a low-fat diet (LFD, 10% calories from fat), a Western Diet (WD, 45% calories from fat), or a high fat diet (HFD, 60% calories from fat). Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were performed. Both male and female C57BL/6J mice had similar increases in total percent body weight gain with both WD and HFD compared to LFD, however, male mice gained weight earlier upon HFD or WD feeding compared to female mice. Male mice maintained their caloric food intake while reducing their locomotor activity with either WD or HFD compared to LFD, whereas female mice increased their caloric food intake with WD feeding. Locomotor activity of female mice did not significantly change upon WD or HFD feeding, yet female mice exhibited increased energy expenditure compared to WD or HFD fed male mice. Glucose tolerance tests performed at 4, 12 and 20 weeks of dietary intervention revealed impaired glucose tolerance that was worse in male mice compared to females. Furthermore, male mice exhibited an increase in pancreatic β cell area as well as reduced insulin sensitivity after HFD feeding compared to WD or LFD, whereas female mice did not. Male and female C57BL/6J mice exhibited strikingly different responses in weight, food consumption, locomotor activity, energy expenditure and β cell adaptation upon dietary manipulation, with the latter exhibiting less striking phenotypic changes. We conclude that the nature of these responses emphasizes the need to contextualize studies of obesity pathophysiology and treatment with respect to sex.
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影响因子：
29
作者：
Mauvais-Jarvis F;Arnold AP;Reue K
通讯作者：
Reue K
影响因子：
4.9
作者：
Grove, K. L.;Fried, S. K.;Greenberg, A. S.;Xiao, X. Q.;Clegg, D. J.
通讯作者：
Clegg, D. J.
影响因子：
4.8
作者：
Francis, J;Chakrabarti, SK;Mirmira, RG
通讯作者：
Mirmira, RG
影响因子：
3.1
作者：
Gelineau RR;Arruda NL;Hicks JA;Monteiro De Pina I;Hatzidis A;Seggio JA
通讯作者：
Seggio JA
影响因子：
8.2
作者：
Beery AK;Zucker I
通讯作者：
Zucker I