Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms.

Abstract

The effects of adenosine deaminase and of pertussis toxin on hormonal regulation of lipolysis were investigated in isolated human fat cells. Adenosine deaminase (1.6 5tg/ml) caused a twoto threefold increase in cyclic AMP, which was associated with an increase in glycerol release averaging 150-200% above basal levels. Clonidine, N'-phenylisopropyladenosine, prostaglandin E2, and insulin caused a dose-dependent inhibition of glycerol release in the presence of adenosine deaminase.Pretreatment of adipocytes with pertussis toxin (5 ,ug/ml) for 180 min resulted in a five-to sevenfold increase in cyclic AMP. Glycerol release was almost maximal and isoproterenol caused either no further increase or only a marginal additional increase of lipolysis after pretreatment with pertussis toxin, whereas cyclic AMP levels were 500 times higher than in controls. The effects of antilipolytic agents known to affect lipolysis by inhibition of adenylate cyclase activity, i.e., clonidine, N6-phenylisopropyladenosine, and prostaglandin E2, were impaired. In contrast, the antilipolytic action of insulin was preserved in adipocytes pretreated with pertussis toxin. As in controls, the peptide hormone had no detectable effect on cyclic AMP after pertussis toxin treatment.The findings support the view that the antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. In addition, the results demonstrate that, upon relief of endogenous inhibition, human fat cell lipolysis proceeds at considerable (adenosine deaminase) or almost maximal (pertussis toxin) rates. A certain degree of inhibition, therefore, appears to be necessary for human fat cell lipolysis to be susceptible for hormonal activation.

Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis

“…This was also observed when adenosine was removed, which could artificially leak out of fat cells and inhibit the basal rate [20]. Furthermore, maximum noradrenaline-induced lipolysis was higher in carriers of the A-allele than those with GG.…”

“…In the insulin experiments 10 −3 mol/l of 8-bromo cyclic AMP (a phosphodiesterase sensitive cyclic AMP analogue) was added to the buffer. In the clonidine and insulin experiments 1 U/ml of adenosine deaminase (ADA) was added to remove any traces of adenosine in the incubation medium which might otherwise interfere with basal lipolysis and the antilipolytic effect of the used agents [20]. Each agent was added in increasing concentrations (10 −15 -10 −3 mol/l), depending on the drug.…”

Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome

“…19 Results from multiple sources show that addition of the adenosine deaminase to the medium increases the basal, but not the stimulated lipolysis. 20 Interestingly, addition of adenosine deaminase was also found not to reduce variability of catecholamine stimulated lipolysis. 21 As we did not choose to use the isolated adipocytes, we decided not to add adenosine deaminase into the medium.…”

Lipid metabolism in the elderly

“…In humans, the release of free fatty acids is primarily regulated by inhibitory modulators, such as insulin (Kather et al, 1985). Aging is associated with reduced sensitivity to the anti-lipolytic effect of insulin in isolated adipocytes (Bolinder et al, 1983).…”