Weight loss is often temporary and is generally followed by recurrent
weight gain and a relapse of metabolic complications, whose severity may be even greater upon recurrence. Preventing recurrent
obesity, understanding the control of the energy balance subsequent to
weight loss, and reversing the predisposition to
obesity are critical factors that warrant an in-depth study. Several
Kampo medicines, including
daisaikoto, have traditionally been used to manage
obesity, but their mechanisms of action are not well studied and their effects on weight regain are unknown. Here, we investigated the therapeutic potential and mechanism of action of
daisaikoto in a mouse model of recurrent
obesity. The mouse model was established by feeding mice a high-fat diet, followed by a normal chow, and a second course of the high-fat diet.
Daisaikoto inhibited not only
obesity and regaining of weight post-dieting, but also
dysbiosis, thereby overcoming the predisposition to
obesity. Furthermore, we found that recurrent
obesity or long-term consumption of the high-fat diet elevated serum
glucose,
insulin, and
corticosterone levels, and that
daisaikoto lowered serum
cholesterol and
free fatty acid levels. These results are consistent with the hypothesis that this medication may inhibit
lipid absorption by inhibiting pancreatic
lipase. However,
daisaikoto had no effect on the
body weight of lean mice fed a normal chow, suggesting that although this medicine prevents
lipid absorption, it does not cause excessive
weight loss. In conclusion, our results elucidate the mechanisms underlying
daisaikoto activity, and suggest that it may serve as a safe and effective
anti-obesity drug.