Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids

IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Martin Riecan , Veronika Domanska , Cristina Lupu , Maulin Patel , Michaela Vondrackova , Martin Rossmeisl , Alan Saghatelian , Florea Lupu , Ondrej Kuda
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引用次数: 0

Abstract

Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of sex and Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related to testosterone and Adtrp mRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels. Adtrp deletion had minimal impact on both sexes' metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes, and the role of ADTRP is limited to adipose depots. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex-dependent regulation of human FAHFA metabolism.

Abstract Image

羟基脂肪酸脂肪酸酯代谢的组织特异性性别差异。
羟基脂肪酸的脂肪酸酯(FAHFAs)是一种内源性生物活性脂质,具有抗炎和抗糖尿病的特性。尽管它们具有治疗潜力,但人们对 FAHFA 代谢的性别特异性变化知之甚少。本研究调查了性别和雄激素依赖性 TFPI 调节蛋白(ADTRP)(一种 FAHFA 水解酶)的作用。此外,还利用代谢组学和脂质组学评估了FAHFA水平的组织特异性差异,重点是性腺周围白色脂肪组织(pgWAT)、皮下白色脂肪组织(scWAT)、棕色脂肪组织(BAT)、血浆和肝脏。我们发现,与雄性小鼠相比,雌性小鼠的 pgWAT、scWAT 和 BAT 中的 FAHFA 水平较高。FAHFA 水平与睾酮和 Adtrp mRNA 成反比,在 pgWAT 和 scWAT 中,雌性的表达量明显低于雄性。然而,血浆和肝脏中的 FAHFA 水平在性别上没有明显差异。Adtrp 基因缺失对 pgWAT 雌雄代谢组和脂质组的影响极小。然而,我们在雌性小鼠的 pgWAT 中发现了含有 FAHFAs 的三酰甘油雌酯(FAHFA 代谢库)的内源性水平较高。这些研究结果表明,FAHFA 水平的性别差异主要发生在特定的脂肪细胞储库中,并可能调节脂肪细胞对胰岛素的敏感性,而 ADTRP 的作用仅限于脂肪储库。然而,要充分理解人类 FAHFA 代谢的性别依赖性调节的潜在机制和影响,还需要进一步的研究。
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来源期刊
CiteScore
11.00
自引率
2.10%
发文量
109
审稿时长
53 days
期刊介绍: BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.
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