Alternate-day fasting prevents non-alcoholic fatty liver disease and working memory impairment in diet-induced obese mice.

Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.

Lycopene Supplementation Attenuates Oxidative Stress, Neuroinflammation, and Cognitive Impairment in Aged CD-1 Mice.

The carotenoid pigment lycopene (LYC) possesses several properties, including antioxidative, anti-inflammatory, and neuroprotective properties. This study examined the effects of dietary supplementation with LYC on age-induced cognitive impairment, and the potential underlying mechanisms. Behavioral tests revealed that chronic LYC supplementation alleviated age-associated memory loss and cognitive defects. Histological and immunofluorescence-staining results indicated that LYC treatment reversed age-associated neuronal damage and synaptic dysfunctions in the brain. Additionally, LYC supplementation decreased age-associated oxidative stress via suppression of malondialdehyde levels, which increased glutathione, catalase, and superoxide dismutase activities and the levels of antioxidant-enzyme mRNAs, including those of heme oxygenase 1 and NAD-(P)-H-quinone oxidoreductase-1. Furthermore, LYC supplementation significantly reduced age-associated neuroinflammation by inhibiting microgliosis (Iba-1) and downregulating related inflammatory mediators. Moreover, LYC lowered the accumulation of Aß1-42 in the brains of aged CD-1 mice. Therefore, LYC has the potential for use in the treatment of several age-associated chronic diseases.