Low-dose infusions of leptin into the nucleus of the solitary tract increase sensitivity to third ventricle leptin

Previous studies suggest that weight loss occurs when leptin receptors in both the forebrain and hindbrain are activated. Experiments described here tested whether this integration is mediated through a neural connection or by leptin diffusion through the subarachanoid space. If the hypothalamus and hindbrain communicated through a neural pathway, then a very low dose of leptin infused directly into the nucleus of the solitary tract (NTS) would enhance the response to third ventricle (3V) leptin but would have no effect if infused into the fourth ventricle (4V). A 12-day infusion of 10 ng/24 h into the 4V or the NTS reduced body fat. Leptin at 5 ng/24 h into the 4V or NTS had no effect on food intake or body composition, but infusion of 5 ng of leptin/24 h into the NTS combined with a 3V injection of 0.1 μg of leptin inhibited food intake between 6 and 12 h after injection. Cumulative intake was inhibited for up to 36 h. 3V leptin had no effect on food intake of rats receiving the 4V leptin infusion. Similar results were found using infusions of 5 ng leptin/24 h and a 3V injection of 0.025 μg leptin. These data suggest that activation of leptin receptors in the NTS lowers the threshold for response to leptin in the forebrain through a neural network.

A premeal snack of raisins decreases mealtime food intake more than grapes in young children

The effect of a premeal snack of grapes, raisins, or a mix of almonds and raisins, compared with a water control, on food intake (FI) was examined in 8- to 11-year-old normal-weight (15th to 85th percentile) children. Children randomly received 1 of 4 ad libitum (Experiment 1: 13 boys, 13 girls) or fixed-calorie (150 kcal; Experiment 2: 13 boys, 13 girls) treatments, followed by an ad libitum pizza meal 30 min later. Appetite was measured throughout the study, and FI was measured at 30 min. The ad libitum consumption (Experiment 1) of raisins reduced pizza intake (p < 0.037), compared with water (26%), grapes (22%), and the mixed snack (15%). Cumulative energy intake (in kcal: snack + pizza) was lower after water and raisins than after either grapes or the mixed snack (p < 0.031). As a fixed-calorie (150 kcal) snack (Experiment 2), raisins reduced pizza intake, compared with water (∼11%, p = 0.005), and resulted in a cumulative intake similar to water; however, both grapes and the mixed snack resulted in higher cumulative intakes (p < 0.015). Appetite was lower after all caloric ad libitum snacks (p < 0.003) and after fixed amounts of grapes and the mixed snack (p < 0.037), compared with water. In conclusion, consumption of a premeal snack of raisins, but not grapes or a mix of raisins and almonds, reduces meal-time energy intake and does not lead to increased cumulative energy intake in children.

Principles for interpreting interactions among the multiple systems that influence food intake

The widespread use of molecular biological tools has led to a pronounced increase in the number of signals that are now implicated in the controls of food intake and body weight. However, a complete understanding of the roles of these multiple signals requires that we assess how they interact with one another to alter ingestive behavior. Although many such experiments are being conducted, the methods employed to delineate these interactions are often fraught with interpretive difficulties. The purpose of this article is to explore these difficulties and offer practical advice for minimizing these issues in experiments that seek to explore the important interactions among these signals. In particular, the issues of additive vs. nonadditive results, the use of sub- or suprathreshold dose combinations, and the choosing of multiple-dose analyses are all addressed. Furthermore, the possibilities of using intake measures other than cumulative intake and complementary nonbehavioral endpoints are encouraged.

Role of cholecystokinin in the anorexia produced by duodenal delivery of glucose in rats

We used the type A cholecystokinin receptor (CCK-AR) antagonist devazepide to assess the importance of CCK in mediating the anorexia produced by 2-h duodenal infusions of glucose (9.2, 11.0, and 18.3 mmol.kg-1.h-1) and the glucose dimer maltose (4.5, 6.7, and 8.5 mmol.kg-1.h-1) at the start of the dark period in nonfasted rats with free access to food. Glucose and maltose appeared to inhibit 2- to 3-h food intakes dose dependently from 19 to 91%. The highest doses of glucose and maltose administered suppressed feeding similarly by increasing first meal latency and decreasing meal frequency; lower doses produced less reliable effects on meal patterns. Devazepide appeared to completely reverse the cumulative intake responses and some of the meal pattern responses to the 9.2-mmol.kg-1.h-1 dose of glucose and to partially attenuate responses to the two higher glucose doses and to the minimal effective dose of maltose (6.7 mmol.kg-1.h-1). The magnitudes of these devazepide effects were not statistically different from those produced by devazepide when vehicle was infused duodenally. These results suggest that CCK may play a significant necessary role in mediating the satiety response to duodenal delivery of small but not large loads of glucose.