E4orf1 improves adipose tissue-specific metabolic risk factors and indicators of cognition function in a mouse model of Alzheimer's disease.
E4orf1 improves adipose tissue-specific metabolic risk factors and indicators of cognition function in a mouse model of Alzheimer's disease.
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DOI：
10.1038/s41387-023-00242-6
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发表时间：
2023-08-12
影响因子：
6.1
通讯作者：
Hegde, Vijay
中科院分区：
文献类型：
--
作者：
Khan, Md Shahjalal Hossain;Hefner, Marleigh;Reddy, Arubala;Dhurandhar, Nikhil V. V.;Hegde, Vijay
肥胖、血糖控制受损和肝脂肪变性通常共存，并且是发展痴呆和阿尔茨海默病（AD）的风险因素。我们假设，一种改善血糖控制和脂肪变性的治疗药物可能会减弱肥胖相关的痴呆进展。我们以前发现，腺病毒蛋白E4 orf 1改善血糖控制和减少肝脏脂肪变性，尽管肥胖的小鼠。在这里，我们确定E4 orf 1的这种代谢改善是否会改善AD转基因小鼠模型的认知能力下降。14至20个月大的APP/PS1/E4 orf 1和APP/PS1（对照）小鼠喂食高脂肪饮食。认知功能测定采用Morris水迷宫（MWM）。测定全身血糖控制和脂肪组织、肝脏和大脑中代谢信号的变化。与对照组相比，E4 orf 1表达显著改善葡萄糖清除率，降低内源性胰岛素需求，降低体脂，增强脂肪组织中的葡萄糖和脂质代谢，并减少肝脏中的从头脂肪生成。在大脑中，E4 orf 1小鼠显示出参与神经发生和淀粉样蛋白β降解的基因的显著更高表达，并且在MWM测试中表现更好。这项研究开启了解决血糖控制和脂肪变性以减轻肥胖相关认知能力下降的可能性。它还强调了E4 orf 1用于该目的的潜力，需要进一步研究。
Obesity, impaired glycemic control, and hepatic steatosis often coexist and are risk factors for developing dementia, and Alzheimer’s disease (AD). We hypothesized that a therapeutic agent that improves glycemic control and steatosis may attenuate obesity-associated progression of dementia. We previously identified that adenoviral protein E4orf1 improves glycemic control and reduces hepatic steatosis despite obesity in mice. Here, we determined if this metabolic improvement by E4orf1 will ameliorate cognitive decline in a transgenic mouse model of AD. Fourteen- to twenty-month-old APP/PS1/E4orf1 and APP/PS1 (control) mice were fed a high-fat diet. Cognition was determined by Morris Water Maze (MWM). Systemic glycemic control and metabolic signaling changes in adipose tissue, liver, and brain were determined. Compared to control, E4orf1 expression significantly improved glucose clearance, reduced endogenous insulin requirement and lowered body-fat, enhanced glucose and lipid metabolism in adipose tissue, and reduced de novo lipogenesis in the liver. In the brain, E4orf1 mice displayed significantly greater expression of genes involved in neurogenesis and amyloid-beta degradation and performed better in MWM testing. This study opens-up the possibility of addressing glycemic control and steatosis for attenuating obesity-related cognitive decline. It also underscores the potential of E4orf1 for the purpose, which needs further investigations.
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DOI：
10.1016/s1474-4422(14)70085-7
发表时间：
2014-09
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Kiliaan AJ;Arnoldussen IA;Gustafson DR
通讯作者：
Gustafson DR
影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
通讯作者：
Gerton, Brooke
影响因子：
6.9
作者：
Hildreth, Kerry L.;Van Pelt, Rachael E.;Schwartz, Robert S.
通讯作者：
Schwartz, Robert S.
肥胖、2 型糖尿病和阿尔茨海默病。
影响因子：
4
作者：
Luchsinger, Jose A.;Gustafson, Deborah R.
通讯作者：
Gustafson, Deborah R.
影响因子：
4.1
作者：
Mostofinejad Z;Akheruzzaman M;Abu Bakkar Siddik M;Patkar P;Dhurandhar NV;Hegde V
通讯作者：
Hegde V