Early Protein Restriction and Obesity Independently Induce Hypertension in 1-Year-Old Rats

Abstract

1. Recent studies have revealed a link between fetal and early post-natal, growth retardation and the development of features of the insulin resistance syndrome in later life. Obesity is also a strong risk factor for this syndrome. The aim of this study was to assess whether maternal and early protein restriction, which causes growth retardation, and obesity are risk factors that are independent for the development of certain features of the insulin resistance syndrome, especially hypertension. 2. Pregnant Sprague-Dawley rats were given either 20% or 8% protein isocaloric diets throughout pregnancy and lactation. Female offspring were weaned onto the same diets as their mothers and they remained on these diets until 70 days of age. Half the rats were then given standard laboratory chow, whilst the remainder were fed a highly palatable cafeteria-style diet. Rats were maintained on these diets for the remainder of the study. 3. Rats given the 8% protein diet remained physically lighter than comparable animals fed the 20% protein diet throughout the study. In contrast, cafeteria-fed rats showed excessive weight gain. At 1 year of age the rats had their systolic blood pressures and fasting lipids measured, as well as undergoing an intraperitoneal glucose-tolerance test. 4. Cafeteria-fed rats had worse glucose tolerances than controls and hypertriacylglycerolaemia. The early 8% protein rats had significantly increased blood pressures, as did the cafeteria-fed rats. These increases were additive, suggesting that early protein restriction, and later obesity, are indeed independent risk factors for the development of hypertension.

For Debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure*

“…Studies of blood pressure in the offspring of lowprotein pregnancies have shown it to be strongly influenced by the post-weaning diet [18,19,20]. In our studies of more prolonged low-protein exposure, coupled to the use of diet-induced obesity, both early growth restriction and obesity individually caused raised blood pressure.…”

“…In our studies of more prolonged low-protein exposure, coupled to the use of diet-induced obesity, both early growth restriction and obesity individually caused raised blood pressure. The two influences when added together caused a still further and very substantial increase in blood pressure [20]. Animals subjected to early growth restriction and obesity showed all the main features of the human metabolic syndrome being short, fat, glucose-intolerant, insulin-resistant and hypertriglyceridaemic.…”

Predictive Adaptive Responses to Maternal High-Fat Diet Prevent Endothelial Dysfunction but Not Hypertension in Adult Rat Offspring

“…Despite the frequent use of the maternal protein restriction and global dietary restriction models for investigation of the thrifty phenotype hypothesis, in which adult offspring maintained on standard chow develop hypertension and insulin resistance, [5][6][7][8][9] it is not established whether the offspring are protected from these disorders if raised on the maternal diet. It is known, for example, that if rats are exposed to a protein-restricted diet prenatally and until adulthood (71 days) and then fed a balanced diet, insulin resistance and hypertension ensue, 5 but it is not recorded whether these disorders are prevented by continued feeding of the restricted diet to which the fetus is habituated. Indeed, there is some evidence contrary to the thrifty phenotype hypothesis, because mice exposed to protein restriction during the suckling period alone develop sustained protection against obesity when fed a "cafeteria" diet.…”

Relevance of animal models to human eating disorders and obesity

“…High-fat diet consumption by mothers during pregnancy and lactation has long-term consequences on offspring weight, body fat content, and orexigenic and anorexigenic neuropeptide systems (Guo and Jen 1995;Levin and Govek 1998). Moreover, both maternal undernutrition and maternal type 2 diabetes mellitus during gestation and lactation also predispose adult offspring to obesity and insulin resistance (Fernandez-Twinn et al 2005;Petry et al 1997).…”