Obesity: an inherited metabolic deficiency in the control of macronutrient balance?

It has generally been assumed that the body is 'energy blind' and calories from all three macronutrients contribute with the same value to energy balance. There is, however, accumulating evidence to suggest that during ad-libitum conditions energy balance is achieved by a separate regulation of carbohydrate, fat and protein balances. Regulation of carbohydrate balance has the highest priority in the hierarchy, which is appropriate because the limited glycogen stores are only capable of covering the carbohydrate oxidation for a few days. Due to the higher satiating power of carbohydrate and protein compared with fat, a reduction in the dietary fat/carbohydrate ratio produces a negative fat balance in normal subjects consuming the diet ad libitum, while an increase in dietary fat/carbohydrate ratio results in a positive fat balance and weight gain. Subjects with a genetically determined predisposition to obesity become obese when they are exposed to a particular range of environmental conditions. The available knowledge suggests that the genetic propensity to weight gain is caused by a susceptibility to dietary fat due to an impaired capacity to increase their lipid/carbohydrate oxidation when fed a high-fat/low-carbohydrate diet. This in turn promotes lipid storage, depletion of carbohydrate stores and increases appetite. By enlarging the fat stores, the accompanying insulin resistance and higher levels of circulating non-esterified fatty acids increase lipid oxidation until it is commensurate with the dietary fat intake. The development of obesity may therefore be viewed as a regulatory mechanism by which the impaired lipid oxidation rate is raised to match a high fat intake. However, by decreasing the dietary ratio of fat to carbohydrate, macronutrient balance may be achieved with a high energy expenditure and a normal body composition. The results support current dietary recommendations, but with less emphasis on carbohydrate source, and they are also applicable for the prevention and treatment of obesity.