Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Endocrinology. 2023 Dec 23;165(2). doi: 10.1210/endocr/bqad191.
Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial adenosine triphosphate production and functional endoplasmic reticula. Obesity adds stress to tissues, requiring them to adapt to inflammation and oxidative stress, and adding to their allostatic load. We hypothesized that pituitary function is vulnerable to the stress of obesity. Here, we utilized a 10- to 15-week high-fat diet (HFD, 60%) in a thermoneutral environment to promote obesity, testing both male and female FVB.129P mice. We quantified serum hormones and cytokines, characterized the metabolic phenotype, and defined changes in the pituitary transcriptome using single-cell RNA-sequencing analysis. Weight gain was significant by 3 weeks in HFD mice, and by 10 weeks all HFD groups had gained 20 g. HFD females (15 weeks) had increased energy expenditure and decreased activity. All HFD groups showed increases in serum leptin and decreases in adiponectin. HFD caused increased inflammatory markers: interleukin-6, resistin, monocyte chemoattractant protein-1, and tumor necrosis factorα. HFD males and females also had increased insulin and increased TSH, and HFD females had decreased serum prolactin and growth hormone pulse amplitude. Pituitary single-cell transcriptomics revealed modest or no changes in pituitary cell gene expression from HFD males after 10 or 15 weeks or from HFD females after 10 weeks. However, HFD females (15 weeks) showed significant numbers of differentially expressed genes in lactotropes and pituitary stem cells. Collectively, these studies reveal that pituitary cells from males appear to be more resilient to the oxidative stress of obesity than females and identify the most vulnerable pituitary cell populations in females.
垂体前叶细胞的功能需要高水平的蛋白质合成和分泌，这严重依赖于线粒体三磷酸腺苷的产生和功能内质网。肥胖给组织带来压力，需要它们适应炎症和氧化应激，增加其适应负荷。我们假设垂体功能易受肥胖压力的影响。在这里，我们利用 10-15 周高脂肪饮食（HFD，60%）在热中性环境中促进肥胖，测试雄性和雌性 FVB.129P 小鼠。我们量化了血清激素和细胞因子，描述了代谢表型，并使用单细胞 RNA 测序分析定义了垂体转录组的变化。HFD 小鼠在 3 周时体重明显增加，到第 10 周所有 HFD 组体重增加了 20 克。HFD 雌性（15 周）的能量消耗增加，活动减少。所有 HFD 组的血清瘦素增加，脂联素减少。HFD 导致炎症标志物增加：白细胞介素-6、抵抗素、单核细胞趋化蛋白-1 和肿瘤坏死因子α。HFD 雄性和雌性也有胰岛素增加和 TSH 增加，HFD 雌性的血清催乳素和生长激素脉冲幅度降低。垂体单细胞转录组学显示，HFD 雄性在 10 或 15 周后或 HFD 雌性在 10 周后，垂体细胞基因表达的变化很小或没有。然而，HFD 雌性（15 周）的泌乳细胞和垂体干细胞中有大量差异表达的基因。总的来说，这些研究表明，与雌性相比，雄性垂体细胞对肥胖的氧化应激似乎更有弹性，并确定了雌性中最脆弱的垂体细胞群体。
