Document Type
Thesis
Date of Award
1981
Abstract
The diabetes mouse (db/db) is a genetic mutant that displays hyperphagia, obesity, hyperglycemia, hypoactivity and hypothermia. In addition, hypothalamic norepinephrine (NE) is elevated in these mice, in comparison to lean littermates. Recent work has shown that central catecholamine depletion produced by intraventricular infusion of 6-hydroxydopamine (6-OHDA) in the db/db mouse results in significant weight loss and decreased blood glucose levels. The purpose of this study was to examine both long and short term effects of central NE depletion in db/db mice and to evaluate some of the behavioral and physiological factors that may contribute to weight loss following 6-OHDA lesions. Body weight, food intake, activity levels, body temperature, brain amine levels, blood glucose, adiposity and pancreatic islet cell morphology were assessed. In all animals treated with 6-OHDA, substantial telencephalic and hypothalamic NE reductions were induced. Telencephalic dopamine levels were also decreased. In groups allowed to survive for 120 days after surgery (long term survival groups), vehicle treated db/db mice exhibited weight gains until approximately 90 days after surgery. However, from 90-120 days post surgery, vehicle treated db/db mice lost weight and experienced a gradual deterioration in health, while 6-OHDA db/db mice maintained a stable weight during this period. Carcass composition of 6-OHDA and vehicle treated db/db mice appeared to parallel weight loss in these older mice. Body fat was comparable in the two groups, while the severely hyperglycemic db/db vehicle group showed a significant reduction in lean body mass in comparison with 6-OHDA treated db/db mice. The short term effects of 6-OHDA lesions were examined within 64 days after surgery in db/db mice. Diabetes mice with 6-OHDA lesions were compared with an ad libitum fed db/db vehicle group and with a food restricted db/db vehicle group (VFR). Both 6-OHDA treatment and food restriction produced weight loss in db/db mice. Furthermore, 6-OHDA lesions suppressed food intake in diabetes mice. Blood glucose and body fat were reduced in both 6-OHDA and VFR db/db groups. However, in order to achieve reductions in body weight, body fat and blood glucose comparable to those achieved by 6-OHDA treated mice, VFR mice required food restriction equivalent to the food intake of lean mice. When pair-fed with 6-OHDA treated mice, VFR mice continued to gain weight. 6-OHDA treatment, but not food restriction, reduced activity levels and body temperature in db/db mice. Homozygous lean 6-OHDA treated mice also showed reductions in both activity and body temperature. The results indicate that although 6-OHDA treatment produces decrements in food intake, the 6-OHDA lesion is not the functional equivalent of starvation. Terminal stage db/db vehicle-treated mice and 6-0HDAtreated db/db mice differed in both behavior and in carcass composition. The 6-OHDA treated mice lost weight despite decreases in activity .and body temperature, suggesting that in addition to decreased food intake, some as yet unidentified metabolic change accounts for 6-OHDA induced weight loss.
Recommended Citation
Pelleymounter, Mary Ann, "Factors Contributing to Weight Loss Induced by Intraventricular 6-Hydroxydopamine Lesions in Diabetes (db/db) Mice." (1981). All ETDs from UAB. 6913.
https://digitalcommons.library.uab.edu/etd-collection/6913
Comments
MA - Master of Arts; ProQuest publication number 31751833