Brain lipoprotein lipase is responsive to nutritional and hormonal modulation

Abstract

Functional lipoprotein lipase activity was recently described in rat brain. The present study was performed to further characterize the biologic significance of brain lipoprotein lipase (heparin releasable component) and elucidate regulatory factors. Comparative studies were performed on tissue (brain, adipose, and heart) heparin releasable lipoprotein lipase in the fasted and diabetic (streptozotocin 100 mg/kg BW IP) rat. Both fasting (96 hours) and diabetes (ten days) significantly decreased brain (cortical) ( P < .05) and adipose (epididymal fat pad) ( P < .001) lipoprotein lipase activity. In contrast, heart muscle enzyme activity was significantly increased ( P < .001) in response to fasting and diabetes. Refeeding (Purina chow 96 hours) and insulin replacement (96 hours) reversed these changes in tissue lipoprotein lipase consequent to fasting and diabetes, respectively. There was a positive correlation between the changes in serum insulin concentration and adipose lipoprotein lipase, but there was no correlation between this parameter and brain or heart lipoprotein lipase. In addition, although T 3 therapy normalized the low T 3 state associated with both fasting and diabetes, it had no effect on the enzyme activity in the studied tissues. However, subsequent studies demonstrated that hypothyroidism (2 weeks post thyroidectomy) significantly decreased brain lipoprotein lipase activity ( P < .001) and increased both the adipose ( P < .025) and heart ( P < .025) enzyme activity. T 3 replacement ( 0.8 μg 100 BW/d for 1 week ) reversed the effects of hypothyroidism. However, the relationship between brain enzyme activity and serum T 3 was nonlinear as hyperthyroidism tended to reduce brain LPL activity. These studies demonstrate that rat cortex heparin releasable lipoprotein lipase is responsive to fasting, diabetes, and hypothyroidism. Although both insulin and T 3 reversed, respectively, the effects of diabetes and hypothyroidism on cortex LPL, confirmation of direct hormone effects on enzyme activity must await future in vitro studies. The brain and adipose LPL response to fasting and diabetes was concordant, whereas the effect of hypothyroidism on the respective enzymatic responses was discordant. This study does indicate that cortical lipoprotein lipase could play an important role in brain lipid metabolism.