Irène Zbinden

Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats.

Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P < 0.0001), but catch-up growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring (P < 0.05), thereby contrasting with the lack of significant differences between DEX and CON. These results suggest that prenatal food restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.

β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

BackgroundInsulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.MethodsMale Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.ResultsIn addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.ConclusionsThese results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

The Fat:Carbohydrate Energy Ratio of the Weaning Diet Programs Later Susceptibility to Obesity in Male Sprague Dawley Rats

Dietary fat intake, which is high during suckling, is markedly reduced when food and drinks are introduced into the diet. We investigated whether alterations in the fat:carbohydrate (CHO) content of the weaning diet influenced the later development of adiposity and insulin sensitivity. Three groups of male rats (24/group) were fed from age 16-37 d (phase I) with weaning diets varying in their fat:CHO energy (E) ratios, 10:70 low-fat, high-CHO (LFHC); 30:50 medium-fat, medium-CHO (MFMC), and 60:30 high-fat, high-CHO (HFLC), on an isocaloric basis. Then, all groups consumed ad libitum first a low-fat diet (13% fat E) for 30 wk (phase II) and subsequently a high-fat diet (45% fat E) for another 18 wk (phase III). At the end of phase I, the group fed the HFLC diet demonstrated higher plasma glucose and insulin responses to an oral glucose tolerance test (P < 0.05), but this effect was transient and did not persist into adulthood (phases II and III). By contrast, when challenged with a high-fat diet later in life (age 35.3-53.3 wk), the LFHC group had greater gains in weight (as percent initial weight) and body fat (as absolute and percent body weight) than the other 2 groups that had been weaned with diets higher in fat (P < 0.04 for all). These results provide evidence that metabolic programming by altering the dietary fat:CHO ratio can occur during the weaning period and emphasizes the importance of the fat:CHO ratio of the complementary diet and its relation to the susceptibility to develop adiposity later in life.