Department of Pharmacology, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait.
Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait City 15462, Kuwait.
Int J Mol Sci. 2022 Aug 2;23(15):8564. doi: 10.3390/ijms23158564.
Leucine-rich α-2 glycoprotein1 (LRG1) is a member of the leucine-rich repeat (LRR) family that is implicated in multiple diseases, including cancer, aging, and heart failure, as well as diabetes and obesity. LRG1 plays a key role in diet-induced hepatosteatosis and insulin resistance by mediating the crosstalk between adipocytes and hepatocytes. LRG1 also promotes hepatosteatosis by upregulating de novo lipogenesis in the liver and suppressing fatty acid β-oxidation. In this study, we investigated the association of LRG1 with obesity markers, including leptin and other adipokines in adolescents (11−14 years; n = 425). BMI-for-age classification based on WHO growth charts was used to define obesity. Plasma LRG1 was measured by ELISA, while other markers were measured by multiplexing assay. Median (IQR) of LRG1 levels was higher in obese (30 (25, 38) µg/mL) and overweight (30 (24, 39) µg/mL) adolescents, compared to normal-weight participants (27 (22, 35) µg/mL). The highest tertile of LRG1 had an OR [95% CI] of 2.55 [1.44, 4.53] for obesity. LRG1 was positively correlated to plasma levels of high sensitivity c-reactive protein (HsCRP) (ρ = 0.2), leptin (ρ = 0.2), and chemerin (ρ = 0.24) with p < 0.001. Additionally, it was positively associated with plasma level of IL6 (ρ = 0.17) and IL10 (ρ = 0.14) but not TNF-α. In conclusion, LRG1 levels are increased in obese adolescents and are associated with increased levels of adipogenic markers. These results suggest the usefulness of LRG1 as an early biomarker for obesity and its related pathologies in adolescents.
富含亮氨酸α-2 糖蛋白 1(LRG1)是富含亮氨酸重复(LRR)家族的成员,与多种疾病有关,包括癌症、衰老、心力衰竭以及糖尿病和肥胖症。LRG1 通过介导脂肪细胞和肝细胞之间的串扰,在饮食诱导的肝脂肪变性和胰岛素抵抗中发挥关键作用。LRG1 还通过上调肝脏中的从头脂肪生成和抑制脂肪酸β-氧化来促进肝脂肪变性。在这项研究中,我们调查了 LRG1 与肥胖标志物(包括青少年(11-14 岁;n=425)中的瘦素和其他脂肪因子)的关联。基于世界卫生组织生长图表的 BMI 年龄分类用于定义肥胖。通过 ELISA 测量 LRG1 水平,通过多重分析测量其他标志物。与正常体重参与者(27(22,35)µg/mL)相比,肥胖(30(25,38)µg/mL)和超重(30(24,39)µg/mL)青少年的 LRG1 中位数(IQR)水平更高。LRG1 的最高三分位值与肥胖的 OR [95%CI]为 2.55 [1.44,4.53]。LRG1 与血浆超敏 C 反应蛋白(HsCRP)(ρ=0.2)、瘦素(ρ=0.2)和 chemerin(ρ=0.24)呈正相关,均 p<0.001。此外,它与血浆白介素 6(IL6)(ρ=0.17)和白介素 10(IL10)(ρ=0.14)呈正相关,但与 TNF-α无关。总之,肥胖青少年的 LRG1 水平升高,并与脂肪生成标志物的水平升高相关。这些结果表明 LRG1 作为肥胖及其相关病理的早期生物标志物在青少年中的有用性。