Visceral adipose tissue-directed FGF21 gene therapy improves metabolic and immune health in BTBR mice.
Visceral adipose tissue-directed FGF21 gene therapy improves metabolic and immune health in BTBR mice.
复制标题
内脏脂肪组织导向的FGF21基因治疗改善BTBR小鼠的代谢和免疫健康。
DOI：
10.1016/j.omtm.2020.12.011
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Cao L
中科院分区：
文献类型：
--
作者：
Queen NJ;Bates R;Huang W;Xiao R;Appana B;Cao L
成纤维细胞生长因子21（FGF 21）是一种肽类激素，作为能量稳态的有效效应物。FGF 21越来越多地被视为2型糖尿病、脂肪肝和其他代谢并发症的有前途的治疗剂。由于不利的药代动力学性质，天然FGF 21肽的外源性施用已被证明是困难的。在这里，我们利用工程血清型腺相关病毒（AAV）载体与双盒设计相结合，选择性地在胰岛素抵抗BTBR T+ Itpr 3 tf/J（BTBR）小鼠的内脏脂肪组织中过表达FGF 21。在高脂肪饮食条件下，AAV-FGF 21的单次低剂量腹膜内注射导致持续的益处，包括改善胰岛素敏感性、血糖加工和全身代谢功能，以及减少全身肥胖、肝脂肪变性、炎性细胞因子和脂肪组织巨噬细胞炎症。我们的研究强调了脂肪组织作为FGF 21基因治疗靶点的潜力，以及微创AAV载体作为代谢性疾病治疗剂的前景。Queen等利用工程病毒载体以非侵入性方式在脂肪组织内施用FGF 21基因治疗。结果，在代谢失调的小鼠模型中，代谢健康得到改善，肥胖相关的脂肪免疫特征减少。
Fibroblast growth factor 21 (FGF21) is a peptide hormone that serves as a potent effector of energy homeostasis. Increasingly, FGF21 is viewed as a promising therapeutic agent for type 2 diabetes, fatty liver disease, and other metabolic complications. Exogenous administration of native FGF21 peptide has proved difficult due to unfavorable pharmacokinetic properties. Here, we utilized an engineered serotype adeno-associated viral (AAV) vector coupled with a dual-cassette design to selectively overexpress FGF21 in visceral adipose tissue of insulin-resistant BTBR T+Itpr3tf/J (BTBR) mice. Under high-fat diet conditions, a single, low-dose intraperitoneal injection of AAV-FGF21 resulted in sustained benefits, including improved insulin sensitivity, glycemic processing, and systemic metabolic function and reduced whole-body adiposity, hepatic steatosis, inflammatory cytokines, and adipose tissue macrophage inflammation. Our study highlights the potential of adipose tissue as a FGF21 gene-therapy target and the promise of minimally invasive AAV vectors as therapeutic agents for metabolic diseases. Queen et al. utilize an engineered viral vector to administer FGF21 gene therapy within adipose tissue in a non-invasive manner. As a result, metabolic health was improved and obesity-associated adipose immune signatures were reduced in a mouse model of dysregulated metabolism.
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影响因子：
7.3
作者：
Frasca D;Blomberg BB
通讯作者：
Blomberg BB
DOI：
10.1016/j.omtm.2020.09.009
发表时间：
2020-12-11
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Bates R;Huang W;Cao L
通讯作者：
Cao L
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
1.2
作者：
Bagchi, Devika P.;MacDougald, Ormond A.
通讯作者：
MacDougald, Ormond A.
DOI：
10.1016/j.bbalip.2018.04.013
发表时间：
2019-01
期刊：
Biochimica et biophysica acta. Molecular and cell biology of lipids
影响因子：
--
作者：
Dewal RS;Stanford KI
通讯作者：
Stanford KI