The aim of this study was to evaluate the nutritional and behavioral effects of a cafeteria diet in dams during the breastfeeding period and in their offspring from weaning until early adulthood (70 days old). Pregnant Wistar rats were fed a chow diet until delivery. Postnatally (D0), litters were culled to 8 pups and lactating dams received control (CTRL n= 6) or cafeteria (CAF n= 6) diets and water ad libitum. At the end of the breastfeeding period, male offspring were placed in individual boxes receiving the same treatment from their respective dams (CTRL or CAF) until adulthood (70 days). All nutritional and behavioral evaluations were performed with the dams (n= 12) during the breastfeeding phase and with the male offspring (n= 24) after weaning to adulthood. CAF dams demonstrated a lower caloric and protein intake; higher intake of fats; loss of weight; greater accumulation of adipose tissue; and an anxiolytic effect. CAF male offspring showed lower caloric intake; higher intake of fats; and accumulation of adipose tissue. In addition, these animals continued to have decreased body weight, body length and tibia-femur length in relation to CTRL. In dams, a cafeteria diet promoted alterations in body composition and anxiety, and in offspring the diet resulted in adequate development.

Obesity has been reported to be associated with "resistance" to the metabolic effects of leptin. However, previous studies have tested only acute responses to leptin. The purpose of the current study was to test the hypothesis that a high fat (HF) diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague Dawley (SD) rats were fed a HF diet (40% kcal from fat, n=6) or a normal fat diet (NF, 13% kcal from fat, n=5) for 1 year starting at 3 weeks of age. Radiotelemeters were implanted for continuous monitoring of blood pressure (BP) and heart rate (HR). A 21G cannula was placed into the lateral cerebral ventricle (ICV). After recovery and 5 days of control measurements, leptin was infused ICV at 0.02 μg/kg/min for 10 days. Body weight in HF rats was 14% heavier than NF rats (581±17 vs. 510±17 g) and was associated with significantly higher BP (118±2 vs. 96±1 mmHg). Chronic ICV infusion of leptin decreased caloric intake in HF and NF rats similarly (51 ± 4% vs. 42 ± 1%) by day 5, remaining decreased throughout infusion. Despite decreased food intake and weight loss, BP and HR increased during the last 4 days of leptin infusion in both HF and NF rats (5.4 ± 0.6 vs. 5.0 ± 0.5 mmHg and 17 ± 3 vs. 17 ± 2 bpm). These results suggest this model of dietary‐induced obesity does not develop resistance to the chronic effects of central leptin administration on appetite or BP and HR regulation. (NHLBI PO1 HL51971).

Peptide YY3‐36 (PYY3‐36) is secreted by the gastrointestinal tract in response to feeding and has been shown to have anorexic actions during acute systemic injections. The importance of PYY3‐36 in chronic regulation of food intake and cardiovascular function, however, is poorly understood. The purpose of the current study was to test the hypothesis that chronic infusion of PYY3‐36 leads to sustained reductions in food intake and elevations in blood pressure (BP) and heart rate (HR). Sprague Dawley rats (n=7) were instrumented with arterial and venous catheters for continuous monitoring of BP and HR. After recovery and 5 days of control measurements, PYY3‐36 was infused IV for 7 days at a dose of 10 nM/hr. Post‐control measurements were taken for 5 additional days. PYY3‐36 infusion caused a sustained 20% reduction in caloric intake after day 3 (82 ± 2 kcal to 65 ± 2 kcal). BP remained unchanged during PYY3‐36 infusion (+2.8 ± 0.1 mmHg, average change on days 5‐7 of infusion), whereas HR increased significantly (20 ± 1 bpm). Food intake returned to control level within one day after stopping PYY3‐36 infusion. Heart rate, however, did not return to control values until the 2nd day following the termination of PYY3‐36 infusion. Our results indicate that chronic PYY3‐36 infusion caused a sustained reduction in appetite while increasing HR but had no significant effect on chronic blood pressure regulation. (NHLBI ‐ PO1 HL51971).