Alternate-day fasting ameliorated anxiety-like behavior in high-fat diet-induced obese mice

Alternate-day fasting (ADF) has been reported to reduce body weight, neuroinflammation, and oxidative stress damage. However, it is not known whether ADF affects obesity-induced anxiety-like behavior. Here, male C57BL/6 mice were given an alternate fasting and high-fat diet (HFD) or standard chow diet (SD) every other day for 16 or 5 weeks. After the intervention, the degree of anxiety of the mice was evaluated by the open field test (OFT) and the elevated plus maze (EPM) test. Pathological changes in the hippocampus, the expression of Sirt1 and its downstream protein monoamine oxidase A (MAO-A) in the hippocampus, and the expression of 5-hydroxytryptamine (5-HT) were detected. Compared with HFD-fed mice, HFD-fed mice subjected to ADF for 16 weeks had a lower body weight but more brown adipose tissue (BAT), less anxiety behavior, and less pathological damage in the hippocampus, and lower expression of Sirt1 and MAO-A protein and higher 5-HT levels in the hippocampus could be observed. In addition, we noted that long-term ADF intervention could cause anxiety-like behavior in SD mice. Next, we changed the intervention time to 5 weeks. The results showed that short-term ADF intervention could reduce the body weight and increase the BAT mass of SD mice, but it did not affect anxiety. These results indicated that long-term ADF ameliorated obesity-induced anxiety-like behavior and hippocampal damage, but caused anxiety in normal-weight mice. Short-term ADF did not produce adverse emotional reactions in normal-weight mice. Here, we might provide new ideas for the treatment of obesity-induced anxiety.