REGULATION OF HORMONE-SENSITIVE LIPASE DURING FASTING

Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysi s. The activity of HSL is thought to be primarily regulated by phospho rylation-dephosphorylation reactions. Although FFA levels are elevated during fasting, it has been difficult to demonstrate an increase in H SL activity with fasting. The current studies were undertaken to explo re directly the regulation of HSL expression in adipose tissue in the rat during fasting. Rats were fasted for periods up to 5 days and HSL activity, HSL immunoreactive protein, and HSL mRNA levels were measure d both in intact epididymal adipose tissue and in isolated adipose cel ls. Fasting caused a progressive decline in total body weight and the weight of epididymal fat pads, whereas adipose cell size decreased sim ilar to 50% after 2 days of fasting. Serum FFA levels approximately do ubled within 1 day of fasting and remained elevated thereafter. Basal lipolysis, measured as glycerol release, did not increase until 2 days of fasting. HSL activity remained relatively unchanged until 3 days o f fasting when it was increased twofold after 3-5 days of fasting. Lik ewise, HSL immunoreactive protein and HSL mRNA levels increased twofol d after 3-5 days of fasting. Thus HSL activity appears to be regulated by pretranslational mechanisms during prolonged fasting. However, inc reases in FFA flux during short-term fasting appear to involve either posttranslational control of HSL or the regulation of other enzymes.