A high fat, sugar, and salt Western diet induces motor-muscular and sensory dysfunctions and neurodegeneration in mice during aging: Ameliorative action of metformin

高脂肪、高糖、高盐的西方饮食会导致小鼠在衰老过程中出现运动肌肉和感觉功能障碍以及神经退行性病变:二甲双胍的改善作用

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作者:Song Hong, Aarti Nagayach, Yan Lu, Hongying Peng, Quoc-Viet A Duong, Nicholas B Pham, Christopher A Vuong, Nicolas G Bazan

Aims

To explore the novel linkage between a Western diet combining high saturated fat, sugar, and salt (HFSS) and neurological dysfunctions during aging as well as Metformin intervention, we assessed cerebral cortex abnormalities associated with sensory and motor dysfunctions and cellular and molecular insights in brains using HFSS-fed mice during aging. We also explored the effect of Metformin treatment on these mice.

Conclusion

A HFSS-combined diet caused motor-muscular and sensory dysfunctions, neuroinflammation, and neurodegeneration, whereas metformin counteracted these effects. Our findings show neuroinflammatory consequences of a HFSS diet in aging. Metformin curbs the HFSS-related neuroinflammation eliciting neuroprotection.

Methods

C57BL/6 mice were fed with HFSS and treated with metformin from 20 to 22 months of age, resembling human aging from 56 to 68 years of age (an entry phase of the aged portion of lifespan).

Results

The motor and sensory cortexes in mice during aging after HFSS diet showed: (A) decreased motor-muscular and sensory functions; (B) reduced inflammation-resolving Arg-1+ microglia; (C) increased inflammatory iNOs+ microglia and TNFα levels; (D) enhanced abundance of amyloid-β peptide and of phosphorylated Tau. Metformin attenuated these changes.

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