Hormonal, metabolic and morphologic studies of aged C57BL/6J obese mice.
Genetically obese mice (C57BL/6J-ob/ob), fed ad libitum, demonstrated a precipitous increase in the spontaneous death rate after 50 weeks. The first signs of morbidity were a ruffled hair coat and a progressive motor ataxia. Necropsy revealed that obese mice had pale and fatty livers, urolithiasis and grossly distended bladders. Microscopically, the hepatocellular changes observed in all aged obese mice included: a loss of orientation of hepatocytes, an enormous variability in the size of both hepatocytes and their nuclei, and an extensive deposition of both large and small lipid droplets, confirmed by an increase content of triacylglycerols. A subacute-to-chronic, multifocal, necrotizing hepatitis was also present. Kidneys from aged obese mice contained hypertrophied glomeruli and increased PAS-stained material. Tubular dilation with compaction of the tubular cells was also seen. There were no significant alterations in the microanatomy or mineralization of femurs from obese mice, yet there was a significant increase in plasma alkaline phosphatase activity. In obese mice at 62-63 weeks of age, hyperglycemia was present even in spite of hyperinsulinemia. Pituitary immunoreactive ACTH and its molar ratio to pituitary immunoreactive beta-endorphin were also increased in obese mice at this age. Even though the etiology of the decreased lifespan of genetically obese mice remains uncertain, the possibility is discussed that an overall defect in the central nervous system may be involved.
D000308:Adrenocortical Hyperfunction / Q000378:metabolism / Q000662:veterinary*; D000367:Age Factors; D000818:Animals; D001259:Ataxia / Q000662:veterinary; D001851:Bone Diseases, Metabolic / Q000662:veterinary; D001923:Brain Chemistry; D005234:Fatty Liver / Q000662:veterinary; D006946:Hyperinsulinism / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism*; D008820:Mice, Obese / Q000378:metabolism*; D012376:Rodent Diseases / Q000378:metabolism*; D014545:Urinary Calculi / Q000662:veterinary