Effects of Chlorpromazine on Lipolysis in Brown and White Adipose Tissues of Cold-Exposed Rats

Abstract

Abstract-Effectsof chlorpromazine (CPZ) on lipolysis in brown (interscapular: IBAT) and white (epididymal: EWAT) adipose tissues in cold-exposed rats were studied in vitro. Adult male Wistar-Imamichi rats were exposed to 4°C for 1 (acute cold-exposed) or 30 (cold-acclimated) days. The spontaneous free fatty acid (FFA) release from interscapular brown adipose tissue (IBAT) of control rats, was three fold higher than epididymal white adipose tissue (EWAT). FFA release from the EWAT of acute cold-exposed rats was significantly higher than that of control rats. After cold ac climation, FFA release from IBAT increased up to three times that of the control level. CPZ (10-', 10-3 M) suppressed the elevated lipolytic activity in IBAT of cold acclimated rats. However CPZ had no effect on FFA release from EWAT or IBAT in all other groups. A single intravenous administration of 10 mg/kg 6-hydroxy dopamine (6-OHDA) produced a marked decrease in the concentration of noradrenaline and dopamine in MAT and EWAT of cold-acclimated rats. FFA release from IBAT in 6-OHDA treated, cold-acclimated rats decreased to 50 % of untreated, cold-acclimated rats. A further decrease in lipolytic activity in the IBAT of 6-OHDA treated, cold-acclimated rats was produced following CPZ treatment. CPZ also depressed the lipolysis stimulated by the added noradrenaline (3 x 10-5 M). These results suggest that the effect of CPZ on the lipolysis in the IBAT from cold-acclimated rats is mediated by a modification of sympathetic activity.It is now generally accepted that the sympathetic nervous system plays an important role in the mobilization of free fatty acids (FFA) from adipose tissues.In particular, brown adipose tissue which is hypertrophied in cold-acclimated animals (1, 2) is intensively in nervated with sympathetic nerves in comparison to the white adipose tissue (3). The function of brown adipose tissue is to produce heat responding to the cold-stimulated release of noradrenaline from sympathetic nerve endings within the tissue (4-6). Free fatty acids following the augmented lipolysis may serve as essential substrates for thermogenesis in cold environments (7). A number of agents have been shown to inhibit lipolysis by inter fering with steps in the lipolytic process. Previous work has shown that chlorpromazine (CPZ) inhibits noradrenaline induced in vitro lipolysis in the rat epididymal fat (8). In vivo, CPZ also increases plasma FFA level (9, 10).We previously found that removal of interscapular brown adipose tissue (IBAT) po tentiated the hypothermia induced by CPZ injection in the cold-acclimated rats (11). This finding indicated that IBAT is involved in the CPZ induced hypothermia in the cold acclimated rat. Therefore, the following experiments were undertaken to determine the effects of CPZ on the stimulated lipolysis of adipose tissue which occurs during the cold exposure.Effects of chlorpromazine on the in vitro lipolysis were studied in the brown and white adipose tissues from control, acute cold-exposed and cold-acclimated rats. MAT...

Influence of Cold Exposure on Dopamine Content in Rat Brown Adipose Tissue

“…This increase in BAT DA content lasts for at least 30 days, if rats are maintained at a low temperature; thus, while in a first period cold induces opposite effects on BAT DA and NE, after 30 days BAT content of both amines is increased. No significant increase in BAT DA in adult rats was found following 24 hours exposure to 4'C (Uchida 1979).…”

Immunohistochemical evidence for the existence of a dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) in brown adipose tissue of pigs.

“…Since the effect of dopamine was similar to that of forskolin, a stimulator of adenylate cyclase, Maxwell et al (22) have suggested the presence of D1 receptors on brown adipocytes. Evidence for a dopaminergic role in BAT physiology is further supported by the detection of dopamine in BAT (23)(24)(25) (27) but also dopamine receptors are involved in regulation of BAT. In adult humans, significant levels of dopamine have been detected in plasma (28), and in newborn human subjects the urine level of dopamine is twice the level of norepinephrine (29). The origin of the plasma dopamine (28) and the source of dopamine that may be involved in regulation of BAT are poorly understood.…”