Developmental changes in adipose and muscle lipoprotein lipase activity in the atherosclerosis-prone JCR:LA-corpulent rat

Abstract

Objective: To characterize the developmental changes in adipose and muscle lipoprotein lipase (LPL) activity in the atherosclerosis-prone JCR:LA-corpulent rat, and to test the hypothesis that tissue-specific abnormalities in LPL activity precede the establishment of obesity.

Design: Lean (+/?) and obese cp/cp male JCR:LA rats were studied at 4, 5 and 8 weeks of age, that is at the onset of obesity, and at a time when obesity is well established. Assessment was made of plasma variables related to glucose and lipid metabolism and of LPL activity in several adipose depots, skeletal muscles and the heart.

Results: At week 4, body weights were identical in both genotypes and began to diverge at week 5. Eight-week-old cp/cp rats weighed 35% more than their lean counterparts. Perirenal and epididymal adipose depot weights were also identical in both genotypes at week 4 and began to increase in cp/cp rats at week 5, whereas the subcutaneous depot of 4-week-old cp/cp rats was slightly enlarged. At week 4, the cp/cp rats were hyperinsulinemic (5-fold), hyperleptinemic (30-fold) and hypertriglyceridemic (3-fold) compared to their lean counterparts, and their liver contained twice as much triglyceride. The 4-week-old cp/cp rats displayed 2-7-fold higher LPL specific activity in the various adipose depots compared to lean rats, and enzyme activity remained higher in obese than in lean rats at all subsequent ages. In contrast, LPL activity in the vastus lateralis, gastrocnemius and heart muscles of 4-week-old obese rats was approximately half that observed in lean animals.

Conclusion: Profound, persistent alterations in the tissue-specific modulation of LPL activity are established in the JCR:LA cp/cp rat prior to the development of frank obesity. The increase in adipose tissue LPL activity and its decrease in muscle tissues are likely to be related to the concomitant alterations in insulinemia and triglyceridemia, respectively. The pre-obesity, tissue-specific alterations in LPL activity may be considered as an integrated adaptation to increased lipid flux aimed at driving lipids toward storage sites and limiting their uptake by triglyceride-laden muscles.