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骨髓脂肪组织在发育过程或肾上腺素诱导的重塑过程中不表达 UCP1。

Bone marrow adipose tissue does not express UCP1 during development or adrenergic-induced remodeling.

机构信息

Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO, USA.

Department of Cell Biology & Physiology, Washington University School of Medicine, Saint Louis, MO, USA.

出版信息

Sci Rep. 2019 Nov 22;9(1):17427. doi: 10.1038/s41598-019-54036-x.

Abstract

Adipocytes within the skeleton are collectively termed bone marrow adipose tissue (BMAT). BMAT contributes to peripheral and local metabolism, however, its capacity for cell-autonomous expression of uncoupling protein 1 (UCP1), a biomarker of beige and brown adipogenesis, remains unclear. To overcome this, Ucp1-Cre was used to drive diphtheria toxin expression in cells expressing UCP1 (Ucp1). Despite loss of brown adipose tissue, BMAT volume was not reduced in Ucp1 mice. Comparably, in mTmG reporter mice (Ucp1), Ucp1-Cre expression was absent from BMAT in young (3-weeks) and mature (16-weeks) male and female mice. Further, β3-agonist stimulation failed to induce Ucp1-Cre expression in BMAT. This demonstrates that BMAT adipocytes are not UCP1-expressing beige/brown adipocytes. Thus, to identify novel and emerging roles for BMAT adipocytes in skeletal and whole-body homeostasis, we performed gene enrichment analysis of microarray data from adipose tissues of adult rabbits. Pathway analysis revealed genetic evidence for differences in BMAT including insulin resistance, decreased fatty acid metabolism, and enhanced contributions to local processes including bone mineral density through candidate genes such as osteopontin. In sum, this supports a paradigm by which BMAT adipocytes are a unique subpopulation that is specialized to support cells within the skeletal and hematopoietic niche.

摘要

骨骼中的脂肪细胞统称为骨髓脂肪组织(BMAT)。BMAT 有助于外周和局部代谢,但其自主表达解偶联蛋白 1(UCP1)的能力——米色和棕色脂肪生成的生物标志物——仍不清楚。为了解决这个问题,使用 Ucp1-Cre 驱动 UCP1 表达细胞中的白喉毒素表达(Ucp1)。尽管棕色脂肪组织丧失,但 Ucp1 小鼠的 BMAT 体积并未减少。类似地,在 mTmG 报告小鼠(Ucp1)中,Ucp1-Cre 表达在年轻(3 周)和成熟(16 周)雄性和雌性小鼠的 BMAT 中不存在。此外,β3-激动剂刺激未能诱导 BMAT 中的 Ucp1-Cre 表达。这表明 BMAT 脂肪细胞不是表达 UCP1 的米色/棕色脂肪细胞。因此,为了确定 BMAT 脂肪细胞在骨骼和全身稳态中的新的和新兴作用,我们对成年兔子脂肪组织的微阵列数据进行了基因富集分析。通路分析显示了 BMAT 中的遗传差异证据,包括胰岛素抵抗、脂肪酸代谢减少以及通过候选基因(如骨桥蛋白)增强对局部过程(包括骨密度)的贡献。总之,这支持了一种观点,即 BMAT 脂肪细胞是一种独特的亚群,专门用于支持骨骼和造血龛中的细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3861/6874537/b1e2bdcda1eb/41598_2019_54036_Fig1_HTML.jpg

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