School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Adipocyte. 2022 Dec;11(1):420-433. doi: 10.1080/21623945.2022.2104783.
Strong links have been reported among trimethylamine N-oxide (TMAO), visceral white adipose tissue (vWAT), and cardiometabolic diseases. However, the effects of TMAO on vWAT in hypertension remained incompletely explored. The impact of a chronic 22-week-long treatment with 1 g/L TMAO on vWAT, and its transcriptional and metabolic changes in spontaneously hypertensive rats (SHRs) were evaluated by serum cytokine measurements, histological analysis, fatty acid determinations, and co-expression network analyses. TMAO increased the serum interleukin-6 levels and insulin secretion in SHRs. The adipocyte size was diminished in the SHR 1 g/L TMAO group. In addition, one kind of monounsaturated fatty acids (cis-15-tetracosenoate) and four kinds of polyunsaturated fatty acids (cis-11,14,17-eicosatrienoic acid, docosatetraenoate, docosapentaenoate n-3, and docosapentaenoate n-6) were elevated by TMAO treatment. Three co-expression modules significantly related to TMAO treatment were identified and pathway enrichment analyses indicated that phagosome, lysosome, fatty acid metabolism, valine, leucine, and isoleucine degradation and metabolic pathways were the most significantly altered biological pathways. This study shed new light on the metabolic roles of TMAO on the vWAT of SHRs. TMAO regulated the metabolic status of vWAT, including reduced lipogenesis and an improved specific fatty acid composition. The mechanisms underlying these effects likely involve phagosome and lysosome pathways.
三甲基胺 N-氧化物（TMAO）、内脏白色脂肪组织（vWAT）和心脏代谢疾病之间存在密切联系。然而，TMAO 对高血压患者 vWAT 的影响仍未得到充分研究。本研究通过血清细胞因子测量、组织学分析、脂肪酸测定和共表达网络分析，评估了慢性给予 1g/L TMAO 22 周对自发性高血压大鼠（SHR）vWAT 及其转录和代谢变化的影响。TMAO 增加了 SHR 血清白细胞介素-6 水平和胰岛素分泌。1g/L TMAO 组大鼠的脂肪细胞体积减小。此外，TMAO 处理还增加了一种单不饱和脂肪酸（顺式-15-二十四碳烯酸）和四种多不饱和脂肪酸（顺式-11,14,17-二十碳三烯酸、二十二碳六烯酸、二十二碳五烯酸 n-3 和二十二碳五烯酸 n-6）的含量。鉴定出 3 个与 TMAO 处理显著相关的共表达模块，通路富集分析表明，吞噬体、溶酶体、脂肪酸代谢、缬氨酸、亮氨酸和异亮氨酸降解和代谢途径是变化最显著的生物学途径。本研究为 TMAO 对 SHRs vWAT 的代谢作用提供了新的视角。TMAO 调节了 vWAT 的代谢状态，包括减少脂肪生成和改善特定脂肪酸组成。这些作用的机制可能涉及吞噬体和溶酶体途径。
