Department of Physiology, Louisiana State University Health Sciences Center-New Orleans, New Orleans, LA 70112, USA.
Int J Mol Sci. 2024 Oct 8;25(19):10811. doi: 10.3390/ijms251910811.
Chronic alcohol use leads to metabolic dysfunction in adipose tissue. The underlying mechanisms and the contribution of alcohol-induced adipose tissue dysfunction to systemic metabolic dysregulation are not well understood. In our previous studies, we found that chronic alcohol feeding induces mesenteric lymphatic leakage, perilymphatic adipose tissue (PLAT) inflammation, and local insulin resistance in rats. The goal of this study was to further explore the link between alcohol-induced lymphatic leakage and PLAT immunometabolic dysregulation, locally and systemically, using in vivo and ex vivo approaches. Male rats received a Lieber-DeCarli liquid diet, of which 36% of the calories were from alcohol, for 10 weeks. Time-matched control animals were pair-fed. Adipokine levels were measured in PLAT, subcutaneous fat, plasma, and mesenteric lymph samples. Glucose tolerance was assessed after 10 weeks. Further, we used a novel ex vivo lymph-stimulated naïve PLAT explant approach to modeling lymph leakage to assess changes in adipokine secretion and expression of proinflammatory markers after stimulation with lymph from alcohol- or pair-fed animals. Our data show that chronic alcohol-fed rats presented PLAT-specific decreases in adiponectin and leptin levels, alterations in the expression of genes involved in lipid metabolic pathways, and associated impaired whole-body glucose homeostasis. Further, we found that direct naïve PLAT stimulation with lymph contents from alcohol-fed animals increased IL-6 expression in demonstrating the ability of lymph contents to differentially impact naïve adipose tissue. Overall, chronic alcohol feeding leads to depot-specific alterations in metabolic profile, impaired systemic glucose tolerance, and lymph-induced adipose tissue inflammation. The specific lymph components leading to PLAT immunometabolic dysregulation remain to be determined.
慢性酒精使用会导致脂肪组织代谢功能障碍。酒精引起的脂肪组织功能障碍对全身代谢失调的潜在机制和贡献尚不清楚。在我们之前的研究中，我们发现慢性酒精喂养会诱导大鼠肠系膜淋巴渗漏、周围脂肪组织（PLAT）炎症和局部胰岛素抵抗。本研究的目的是使用体内和体外方法进一步探讨酒精诱导的淋巴渗漏与 PLAT 免疫代谢失调之间的联系，包括局部和全身。雄性大鼠接受 Lieber-DeCarli 液体饮食，其中 36%的热量来自酒精，持续 10 周。时间匹配的对照动物进行配对喂养。测量 PLAT、皮下脂肪、血浆和肠系膜淋巴样品中的脂肪因子水平。10 周后评估葡萄糖耐量。此外，我们使用了一种新的体外淋巴刺激幼稚 PLAT 外植体方法来模拟淋巴渗漏，以评估用酒精或配对喂养动物的淋巴刺激后脂肪因子分泌和促炎标志物表达的变化。我们的数据表明，慢性酒精喂养的大鼠表现出 PLAT 特异性的脂联素和瘦素水平降低、参与脂质代谢途径的基因表达改变以及与全身葡萄糖稳态受损相关。此外，我们发现用来自酒精喂养动物的淋巴内容物直接刺激幼稚 PLAT 会增加 IL-6 的表达，证明了淋巴内容物对幼稚脂肪组织有不同影响的能力。总体而言，慢性酒精喂养会导致特定脂肪组织代谢特征的改变、全身葡萄糖耐量受损和淋巴诱导的脂肪组织炎症。导致 PLAT 免疫代谢失调的特定淋巴成分仍有待确定。
