Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats.
In outbred Sprague-Dawley rats, about one-half develop diet-induced obesity (DIO) on a diet relatively high in fat and energy (HE diet). The rest are diet resistant (DR), gaining weight and fat at the same rate as chow-fed controls. Here we selectively bred for high (DIO) and low (DR) weight gainers after 2 wk on HE diet. By the F5 generation, both male and female inbred DIO rats gained > 90% more weight than inbred DR rats on HE diets. Even on low-fat chow diet, DIO males were 31% and females were 22% heavier than their respective DR rats. Full metabolic characterization in male rats showed that weight-matched, chow-fed DIO-prone rats had similar energy intakes and feed efficiency [body weight (kg0.75)/energy intake (kcal)] but 44% more carcass fat than comparable DR-prone rats. Their basal plasma insulin and glucose levels in the fed state were 70 and 14% higher, respectively. But, when fasted, DIO-prone oral glucose tolerance results were comparable to DR-prone rats. Chow-fed DIO-prone males also had 42% greater 24-h urine norepinephrine levels than DR-prone males. During 2 wk on HE diet, DIO rats ate 25% more, gained 115% more weight, had 36% more carcass fat, and were 42% more feed efficient than comparable DR rats. Fasted HE diet-fed DIO rats developed frank glucose intolerance during a glucose tolerance test with 55 and 158% greater insulin and glucose areas under the curve, respectively. Thus the DIO and DR traits in the outbred Sprague-Dawley population appear to be due to a polygenic pattern of inheritance.
Levin
B E
BE
Neurology Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey 07018, USA.
Dunn-Meynell
A A
AA
Balkan
B
B
Keesey
R E
RE
D000822:Animal Husbandry; D000818:Animals; D002940:Circadian Rhythm; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000652:urine; D009765:Obesity / Q000209:etiology* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics* / Q000378:metabolism; D015430:Weight Gain
D005947:Glucose; D009638:Norepinephrine