Comparison of the effects of food versus protein restriction on selected nutritional and inflammatory markers in rats.

We previously demonstrated that feeding a 2% protein AIN-76 diet ad libitum for 14 days resulted in substantial clinical and biochemical changes including weight loss, hypoglycemia, hypoalbuminemia, higher levels of plasma cytokines, oxidative stress in the liver, and activation of inflammatory signaling to interleukin (IL)-6, as compared with a 20% protein diet. In the present study, 54 rats were randomly given a standard rat chow diet ad libitum, or a 25% or 50% reduction of this intake for 14 days. The results showed that weight gain was less in the 25% food-restricted group and halted in the 50% group as compared with the control group. Unlike protein restriction, neither level of food restriction altered plasma levels of albumin and glucose, the hepatic protein abundance of signal transducers and activators of transcriptions and of mitogen-activated protein kinases, or the hepatic contents of total glutathione and malondialdehyde. The intracellular signaling in response to IL-6 stimulation was also well maintained. However, both levels of food restriction elevated IL-1 and corticosterone in plasma, did not alter ghrelin, and decreased plasma levels of free fatty acids. Because these latter 3 markers were not examined previously, 20 rats were fed an AIN-76 diet, either with 20% or 2% protein, ad libitum for 14 days. The 2% protein diet significantly decreased plasma levels of free fatty acids and increased ghrelin and corticosterone as compared with the 20% protein diet. Thus, food restriction, where all essential nutrients are reduced in proportion, is a physiologic stress that, while limiting growth, does not activate or impair the systemic inflammatory response, whereas a very low protein diet with little change in energy intake has a substantial impact on systemic inflammation, body composition, and growth.