Relationship of organ lipoprotein lipase activity and ketonuria to hypertriglyceridemia in starved and streptozocin-induced diabetic rats.

Abstract

Although lipoprotein lipase (LPL) is believed to be rate limiting in the catabolism of triglyceride-rich lipoproteins, LPL activity has not correlated with plasma triglyceride concentrations in experimental rat diabetes. To gather more information about this enzyme system in diabetes, LPL activities were measured in representative tissues from control and streptozocin-induced diabetic rats fed fat-free chow and in 48-h-starved animals. The DNA content of each tissue was determined so that LPL activity could be expressed in a way that was unaffected by tissue wasting. Diabetic animals lost approximately 20% of their body mass. Adipose tissue and soleus muscle cell masses were reduced, and there was marked fat atrophy at necropsy. Adipose tissue LPL was decreased in both starved and diabetic animals, whereas skeletal muscle activities were variably affected. Lipase content and distribution among the individual organs were calculated with published data for rat carcass composition. In diabetic rats, total LPL (adipose tissue, muscle, and parenchymal organs) was reduced by nearly two-thirds so that skeletal muscle became the predominant source of LPL. Ketonuria was less frequent in diabetic than in starved rats (P less than .018) despite their severe wasting. Serum triglyceride concentrations were higher in ketonuric than nonketonuric diabetic animals, and severe hypertriglyceridemia was seen exclusively in heavily ketonuric animals. These observations together with published information suggest that plasma triglyceride concentrations in the rat model are determined by a complex interplay between very-low-density lipoprotein synthesis, the capacity of the LPL removal system, properties of the lipoprotein substrate, and other unidentified factors.