Sex differences in the lipid profiles of visceral adipose tissue with obesity and gonadectomy.

IF 5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Lipid Research Pub Date : 2025-05-01 Epub Date: 2025-04-15 DOI:10.1016/j.jlr.2025.100803
Mita Varghese, Rajendiran Thekkelnaycke, Tanu Soni, Jiayu Zhang, Krishnarao Maddipati, Kanakadurga Singer
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引用次数: 0

Abstract

In obesity, adipose tissue (AT) expansion is accompanied by chronic inflammation. Altered lipid composition in the visceral or gonadal white AT (GWAT) directly drive AT macrophage accumulation and activation to a proinflammatory phenotype. Sex steroid hormones modulate visceral versus subcutaneous lipid accumulation that correlates with metabolic syndrome, especially in men and postmenopausal women who are more prone to abdominal obesity. Prior studies demonstrated sex differences in GWAT lipid species in HFD-fed mice, but the role of sex hormones is still unclear. We hypothesized that sex hormone alterations with gonadectomy (GX) would further impact lipid composition in the obese GWAT. Untargeted lipidomics of obese GWAT identified sex differences in phospholipids, sphingolipids, sterols, fatty acyls, saccharolipids and prenol lipids. Males had significantly more precursor fatty acids (palmitic, oleic, linoleic, and arachidonic acid) than females and GX mice. Targeted lipidomics for fatty acids and oxylipins in the HFD-fed male and female GWAT stromal vascular fraction identified higher omega-6 to omega-3 free fatty acid profile in males and differences in PUFAs-derived prostaglandins, thromboxanes, and leukotrienes. Both obese male and female GWAT stromal vascular fraction showed increased levels of arachidonic acid-derived oxylipins compared to their lean counterparts. Bulk RNA-seq of sorted GWAT AT macrophages highlighted sex and diet differences in PUFA and oxylipin metabolism genes. These findings of sexual dimorphism in both stored lipid species and PUFA-derived mediators with diet and GX emphasize sex differences in lipid metabolism pathways that drive inflammation responses and metabolic disease risk in obesity.

肥胖和性腺切除术后内脏脂肪组织脂质谱的性别差异。
在肥胖中,脂肪组织(AT)扩张伴随着慢性炎症。内脏或性腺白色AT (GWAT)中脂质组成的改变直接驱动AT巨噬细胞(ATM)的积累和激活,形成促炎表型。性类固醇激素调节与代谢综合征相关的内脏和皮下脂质积累,特别是在男性和绝经后妇女中更容易发生腹部肥胖。先前的研究证实了hfd喂养小鼠的GWAT脂质种类存在性别差异,但性激素在其中的作用尚不清楚。我们假设性腺切除术(GX)的性激素改变会进一步影响肥胖GWAT的脂质组成。肥胖GWAT的非靶向脂质组学鉴定出磷脂、鞘脂、固醇、脂肪酰基、糖脂和戊烯醇脂的性别差异。雄性小鼠的前体脂肪酸(棕榈酸、油酸、亚油酸和花生四烯酸)明显多于雌性和GX小鼠。针对食用hfd的男性和女性GWAT基质血管部分(SVF)的脂肪酸和氧脂素的靶向脂质组学发现,男性中omega-6至omega-3游离脂肪酸含量较高,多不饱和脂肪酸(PUFAs)衍生的前列腺素、血栓烷和白三烯含量也存在差异。肥胖的男性和女性GWAT SVF中花生四烯酸(AA)衍生的氧化脂素水平都比苗条的人高。对已分类的GWAT atm的大量RNA测序突出了PUFA和氧脂代谢基因的性别和饮食差异。这些关于储存脂质物种和PUFA衍生介质与饮食和GX的性别二态性的发现强调了肥胖中驱动炎症反应和代谢性疾病风险的脂质代谢途径的性别差异。
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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
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