Kakalij Rahul M, Dsouza Del L, Boesen Erika I
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, United States.
Front Physiol. 2022 Jul 6;13:930353. doi: 10.3389/fphys.2022.930353. eCollection 2022.
Metabolic syndrome (MetS) is common in Systemic Lupus Erythematosus (SLE) patients and is associated with increased cardio-renal risk. Toll-like receptor 7 (TLR7) stimulation promotes the development of SLE through mechanisms including activating type I Interferon (IFN) and autoreactive B cells. The current study tested whether combined TLR7 agonist treatment and exposure to a high fat, high sucrose "Western diet" intervention affects the early-stage development of SLE or MetS features. Female C57BL/6 mice were untreated or treated with the TLR7 agonist imiquimod (IMQ) and fed a high-fat diet (HFD; fat 42% kcal, sucrose 34% kcal) or control diet (fat 12.6% kcal, sucrose 34% kcal) for 6 weeks. Supporting early-stage induction of autoimmunity, spleen weights were significantly increased and anti-nuclear antibody (ANA) positivity was detected in IMQ-treated mice. Increased body weight, gonadal fat pad mass, and plasma leptin levels were observed between HFD and control animals for both IMQ and untreated mice. However, the increase in these parameters with HFD was slightly but significantly diminished in IMQ-treated mice. Both the HFD and IMQ treatments significantly increased fasting blood glucose levels. Notably, IMQ treatment affected fasting insulin concentrations in a diet-dependent manner, with hyperinsulinemia observed in IMQ-HFD treated mice. Together, this indicates that the IMQ model of SLE is associated with metabolic alterations, impaired glycemic control, and hyperinsulinemia under HFD conditions. This model may be helpful in further investigating the relationship between MetS and SLE, and supports a role of TLR7 signaling in promoting or accelerating the development of dysglycemia and hyperinsulinemia.
代谢综合征（MetS）在系统性红斑狼疮（SLE）患者中很常见，并且与心血管和肾脏风险增加相关。Toll样受体7（TLR7）刺激通过包括激活I型干扰素（IFN）和自身反应性B细胞在内的机制促进SLE的发展。本研究测试了联合TLR7激动剂治疗以及暴露于高脂肪、高蔗糖的“西方饮食”干预是否会影响SLE或MetS特征的早期发展。雌性C57BL/6小鼠未接受治疗或用TLR7激动剂咪喹莫特（IMQ）治疗，并喂食高脂饮食（HFD；脂肪占42%千卡，蔗糖占34%千卡）或对照饮食（脂肪占12.6%千卡，蔗糖占34%千卡）6周。支持自身免疫的早期诱导，在接受IMQ治疗的小鼠中脾脏重量显著增加且检测到抗核抗体（ANA）阳性。对于接受IMQ治疗和未接受治疗的小鼠，HFD组和对照组动物之间均观察到体重增加、性腺脂肪垫质量增加以及血浆瘦素水平升高。然而，在接受IMQ治疗的小鼠中，HFD导致的这些参数增加略有但显著减少。HFD和IMQ治疗均显著提高了空腹血糖水平。值得注意的是，IMQ治疗以饮食依赖的方式影响空腹胰岛素浓度，在接受IMQ-HFD治疗的小鼠中观察到高胰岛素血症。总之，这表明SLE的IMQ模型与代谢改变、血糖控制受损以及HFD条件下的高胰岛素血症相关。该模型可能有助于进一步研究MetS与SLE之间的关系，并支持TLR7信号在促进或加速血糖异常和高胰岛素血症发展中的作用。
