Reduction of Plasma Lipids, Lipoproteins, and Apoproteins by Dietary Fish Oils in Patients with Hypertriglyceridemia

Abstract

Dietary fish oils, which are rich in omega-3 fatty acids, have been reported to reduce plasma lipid levels in normolipidemic subjects. We examined the effects of fish oil in 20 hypertriglyceridemic patients: 10 with Type IIb hyperlipidemia and 10 with Type V. These patients were put on three diets differing primarily in fatty acid composition and fat content. The control diet contained a fatty acid mixture typical of a low-fat therapeutic diet (ratio of polyunsaturated to saturated fat, 1.4), the fish-oil diet contained omega-3 fatty acids, and the vegetable-oil diet was rich in the omega-6 fatty acid, linoleic acid. Each diet was followed for four weeks. In the Type IIb group, the fish-oil diet led to decreases in both plasma cholesterol (-27 per cent) and triglyceride (-64 per cent), as compared with the control diet. Very-low-density lipoproteins (VLDLs) were also reduced markedly. The vegetable-oil diet had much less effect. With fish oil, the Type V group had marked decreases in total cholesterol and triglyceride levels (-45 and -79 per cent, respectively). VLDL levels were dramatically lowered, as were apoprotein E levels. The vegetable-oil diet (unlike the fish-oil diet) produced a rapid and significant rise in plasma triglyceride levels. We conclude that fish oils and fish may be useful components of diets for the treatment of hypertriglyceridemia.

Effects of Supplemented Diacylglycerol Rich in Docosahexaenoic Acid on Serum Triacylglycerol in a Diet-Induced Hyperlipidemic Model of Rats Are Essentially Equivalent to Those of Triacylglycerol Rich in Docosahexaenoic Acid

“…Many studies have shown that feeding fish oil decreases the serum level of TG, and the mechanism of TG-lowering by fish oil appears to involve inhibition of VLDL secretion and TG synthesis. 1,4,23,24) The mechanisms governing n-3 fatty acid-mediated changes in lipid metabolism are thought to be partially mediated by the enhancement of peroxisome proliferator-activated receptor (PPAR) a. 25) Manipulation of the fatty acid composition of hepatic lipids by the feeding of fish oil has been shown to induce peroxisomal b-oxidation.…”

“…4,5) The hypotriglyceridemic effect of fish oils has been recognized in humans as well as animals of different species. [6][7][8] The component in fish oil responsible for lowering TG is considered to be principally EPA, not DHA.…”

Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.

“…Unsaturated fatty acids induce peroxisomal proliferation and lower blood triglyceride levels (1)(2)(3). Similar effects are evoked by a number of man-made compounds which are either considered for therapy of hyperlipidemia-e.g., clofibric acid, nafenopin, WY-14,643, or sulfur-substituted fatty acids-or are in use as industrial plasticizers (4)(5)(6).…”

Peroxisome Proliferator-activated Receptor α Inhibits Hepatic S14 Gene Transcription

“…Dietary polyunsaturated fatty acids (PUFA), 1 particularly highly unsaturated n Ϫ 3 PUFA, have a strong suppressive effect on hepatic lipogenesis and triglyceride synthesis leading to a decline in plasma triglycerides (1)(2)(3)(4)(5)(6)(7). The suppression of hepatic lipogenesis is due, at least in part, to an inhibition of transcription of several genes encoding proteins involved in both lipogenesis and glycolysis, including fatty acid synthase, stearoyl-CoA desaturase, L-type pyruvate kinase, and the S14 protein (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

“…The suppression of hepatic lipogenesis is due, at least in part, to an inhibition of transcription of several genes encoding proteins involved in both lipogenesis and glycolysis, including fatty acid synthase, stearoyl-CoA desaturase, L-type pyruvate kinase, and the S14 protein (1)(2)(3)(4)(5)(6)(7)(8)(9).…”