Effects of ethyl-p-chlorophenoxyisobutyrate, clofibrate, on the plasma and red blood cell free fatty acids of the rat

Cenedella, Richard J.; Jarrell, J.; Saxe, L. H.

doi:10.1016/s0368-1319(68)80004-3

Cited by 33 publications

(13 citation statements)

References 10 publications

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“…The present studies confirm previous observations of a fall in serum glycerol, which probably results from inhibition of lipolysis (7,8). A similar decline in hepatic sn-glycerol-3-P has been reported and may be a consequence of the lower glycerol level or a result of changes in thyroid metabolism (14).…”

Section: Glycerol-i-sn-glycerol-3-p-dihydroxyacetone-supporting

confidence: 92%

“…However, the mechanism by which the drug reduces serum triglyceride is uncertain. Multiple potential modes of action have been suggested and include; an increased uptake of serum triglyceride by adipose tissue (6) ; a decrease in fatty acid release from adipose tissue (7) manifested by reduced serum free fatty acid levels (8); a reduction in the rate of hepatic triglyceride release (9)(10)(11)(12) ; and inhibition of hepatic fatty acid synthesis (13). Changes in the distribution of thyroid hormone also have been postulated as a mode of action for CPIB (14).…”

mentioning

confidence: 99%

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Inhibition of hepatic triglyceride formation by clofibrate

Adams¹,

Webb²,

Fallon³

1971

J. Clin. Invest.

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A B S T R A C T The effect of clofibrate (CPIB) on hepatic glycerolipid formation has been studied in vivo and in vitro in the rat. Feeding 0.25% CPIB in laboratory chow significantly reduced serum triglyceride levels by 6 hr and concomitantly decreased the rate of glycerol-4C incorporation into hepatic and serum glycerides, in vivo. These changes persisted for at least 14 days. A similar decrease in serum triglyceride and glycerol incorporation into hepatic glycerides was observed in rats fed high glucose diets containing 0.25% CPIB. Serum glycerol was reduced by feeding CPIB for 14 days. The formation of diglyceride and triglyceride from 14C-snglycerol-3-P by rat liver homogenates was inhibited by addition of 1-40 mm CPIB to the reaction mixture. These results suggest that CPIB reduces hepatic glycerolipid synthesis, possibly by inhibition of one or more reactions in the esterification of sn-glycerol-3-P. This change may account for the early fall in serum triglyceride. At later time periods, serum glycerol levels fall and in some experiments, hepatic triglyceride content increases. Therefore, it is likely that additional metabolic alterations may contribute to the sustained hypotriglyceridemic effects of CPIB.

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Section: Glycerol-i-sn-glycerol-3-p-dihydroxyacetone-supporting

confidence: 92%

mentioning

confidence: 99%

Inhibition of hepatic triglyceride formation by clofibrate

Adams¹,

Webb²,

Fallon³

1971

J. Clin. Invest.

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“…The dose of clofibrate conventionally given to rats (0.25 g/100 g chow) results in levels of CPIB in plasma about twice those that we (Table III) and others (23) have observed in man. These higher levels are associated with reduced concentrations of FFA (5,11) and glycerol (26). Reduced plasma levels of FFA could contribute to the hypolipemic effect of clofibrate in this species provided that the turnover rate of FFA in the presence of clofibrate does not rise in proportion to the decrease in FFA concentration.…”

Section: Results-mentioning

confidence: 93%

“…To determinie the recovery of CPIB from plasma, 2 ml of stock isooctanie-ethanol, coIntaining 100 nmol of CPIB, was added to 0.4 ml of plasma and the results were compared with those obtained with the usual extraction of another sample of the same plasma. CPIB was prepared by the alkaline hydrolysis procedure of Cenedella (5) and extracted by shaking together equal volumes (100 ml) of aqueous CPIB (4 mM) and isooctaneethanol and then discarding the aqueous phase. The extract was washed once with 5 ml 0.05% H2SO4.…”

Section: Methodsmentioning

confidence: 99%

“…It is especially effective in lowering serum triglyceride levels in endogenous hyperlipemias. Al-thouglh it has been suggested that clofibrate reduces serum triglycerides through effects on mobilization of free fatty acids (FFA) (4,5) or on transport of endogenous trigly ceride fatty acids (TGFA)1 (6)(7)(8)(9), its mechanism of action in man is unclear. WVe have approached these questions directly by quantifying the effects of clofibrate on the transport and the splanchnic nmetabolism of FFA in normotriglyceridenmic and hypertriglyceridemic human subjects under standardized conditions.…”

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confidence: 99%

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Mechanism of the Hypolipemic Effect of Clofibrate in Postabsorptive Man

Wolfe¹,

Kane²,

Havel³

et al. 1973

J. Clin. Invest.

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A B S T R A C T Splanchnic metabolism of triglycerides and other major substrates was studied in the postabsorptive state in normotriglyceridemic and hypertriglyceridemic human subjects wh}o received A g of clofibrate four times daily for 3 wNk. Transport in blood plasma of triglycerides produced in the splanchnic region was quantified by three methods: (a) measurement of the transsplanchnic gradient of '4C-labeled triglycerides during constant intravenous infusion of [1-"C]palmitate (b) chemical measurement of the transsplanchnic gradient in concenltration of triglycerides of very low density lipoproteins; and (c) determination of clearance of 14C-labeled triglycerides in extrasplanchnic tissues. The first method measures only triglycerides derived from free fatty acids and the last two measure total splanchnic production. In hypertriglyceridemic subjects treated with clofibrate, average rates of total splanchulic production of triglycerides and productioni from free fatty acids were the same as those of conmparable untreated subjects despite a consistent fall in plasma triglyceride levels. The hvpotriglyceridemic effect of the drug was therefore accompanied by improved disposal of triglycerides in extrasplanchnic tissues. In treated normotriglyceridemic subjects, unlike their untreated counterparts, total splanchnic production wvas significantly higlher than prodluction from free fatty acids.

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Effect of Drugs on Plasma Triglyceride Metabolism

Nikkilä

1972

Advances in Experimental Medicine and Biology

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Effects of ethyl-p-chlorophenoxyisobutyrate, clofibrate, on the plasma and red blood cell free fatty acids of the rat

Cited by 33 publications

References 10 publications

Inhibition of hepatic triglyceride formation by clofibrate

Inhibition of hepatic triglyceride formation by clofibrate

Mechanism of the Hypolipemic Effect of Clofibrate in Postabsorptive Man

Effect of Drugs on Plasma Triglyceride Metabolism

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