Carcass and Liver Composition Following Acute Oxytetracycline Treatment of ob/ob Mice

Fully mature (24-week old) C57BL/6J ob/ob mice and their lean littermates received daily oxytetracycline injections (50 or 100 mg/kg) during a 10 day period. The effects of the drug on the glucose, IRI, corticosterone levels, and on hepatic and body composition of ad libitum fed obese mice were compared with those of food-restricted and ad libitum fed lean and obese control animals. When compared with food-restricted obese mice, drug treatment led to substantial reductions of serum glucose, serum IRI, carcass fat, and hepatic lipid content, while it increased lean body mass and liver glycogen concentration. Similarly, oxytetracycline decreased body weight, and serum glucose in lean mice, but the drug had no substantial effect on circulating IRI levels or on the lipid content of carcass. A significant increase in hepatic lipid was observed in drug-treated lean mice. No effects of the drug on basal corticosterone levels were noted in either phenotype. These data support previous findings showing the effectiveness of oxytetracycline to reverse many of the metabolic abnormalities of ob/ob mice. In addition, the present results suggest that the drug acts by independently altering abnormal metabolism in many target organs, including pancreas, adipose tissue, liver, and muscle, rather than by merely reducing circulating insulin levels or by generally increasing insulin sensitivity.