Weanling rats with electrolytic destruction of the ventromedial hypothalamic nuclei (VMN) develop elevated plasma triglyceride and insulin levels despite normal food intake. Triglyceride, insulin and adipose tissue lipoprotein lipase activity (LPL) were studied in VMN and sham-operated (control) rats fed 0, 6 or 25 per cent fat diets. On a 25 per cent fat diet, plasma from VMN rats exhibited the highest triglyceride levels, immobile lipoproteins with trailing from the pre-beta region to the origin on electrophoresis, and visible top particles in polyvinylpyrrolidone columns. On 6 per cent fat, triglyceride levels were lower than on the 25 per cent fat diet but remained greater than those of the controls; immobile lipoproteins and visible top particles were absent but trailing of lipoproteins from the pre-beta region to the origin was still evident on an electrophoretic strip. On a fat-free diet, VMN and control plasma triglycerides were identical but subsequent fasting for forty-eight hours produced elevated triglycerides in VMN rats. The diet-dependent alterations in triglycerides, lipoprotein electrophoretic patterns and polyvinylpyrrolidone columns indicated a combination of endogenous and exogenous hypertriglyceridemia.
LPL was increased in VMN rats on all diets but was decreased to levels similar to those of control animals by forty-eight hours of fasting. The exogenous increase in triglycerides which occurred despite the increased adipose tissue LPL was investigated. These studies failed to demonstrate the presence of LPL inhibitors, decreased release of LPL into the circulation or resistance of lipoproteins to hydrolysis but suggested an impaired ability of VMN tissue to take up circulating lipid.