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Obesity is a result of metabolic imbalance, in particular the imbalance of energy intake and expenditure.Liuwei dihuang is a traditional Chinese herbal formulation and widely used to correct kidney and liver dysfunctions or treat function insufficiencies of these organs.However, it is unknown whether this herbal formulation possesses potential to correct energy metabolic dysfunction and obesity.Therefore, we have conducted several studies in obese rats to investigate the anti-obesity effect of different forms of LWDH, including concentrated pills, ethanol extract, and water extract.Traditionally, LWDH is used in a form of concentrated pills.We tested the anti-obesity effect of LWDH concentrated pills in obese rats.We found that the oral gavage of LWDH concentrated pills dissolved in water significantly reduced weight gain and food/energy intake.There was a significant correlation between food intake and weight gain, indicating that the reduced weight gain by LWDH concentrated pills is at least in part due to a reduction of energy intake.LWDH concentrated pills improved insulin and leptin sensitivities and inhibited inflammation in a dose-dependent manner.The challenge is that the effective dosage is high, which is primarily due to the fact that LWDH is comprised of raw material and ethanol/water extract.In order to identify the active component(s) and lower the effective dosage, LWDH was extracted with ethanol and water separately to generate two separate extracts.In the same animal model, both the ethanol and water extracts significantly reduced weight gain, insulin and/or leptin sensitivities.However, the efficacies are considerably different and in an order of ethanol extract > water extract > concentrated pills.Further analyses revealed that ethanol or water extract lowered weight gain in rats by modulating energy metabolism, i.e., increasing oxygen consumption, enhancing carbohydrate and fat oxidations, and promoting energy expenditure.All these results together suggest that LWDH has potential to prevent weight gain or promote weight loss, possibly through increasing energy expenditure and decreasing energy intake.