Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity.
We examined the effect of dietary fat on the response to 3-hydroxybutyrate (3-OHB) and insulin infused chronically into the third ventricle in three strains of rats with differing susceptibility to obesity induced by a high-fat diet: Osborne-Mendel rats are most susceptible; Sprague-Dawley-rats are intermediate; and S 5B/Pl rats are most resistant. Ten days after implantation of cannulas into the third ventricle, rats were fed either a low-fat diet or a high-fat diet for 14 days. On day 7, osmotic minipumps were attached to the ventricular cannulas. 3-OHB infusions (3.6 mumol/24 h) reduced food intake and body weight in Sprague-Dawley and Osborne-Mendel rats eating either diet. The dietary fat-resistant S 5B/Pl rats did not respond to the intracerebroventricular infusion of 3-OHB. The infusion of insulin (10 mU/24 h) lowered food intake and body weight in animals eating the low-fat (high-carbohydrate) diet but not in animals eating the high-fat diet. Diet profoundly affects the response to intracerebroventricular infusions of insulin but is without effect on the response to 3-OHB.
Arase
K
K
Department of Medicine, School of Medicine, University of Southern California, Los Angeles 90033.
Fisler
J S
JS
Shargill
N S
NS
York
D A
DA
Bray
G A
GA
D020155:3-Hydroxybutyric Acid; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D004041:Dietary Fats; D004195:Disease Models, Animal; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D004041:Dietary Fats; D006885:Hydroxybutyrates; D007328:Insulin; D020155:3-Hydroxybutyric Acid