Protein-energy malnutrition at mid-adulthood does not imprint long-term metabolic consequences in male rats.

Abstract

The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats. At 90days of age, Wistar male rats were fed a low-protein diet (4.0%, LP group) for 30days, whereas control rats were fed a normal-protein diet (20.5%, NP group) throughout their lifetimes. To allow for dietary rehabilitation, from 120 to 180days of age, the LP rats were fed a normal-protein diet. Then, we measured body composition, fat stores, glucose-insulin homeostasis and pancreatic islet function. At 120days of age, just after low-protein diet treatment, the LP rats displayed a strong lean phenotype, hypoinsulinemia, as assessed under fasting and glucose tolerance test conditions, as well as weak pancreatic islet insulinotropic response to glucose and acetylcholine (p<0.01). At 180days of age, after poor-protein diet rehabilitation, the LP rats displayed a slight lean phenotype (p<0.05), which was associated with a high body weight gain (p<0.001). Additionally, fat pad accumulation, glycemia and insulinemia, as well as the pancreatic islet insulinotropic response, were not significantly different between the LP and NP rats (p>0.05). Taken together, the present data suggest that the effects of dietary restriction as a stressor in adulthood are reversible with dietary rehabilitation, indicating that adulthood is not a sensitive or critical time window for metabolic programming.