Is increased basal lipolysis in adipose tissue of fasted-refed rats related to cyclic-AMP-dependent mechanisms?

Abstract

The possible contribution of the cyclic AMP/protein kinase system to the enhanced basal lipolytic activity of rat adipose tissue in vitro after fasting and refeeding a carbohydrate-rich diet was investigated. 1 After 120 h of fasting/48 h of refeeding, the basal lipolytic rate was fourfold above normal, and the protein kinase activity ratio was significantly elevated. However, basal adenylate cyclase activity was not significantly different from normal, and basal cyclic AMP levels were unchanged despite an increased (+40%) low-Kmphosphodiesterase activity. 2 Insulin (500 μ/ml) stimulated (50%) low-Km, but not high-Kmphosphodiesterase activity in normal adipose tissue, but had no further stimulatory effect on the elevated low-Kmphosphodiesterase activity in the fasted-refed tissue. At the same concentration, insulin completely blocked enhanced basal lipolysis in the refed state and caused a small transient decrease of the cyclic AMP level (-16%) and of the protein kinase activity ratio (-10%), whereas it did not significantly influence any of the three latter indices in the normal tissue. Although adenosine (0.1 mM), like insulin, completely blocked enhanced lipolysis in the refed tissue, it did not lower tissue cyclic AMP or the protein kinase activity ratio. 3 After 72 h of fasting/72h of refeeding, the basal lipolytic activity of the adipose tissue was enhanced threefold above normal. However, the tissue cyclic AMP level and the protein kinase activity ratio were not different from those of normal tissue. 4 Lipolytic activity in homogenates from fasted-refed tissue previously exposed to epinephrine was twofold higher than in homogenates from the untreated tissue. It corresponded to the epinephrine-stimulated lipolytic rate of the ‘intact’ tissue and was accompanied by a drastic rise of the tissue cyclic AMP level and of the protein kinase activity ratio. In contrast, the pronounced inhibitory effect of insulin on enhanced basal lipolysis of refed tissue did not persist in homogenates of the same tissue preincubated with this hormone. These results reveal a number of discrepancies that are difficult to reconcile with an obvious and simple cyclic-AMP-dependent activation of basal lipolysis in the refed state. Furthermore, they suggest that the antilipolytic effect of insulin on fasted-refed-adipose tissue is unlikely to solely mediated by the cyclic AMP/protein kinase system.