Lipoprotein lipase of adipose tissue and skeletal muscle in human obesity: Response to glucose and to semistarvation

Obesity is frequently associated with elevated plasma levels of triglyceride and very low density lipoproteins (VLDL). It is possible that this could be at least partly attributed to defective removal of triglycerides from circulation. Therefore, we studied the response of tissue lipoprotein lipase (LPL) activity to stimulation by glucose and to suppression by caloric deficiency in subjects with simple obesity and in nonobese controls. A five-hour intravenous infusion of glucose increased the LPL activity in both adipose tissue and skeletal muscle. The average rise was 2.5-fold in nonobese subjects but only 1.8-fold in obese patients (p < 0.05). The decrease of response was similar in obese subjects with and in those without hypertriglyceridemia suggesting that the change was due to obesity as such. During feeding a 400 cal diet for 7 days the LPL activity of obese subjects fell by an average of 50% in adipose tissue and by 40% in skeletal muscle. The decreases are smaller than previously found in nonobese human subjects in a similar experiment. The magnitude of decrease of LPL activity in both tissues was positively correlated with initial enzyme activity but was not influenced by serum triglyceride level. During starvation the HDL cholesterol levels were reduced the change being positively related to simultaneous decreases of LPL activity in adipose tissue and in skeletal muscle. It is concluded that the metabolic regulation of tissue LPL activity (of the heparin-releasable pool) is abnormal in obesity. This may be related to insulin resistance of obese people and it may explain why obese people are basically more prone to develop hypertriglyceridemia than lean ones. The resistance of LPL to caloric restriction in obese subjects could bear on difficulties in reducing the adipose tissue mass.