The Importance of Catch‐up Growth after Early Malnutrition for the Programming of Obesity in Male Rat

Abstract

BIESWAL, FLORENCE, MARIE-THÉ RÈ SE AHN, BRIGITTE REUSENS, PAUL HOLVOET, MARTINE RAES, WILLIAM D. REES, AND CLAUDE REMACLE.The importance of catch-up growth after early malnutrition for the programming of obesity in male rat. Obesity. 2006; 14:1330 -1343. Objective: To investigate whether catch-up growth after maternal malnutrition would favor the development of obesity in adulthood. Research Methods and Procedures: Pregnant rats were submitted to protein or calorie restriction during the course of gestation. During lactation, pups were protein-restricted, normally fed, or overfed [reduced litter size, control (C) diet]. At weaning, rats were transferred to chow or to a hypercaloric diet (HCD) known to induce obesity. Body weight, food intake, blood parameters, glucose tolerance, adipocyte cellularity, and adipose factors contributing to cardiovascular disease development were measured. Results: Protein and calorie restriction during gestation led to growth retardation at birth. If malnutrition was prolonged throughout lactation, adult body weight was permanently reduced. However, growth-retarded offspring overfed during the suckling period underwent a rapid catch-up growth and became heavier than the normally fed Cs. Offspring of calorie-restricted rats gained more weight than those of dams fed protein-restricted diet. Feeding an HCD postnatally amplified the effect of calorie restriction, and offspring that underwent catch-up growth became more obese than Cs. The HCD was associated with hyperphagia, hyperglycemia, hyperinsulinemia, glucose intolerance, insulin resistance, and adipocyte hypertrophy. The magnitude of effects varied depending on the type and the timing of early malnutrition. The expression of genes encoding factors implicated in cardiovascular disease was also modulated differently by early malnutrition and adult obesity. Discussion: Catch-up growth immediately after early malnutrition should be a key point for the programming of obesity.

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition: a protective effect?

“…However, despite this period of increased growth, early undernourished rats fed a CD had a similar increase in body weight compared with control. The timing of the growth restriction appears critical as previous studies indicate that growth restriction during gestation followed by catch-up growth during suckling can increase the risk of obesity in rodents, 30,42 whereas normal gestation but restricted nutrition during suckling reduces the risk of obesity. 6,7,42 From the current study, it is clear that growth restriction during the suckling period of rodents leads to long-term decreases in body weight when fed low-fat chow diet into adulthood.…”

“…[28][29][30] Hence we examined the impact of caloric excess following early energy restriction during the suckling period of rats, on metabolic and cardiovascular consequences of obesity. We focused on key markers of adipogenesis and skeletal muscle energetics, examining the expression of genes important for insulin sensitivity and the metabolism of fatty acids such as CPT-1, peroxisome proliferator-activated receptor-a (PPARa), cytochrome c oxidase 4 (COX4) and AdipoR1 in skeletal muscle as well as the expression of adiponectin, leptin and CPT-1 in WAT.…”

Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

“…Many epidemiological studies have indeed demonstrated that infants born small for gestational age are more prone to develop obesity, hypertension and type 2 diabetes in adulthood. [27][28][29] Experimental studies have further corroborated that rodents and other animal species submitted to protein or calorie restriction during gestation and/or suckling exhibit hyperphagia, [30][31][32][33] insulin resistance, 34,35 reduced leptin sensitivity, 36,37 hepatic steatosis, 38 elevated blood pressure 39,40 and hyperlipidemia. 35,37,38 These observations have been explained by the thrifty phenotype hypothesis, also called metabolic programming or the developmental origins of disease.…”

“…[27][28][29] Experimental studies have further corroborated that rodents and other animal species submitted to protein or calorie restriction during gestation and/or suckling exhibit hyperphagia, [30][31][32][33] insulin resistance, 34,35 reduced leptin sensitivity, 36,37 hepatic steatosis, 38 elevated blood pressure 39,40 and hyperlipidemia. 35,37,38 These observations have been explained by the thrifty phenotype hypothesis, also called metabolic programming or the developmental origins of disease. [41][42][43][44][45] It is hypothesized that perinatal undernutrition sensitizes the offspring to the development of metabolic diseases via epigenetic changes that act during early life to program feeding behavior and energy homeostasis for optimal survival under nutritionallydeficient conditions.…”

“…The C group was fed a control diet containing 20% of protein (200 g protein kg À1 ) whereas the LP group was fed an isocaloric low-protein diet containing 8% of protein (80 g protein kg À1 ).The diets were purchased from Ab Diets (Woerden, The Netherlands) and their composition have been described previously. 35,46 Dams were fed ad libitum and their body weight and daily food intake documented every 4 days during gestation and lactation. The morning on which new born litters were found was designated as P0 and the litter size was adjusted to eight pups per dam maintaining as close to a 1:1, male : female ratio as possible.…”