Key result
Clofibrate is evaluated for modulating plasma free fatty acids and lipid levels in preclinical models.
Why the study?
The mechanisms by which clofibrate reduces circulating lipid levels were not fully defined. Specifically, it was unknown whether clofibrate affects resting and stimulated plasma free fatty acid levels or experimentally induced rises in circulating cholesterol, phospholipids, and total esterified fatty acids.
Answers are grounded in this paper and cite their sources.
May inform mechanistic studies of clofibrate; leaves open clinical relevance in humans.
It is well established that clofibrate (ethyl-a-p-chlorophenoxy-a-methyl-propionate, Atromid-S) reduces circulating lipid levels although the mechanisms of this effect have not yet been fully defined.One possible explanation is that clofibrate alters the process of lipid synthesis from acetate precursor, which in turn may depend on its rate of production by the metabolism of long-chain fatty acids.It is known that chlorophenoxyisobutyric acid (CPIB), which is the active form of clofibrate in vivo, is strongly bound to plasma albumin at sites concerned with the transport of other anions-for example, plasma free fatty acids (Thorp, 1963).It might be expected that a reduction of circulating levels of free fatty acids would lead to a lower availability of acetate for hepatic lipid synthesis.Experiments in vitro have shown that CPIB will reduce the rate of fatty acid release from epididymal fat pads incubated in plasma.It was concluded that such an effect followed competition for acidic binding sites and might well contribute to the overall hypolipaemic effects in vivo (Barrett, 1966a).At the same time it was found that CPIB had little effect on lipolysis in vitro stimulated by adrenaline.In other experiments it has been shown that repeated injections of adrenaline, each causing an increase in fat mobilization, will in time produce an increase in the circulating levels of plasma lipoproteins in dogs (Shafrir, Sussman & Steinberg, 1960).Subsequent studies have demon- strated, however, that experimentally induced hyperlipoproteinaemia is not necessarily dependent on increased rates of fatty acid mobilization (Barrett, 1966b).The present experiments were undertaken to determine whether or not clofibrate affected (a) the level of plasma free fatty acids at rest and under conditions of stimulation and (b) experimentally induced rises in circulating cholesterol, phospholipids and total esterified fatty acids. METHODSThe animals used in this study were male albino rats (200-240 g) from a specific pathogen free colony, and female beagles (10-12 kg), both species being bred at Alderley Park.The details
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A. M. Barrett (1968) studied Experimentally induced hyperlipoproteinaemia and hormone-induced lipid changes. Clofibrate (Atromid-S / chlorophenoxyisobutyric acid) was evaluated on Plasma free fatty acids at rest and under stimulation, and experimentally induced rises in circulating cholesterol, phospholipids, and total esterified fatty acids. Clofibrate was evaluated in male albino rats (200-240 g) and female beagles (10-12 kg) for effects on plasma free fatty acids and lipid levels, though results are truncated from the abstract.
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