Reduction of high-fat diet-induced obesity after chronic administration of brain-derived neurotrophic factor in the hypothalamic ventromedial nucleus.

An acute injection of brain-derived neurotrophic factor (BDNF) in the hypothalamic ventromedial nucleus (VMN) decreases body weight by reducing feeding and increasing energy expenditure (EE) in animals on standard laboratory chow. Animals have divergent responses to high-fat diet (HFD) exposure, with some developing obesity and others remaining lean. In the current study, we tested the hypothesis that BDNF in the VMN reduces HFD-induced obesity. Seventy-two 10-week old rats were allowed HFD ad libitum for 8 weeks and then prepared with bilateral VMN cannulae. Animals were then divided into tertiles based on their fat mass rank: high, intermediate, and low (H, I, and L). Each group was further divided into two subgroups: BDNF (1 µg) or control (artificial cerebrospinal fluid, aCSF); they were then injected every other day for 20 days according to subgroup. Energy intake, body weight, and body composition were measured. Other metabolic indexes were measured before and after treatment. In parallel, another 12 rats were fed control diet (CD), VMN-cannulated, and injected with aCSF. HFD exposure induced obesity in the H group, with a significant increase in energy intake, body weight, fat mass, liver size, and serum glucose, insulin, and leptin. BDNF significantly reduced body weight and fat mass in all phenotypes, while it reduced energy intake only in the I group. However, BDNF increased EE, spontaneous physical activity, and fat oxidation in the H group, suggesting that BDNF-induced EE elevation contributed to reduction of body weight and fat mass. Chronic VMN BDNF reduced insulin elevation and/or reversed hyperleptinemia. These data suggest that the VMN is an important site of action for BDNF reduction of HFD-induced obesity.

A biometrical approach for determining the effects of treatment with a chemotherapeutic agent upon heart weight in the mature rabbit.

Changes in heart weight as attributable to treatments involving a chemotherapeutic agent (CTA) were studied using adult rabbits. CTA was administered to each subject three times a week until sacrifice. Dose level per administration was held constant with respect to mg of CTA per kgm of body weight. The level of treatment for a given animals was then determined by the length of time the animal was in the treatment program prior to sacrifice. At sacrifice, variations in heart weight were evaluated relative to sex, initial body weight, relative change in body weight and level of treatment. Regression techniques were used in the analysis of data. This procedures allowed for differentiation between the direct effects and indirect effects of treatment. The direct effect was shown to cause a significant increment in heart weight. The indirect effect as related to loss body weight was shown to lead to a significant decrement in heart weight.