The Early Life Research Unit, Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham NG7 2UH, UK.
Nottingham Digestive Disease Centre and Biomedical Research Unit, School of Medicine, University of Nottingham NG7 2UH, UK.
Nutrients. 2019 May 13;11(5):1065. doi: 10.3390/nu11051065.
Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n=12) were fed either a standard (10% fat, n=6) or high fat diet (HFD: 45% fat, n=6) for 72h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72h induced rapid weight gain (c. 2.6%) and reduced serum non-esterified fatty acids (NEFA) with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and peroxisome proliferator-activated receptor (PPAR) signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g. nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.
棕色脂肪组织（BAT）的功能可能与其解剖位置和发育起源有关。肩胛间 BAT（iBAT）调节急性宏量营养素代谢，而血管周围 BAT（PVAT）调节血管功能。尽管表型相似，但这些脂肪垫是否对急性营养过剩有不同的反应尚不清楚。鉴于它们独特的解剖位置和发育起源，我们假设 iBAT 和 PVAT 对短暂的营养过剩会有不同的反应。12 周龄的 Sprague-Dawley 大鼠（n=12）分别喂食标准（10%脂肪，n=6）或高脂肪饮食（HFD：45%脂肪，n=6）72 小时，并在体温中性环境中饲养。在评估了全身生理学之后，从两个脂肪垫中收集脂肪用于基因表达和蛋白质组分析。72 小时的 HFD 消耗导致体重快速增加（约 2.6%），血清非酯化脂肪酸（NEFA）减少，而总脂肪或脂肪垫质量没有变化。在 iBAT 中，胰岛素信号和脂质代谢相关基因的上调伴随着脂质相关过程和功能的富集，以及胰高血糖素和过氧化物酶体增殖物激活受体（PPAR）信号通路的富集。在 PVAT 中，HFD 诱导多个代谢途径明显下调，同时伴随着参与细胞凋亡（如 Hdgf 和 Ywaq）和 Toll 样受体信号（Ube2n）的蛋白质丰度增加。还存在与 DNA 相关的过程和功能（如核小体组装和组蛋白交换）以及 RNA 降解和细胞黏附途径的富集。总之，我们表明，iBAT 和 PVAT 对短期营养过剩产生不同的反应，突出了这些脂肪垫在脂肪量变化之前的早期适应。
