Plasma free fatty acids and serum insulin in subjects feeding at 12-hour intervals; effects of methionyl growth hormone and of acipimox, an inhibitor of lipolysis

In normal men, plasma free fatty acids (FFA) are influenced by feeding and by fasting; in addition, iv infusions of methionyl growth hormone (met-GH), so far performed during morning hours, induce an FFA rise that can be blocked by acipimox (ACX), a nicotinic acid analogue. The aims of the present study were to evaluate, in the absence of food interferences, the following aspects: i) Fasting FFA, glycerol, and insulin (IRI) in the morning and in the evening, and their response to met-GH ii) The effect of ACX and of a sustained release ACX formulation (ACX-SR) on fasting and met-GH induced lipolysis and on IRI levels. In a double blind study, 6 normal men received 50% cal at 09:30 h and 50% at 21:30 h; during placebo administrations FFA, glycerol, and IRI levels were lower at 06:30 h than at 18:30 h, and an iv met-GH infusion (160 ng/kg/min lasting 180 min) had a similar effect on FFA and on glycerol at 06:30 h and at 18:30 h. ACX-SR, administered at 21:30 h and 09:30 h, lowered FFA and glycerol in the morning as well as in the evening, and prevented met-GH induced lipolysis in the morning, but not in the evening. In another single blind study, 5 normal men received the last meal at 22:00 h, ACX 250 mg or placebo at 07:00 h and at 11:00 h and a met-GH infusion (80 ng/kg/min lasting 240 min) at 09:00 h; one month later they received the last meal at 07:30 h, ACX 250 mg or placebo at 16:30 h and at 20:30 h, and an identical met-GH infusion at 18:30 h. Again, ACX lowered FFA in the morning and in the evening, and prevented the lipolytic effect of met-GH in the morning, not in the evening. These data indicate that met-GH induces lipolysis in man, increasing both FFA and glycerol levels, and that ACX blocks these effects. In addition, in the absence of food interferences, FFA, glycerol, and IRI levels are different in the morning and in the evening. The fact that both ACX and ACX-SR prevented met-GH induced lipolysis in the morning, not in the evening, can be due to a peculiarity of ACX or to a different sensitivity of the adipose tissue to met-GH and/or other lipolytic agents (i.e. catecholamines, not evaluated in this study) in different moments of the day.