Noggin depletion in adipocytes promotes obesity in mice
Noggin depletion in adipocytes promotes obesity in mice
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DOI：
10.1016/j.molmet.2019.04.004
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发表时间：
2019-07-01
影响因子：
8.1
通讯作者：
Bostrom, Kristina I.
中科院分区：
文献类型：
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作者：
Blazquez-Medela, Ana M.;Jumabay, Medet;Bostrom, Kristina I.
目的：肥胖症已经增加到流行水平，新的治疗策略需要加强对脂肪调节的理解。虽然骨形态发生蛋白（BMP）影响脂肪形成，但BMP拮抗剂如Noggin的作用在很大程度上是未知的。本研究的目的是确定Noggin，一种细胞外BMP抑制剂，在脂肪形成中的作用。方法：我们使用脂联素cre转基因小鼠产生脂肪来源的祖细胞和脂肪细胞特异性Noggin缺失的小鼠模型，并确定Noggin缺陷的脂肪表型。我们的研究表明，Noggin在祖细胞中表达，但在脂肪细胞中下降，可能导致脂质积累。相应地，体内脂肪细胞特异性Noggin缺失促进了两种性别的年龄相关性肥胖，而食物摄入量没有变化。尽管Noggin的缺失导致两种性别的白色脂肪组织肥大，以及棕色脂肪组织变白和功能受损，但存在明显的性别差异，女性受影响最大。雌性动物棕色脂肪标记物和产热基因的表达受到抑制，包括过氧化物酶体增殖物激活受体γ共激活因子1 α（PGC1 α）和解偶联蛋白1（UCP1）以及与脂肪生成和脂质代谢相关的基因。另一方面，雄性的一些BAT标记物和产热基因发生了早期变化，但主要变化是与脂肪形成和脂质代谢相关的基因。进一步的表征显示，两种性别的VO 2、VCO 2和RER都有所减少，而女性的产热也有所减少。头蛋白也减少饮食诱导的肥胖在近交系小鼠符合肥胖表型的头蛋白缺陷mice.Conclusions：BMP信号调节女性和男性脂肪形成通过不同的代谢途径。通过选择BMP拮抗剂调节脂肪组织代谢可能是长期调节与年龄相关的体重增加和肥胖的策略。(C)2019作者由Elsevier GmbH出版。
Objective: Obesity has increased to pandemic levels and enhanced understanding of adipose regulation is required for new treatment strategies. Although bone morphogenetic proteins (BMPs) influence adipogenesis, the effect of BMP antagonists such as Noggin is largely unknown. The aim of the study was to define the role of Noggin, an extracellular BMP inhibitor, in adipogenesis.Methods: We generated adipose-derived progenitor cells and a mouse model with adipocyte-specific Noggin deletion using the Adiponectin cre transgenic mouse, and determined the adipose phenotype of Noggin-deficiency.Results: Our studies showed that Noggin is expressed in progenitor cells but declines in adipocytes, possibly allowing for lipid accumulation. Correspondingly, adipocyte-specific Noggin deletion in vivo promoted age-related obesity in both genders with no change in food intake. Although the loss of Noggin caused white adipose tissue hypertrophy, and whitening and impaired function in brown adipose tissue in both genders, there were clear gender differences with the females being most affected. The females had suppressed expression of brown adipose markers and thermogenic genes including peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1alpha) and uncoupling protein 1 (UCP1) as well as genes associated with adipogenesis and lipid metabolism. The males, on the other hand, had early changes in a few BAT markers and thermogenic genes, but the main changes were in the genes associated with adipogenesis and lipid metabolism. Further characterization revealed that both genders had reductions in VO2, VCO2, and RER, whereas females also had reduced heat production. Noggin was also reduced in diet-induced obesity in inbred mice consistent with the obesity phenotype of the Noggin-deficient mice.Conclusions: BMP signaling regulates female and male adipogenesis through different metabolic pathways. Modulation of adipose tissue metabolism by select BMP antagonists may be a strategy for long-term regulation of age-related weight gain and obesity. (C) 2019 The Authors. Published by Elsevier GmbH.