Division of Biomedical Sciences; School of Medicine, University of California, Riverside, CA 92521, USA.
Institute for Integrative Genome Biology Bioinformatics Core Facility, University of California, Riverside, CA 92521, USA.
Endocrinology. 2024 Jan 16;165(3). doi: 10.1210/endocr/bqad196.
Obesity is a chronic disease with increasing prevalence worldwide. Obesity leads to an increased risk of heart disease, stroke, and diabetes, as well as endocrine alterations, reproductive disorders, changes in basal metabolism, and stress hormone production, all of which are regulated by the pituitary. In this study, we performed single-cell RNA sequencing of pituitary glands from male mice fed control and high-fat diet (HFD) to determine obesity-mediated changes in pituitary cell populations and gene expression. We determined that HFD exposure is associated with dramatic changes in somatotrope and lactotrope populations, by increasing the proportion of somatotropes and decreasing the proportion of lactotropes. Fractions of other hormone-producing cell populations remained unaffected. Gene expression changes demonstrated that in HFD, somatotropes became more metabolically active, with increased expression of genes associated with cellular respiration, and downregulation of genes and pathways associated with cholesterol biosynthesis. Despite a lack of changes in gonadotrope fraction, genes important in the regulation of gonadotropin hormone production were significantly downregulated. Corticotropes and thyrotropes were the least affected in HFD, while melanotropes exhibited reduced proportion. Lastly, we determined that changes in plasticity and gene expression were associated with changes in hormone levels. Serum prolactin was decreased corresponding to reduced lactotrope fraction, while lower luteinizing hormone and follicle-stimulating hormone in the serum corresponded to a decrease in transcription and translation. Taken together, our study highlights diet-mediated changes in pituitary gland populations and gene expression that play a role in altered hormone levels in obesity.
肥胖是一种全球范围内发病率不断上升的慢性疾病。肥胖会导致心脏病、中风和糖尿病的风险增加，以及内分泌改变、生殖障碍、基础代谢改变和应激激素产生，所有这些都受垂体调节。在这项研究中，我们对喂食对照饮食和高脂肪饮食（HFD）的雄性小鼠的垂体进行了单细胞 RNA 测序，以确定肥胖介导的垂体细胞群体和基因表达变化。我们发现，HFD 暴露与生长激素细胞和催乳素细胞群体的剧烈变化有关，即生长激素细胞的比例增加，催乳素细胞的比例减少。其他激素产生细胞群体的分数不受影响。基因表达变化表明，在 HFD 中，生长激素细胞变得更具代谢活性，与细胞呼吸相关的基因表达增加，与胆固醇生物合成相关的基因和途径下调。尽管促性腺激素细胞群体没有变化，但与促性腺激素激素产生调节相关的基因显著下调。在 HFD 中，促肾上腺皮质激素细胞和促甲状腺激素细胞受影响最小，而促黑素细胞比例减少。最后，我们确定可塑性和基因表达的变化与激素水平的变化有关。血清催乳素降低与催乳素细胞比例降低相对应，而血清中黄体生成素和卵泡刺激素水平降低则与转录和翻译减少相对应。总之，我们的研究强调了饮食介导的垂体细胞群体和基因表达变化在肥胖改变激素水平中发挥的作用。
