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Nutrition and Disease

Lipid Metabolism in Diet-Induced Obese Rabbits Is Similar to That of Obese Humans^1,2

³ Metabolism Unit, Shriners Hospital for Children, and Departments of ⁴ Surgery and ⁵ Anesthesiology, University of Texas Medical Branch, Galveston, TX 77550

^* To whom correspondence should be addressed. E-mail: xzhang{at}utmb.edu.

Whereas diet-induced obese rabbits have been used to study various aspects of obesity, alterations of lipid metabolism in this model have not been clarified. This study aimed to compare plasma nonesterified fatty acid (NEFA) and triglyceride (TG) kinetics in obese and lean rabbits by means of U-¹³C₁₆-palmitate infusion. Young female rabbits consumed either a high-fat diet (49% energy from fat) ad libitum to develop obesity (n = 6) or a normal diet (7.9% energy from fat) as lean control (n = 5). After 10 wk of feeding, the body weight of obese rabbits (5.33 ± 0.05 kg) was greater (P < 0.001) than that of lean rabbits (3.89 ± 0.07 kg). The obese rabbits had higher concentrations of plasma NEFA and TG and a greater rate of fatty acid (FA) turnover. Whereas the fractional secretion rates of hepatic TG did not differ, 100% of hepatic secretory TG was synthesized from plasma NEFA in the lean rabbits compared to 59% in the obese rabbits (P < 0.001). In the lean rabbits, hepatic lipase-mediated hydrolysis of lipoprotein TG did not contribute to the FA pool for synthesis of secretory TG, consistent with the naturally occurring deficit in hepatic lipase in this species. We conclude that lipid metabolism in diet-induced obese rabbits is similar to that in obese humans. The deficiency in hepatic lipase in rabbits simplifies the quantitation of hepatic lipid kinetics.