Induction of lipid droplet accumulation in cardiac muscle cells of guinea pigs and mice: An analysis of the effects of reserpine and fasting

Abstract

Reserpine has been demonstrated in previous studies to induce the accumulation of lipid droplets in ventricular cardiac muscle cells of bats and this effect has been attributed to mediation by the sympathetic nervous system. The present study was done to evaluate the species specificity of this action of the drug. Reserpine caused lipid droplet accumulation in cardiocytes of guinea pigs and mice. However, in contrast to the action of the drug in bats, this action of reserpine in guinea pigs and mice could not be antagonized by chemical sympathectomy with 6-hydroxydopamine or by treatment of animals with phenoxybenzamine, atropine or hexamethonium. Like reserpine, fasting for as little as 24 hours induced lipid droplet accumulation in cardiocytes of guinea pigs and mice. This effect also could not be prevented by treatment with 6-hydroxydopamine indicating that the sympathetic nervous system was not involved in its mediation. Force-feeding guinea pigs given reserpine prevented the accumulation of lipid droplets normally induced by this drug. It is concluded that the lipid droplet accumulation in the hearts of guinea pigs that follows administration of reserpine is not due to a direct cardiotoxicity of the drug but is secondary to the failure of drug-treated animals to eat. Since the autonomic nervous system appears to mediate reserpine's cardiotoxicity in bats, the species difference revealed by these experiments probably results from an underlying physiological difference in the nervous systems of these animals.Reserpine has been shown to induce lipid droplet accumulation (LDA) in cardiocytes of bats (Hagopian e t al., '72). This change is antagonized by pretreatment of bats with 6-hydroxydopamine (6-HD1, phenoxybenzamine, or atropine (Hagopian e t al., '73; Hagopian e t al., '75). The change is also seen during the first 1-4 hours following arousal of bats from hibernation (Hagopian e t al., '73b). Moreover, lipid droplets accumulate in the heart when bats are injected with exogenous norepinephrine (NE) or the tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA) (Nunez e t al., '75; Hagopian e t al., '73b). A hypothesis has been put forward ascribing LDA to sympathetic neural activity (Nunez e t al., '75).The present experiments were done t o determine if LDA of the kind induced in bats by reserpine is a species-specific phenomenon, or whether other mammals also develop the change. Guinea pigs and mice were used as experimental animals and LDA was assessed histochemically and biochemically. Although reserpine does induce LDA in these other animals, the change does not seem to be a primary one and the data derived from the guinea pigs and mice is not comparable to that from bats. In guinea pigs and mice starvation for as little as 24 hours causes LDA and it is likely that LDA following administration of reserpine is secondary to these animals' failure to eat. MATERIALS A N D METHODS AnimalsAdult male Hartley guinea pigs (300-350 gm) and Swiss white mice (10-35 gm) were used in this study. All...

Fat accumulation in the rat heart during fasting

“…While there is an extensive literature on the biochemical effects of starvation on the heart, there are very few descriptions of the morphological changes and only two brief and incomplete references to work on the rat could be found (Gimeno et al, 1973;Krustev et nl., 1975). The most recent morphological work is by Iacovitti and Gershon (1978) who investigated cardiac LDA in guinea-pigs and mice which were fasted and deprived of water for up to 72 hr. Only the left ventricles were examined and sex and age were not stated.…”

“…Any attempt to describe lipid distribution from an examination of a single chamber or by averaging results for the whole heart could be misleading. Iacovitti and Gershon (1978) examined only the L ventricles of guinea-pigs and mice. The distribution within the chambers was not described.…”