Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
Nutrients. 2024 Sep 29;16(19):3301. doi: 10.3390/nu16193301.
The objective of this study was to determine the influence of sex and strain on striatal and nucleus accumbens dopamine neurochemistry and dopamine-related behavior due to a high-saturated-fat diet (HFD). Male and female C57B6/J (B6J) and Balb/cJ (Balb/c) mice were randomly assigned to a control-fat diet (CFD) containing 10% kcal fat/g or a mineral-matched HFD containing 60% kcal fat/g for 12 weeks. Intraperitoneal glucose tolerance testing (IPGTT) and elevated plus maze experiments (EPM) confirmed that an HFD produced marked blunting of glucose clearance and increased anxiety-like behavior, respectively, in male and female B6J mice. Electrically evoked dopamine release in the striatum and reuptake in the nucleus accumbens (NAc), as measured by ex vivo fast scan cyclic voltammetry, was reduced for HFD-fed B6J females. Impairment in glucose metabolism explained HFD-induced changes in dopamine neurochemistry for B6J males and, to a lesser extent, Balb/c males. The relative expressions of protein markers associated with the activation of microglia, ionized calcium binding adaptor molecule (Iba1) and cluster of differentiation molecule 11b (CD11b) in the striatum were increased due to an HFD for B6J males but were unchanged or decreased amongst HFD-fed Balb/c mice. Our findings demonstrate that strain and sex influence the insulin- and microglia-dependent mechanisms of alterations to dopamine neurochemistry and associated behavior due to an HFD.
本研究旨在确定高脂肪饮食（HFD）对纹状体和伏隔核多巴胺神经化学和多巴胺相关行为的性别和品系影响。雄性和雌性 C57B6/J（B6J）和 Balb/cJ（Balb/c）小鼠被随机分配到含有 10%卡路里脂肪/g 的对照脂肪饮食（CFD）或含有 60%卡路里脂肪/g 的矿物匹配 HFD，为期 12 周。腹腔内葡萄糖耐量测试（IPGTT）和高架十字迷宫实验（EPM）证实，HFD 分别使雄性和雌性 B6J 小鼠的葡萄糖清除率显著降低和焦虑样行为增加。通过离体快速扫描循环伏安法测量，纹状体中电诱发的多巴胺释放和伏隔核（NAc）中的多巴胺再摄取减少，HFD 喂养的 B6J 雌性。葡萄糖代谢的损伤解释了 HFD 诱导的 B6J 雄性和在较小程度上 Balb/c 雄性多巴胺神经化学变化。由于 HFD，B6J 雄性纹状体中与小胶质细胞激活相关的蛋白标志物（离子钙结合衔接分子（Iba1）和分化抗原分子 11b（CD11b）的相对表达增加，但在 HFD 喂养的 Balb/c 小鼠中不变或减少。我们的研究结果表明，品系和性别影响胰岛素和小胶质细胞依赖性机制，导致 HFD 引起的多巴胺神经化学和相关行为的改变。
