Elaine Wat

Dietary Krill Oil Supplementation Reduces Hepatic Steatosis, Glycemia, and Hypercholesterolemia in High-Fat-Fed Mice

Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids rather than in triglycerides. In the present study, we investigated the effects of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk + 0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4) HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO supplementation caused a significant reduction in liver wt (i.e., hepatomegaly) and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/- 5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by 20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34 +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These results demonstrate that dietary KO is effective in improving metabolic parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic value in patients with the metabolic syndrome and/or nonalcoholic fatty liver disease.

Dietary phospholipids, hepatic lipid metabolism and cardiovascular disease

Purpose of review An increasing number of studies in experimental animals suggest that dietary phospholipids might be of benefit in the treatment of fatty liver disease. This raises the possibility that synthetic or naturally occurring phospholipid isolates could be used as hepatoprotective nutraceuticals or functional foods. The aim of the present article is to review published data describing the beneficial effects of dietary phospholipids on hepatic lipid metabolism and their potential to affect atherosclerosis and cardiovascular disease. Recent findings Consistent results have been obtained supporting the concept that phospholipid from various sources (i.e., soybean, safflower, egg and fish roe) can reduce liver lipid levels. The primary site of action for this effect appears to be in the intestinal lumen, where dietary phospholipids are able to interfere with neutral sterol absorption. Results have also been obtained suggesting that dietary phospholipids can stimulate bile acid and cholesterol secretion. Additional work suggests that dietary phospholipids can have a beneficial effect on plasma lipid and lipoprotein levels. Summary The concept of using naturally occurring compounds such as phospholipid to treat or prevent hepatic steatosis is very attractive. Controlled human trials are, however, required to verify the efficacy of this approach. It is also important that additional research be conducted to determine the extent to which certain phospholipids have the ability to increase plasma HDL levels and potentially affect the onset or development of cardiovascular disease.

Dietary phospholipids and intestinal cholesterol absorption.

Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the ability of PLs to inhibit cholesterol absorption is of therapeutic benefit.

Dietary phospholipid-rich dairy milk extract reduces hepatomegaly, hepatic steatosis and hyperlipidemia in mice fed a high-fat diet

Recent studies have suggested that milk and certain dairy food components have the potential to protect against cardiovascular disease. In order to determine whether the addition of milk-derived phospholipids to the diet results in an improvement in metabolic and cardiovascular risk factors, we studied four groups (n=10) of C57BL/6 mice that were fed: (1) a normal non-purified diet (N); (2) the normal non-purified diet supplemented with phospholipid-rich dairy milk extract (PLRDME, 2.5% by wt) (NPL); (3) a high-fat semi-purified diet (HF) containing 21% butterfat+0.15% cholesterol by wt; or (4) HF supplemented with 2.5% by wt PLRDME (HFPL). Dietary PLRDME supplementation did not have a significant effect on metabolic parameters in mice fed the N diet. In contrast, in high-fat fed mice, PLRDME caused a significant decrease in: (a) liver wt (1.57+/-0.06 g vs. 1.20+/-0.04 g, P<0.001), (b) total liver lipid (255+/-22 mg vs. 127+/-13 mg, P<0.001, (c) liver triglyceride (TG) and total cholesterol (TC) 236+/-25 micromol/g vs. 130+/-8 micromol/g (P<0.01), 40+/-7 micromol/g vs. 21+/-2 micromol/g (P<0.05), respectively); and serum lipids (TG: 1.4+/-0.1 mmol/L vs. 1.1+/-0.1 mmol/L, P=0.01; TC: 4.6+/-0.2 mmol/L vs. 3.6+/-0.2 mmol/L, P<0.001; and PL: 3.3+/-0.1 mmol/L vs. 2.6+/-0.1 mmol/L, P<0.01). These data indicate that dietary PLRDME has a beneficial effect on hepatomegaly, hepatic steatosis and elevated serum lipid levels in mice fed a high-fat diet, providing evidence that PLRDME might be of therapeutic value in human subjects as a hepatoprotective or cardioprotective nutraceutical.

Reduction in intestinal cholesterol absorption by various food components: Mechanisms and implications

A number of different food components are known to reduce plasma and LDL-cholesterol levels by affecting intestinal cholesterol absorption. They include: soluble fibers, phytosterols, saponins, phospholipids, soy protein and stearic acid. These compounds inhibit cholesterol absorption by affecting cholesterol solubilization in the intestinal lumen, interfering with diffusion of luminal cholesterol to the gut epithelium and/or inhibiting molecular mechanisms responsible for cholesterol uptake by the enterocyte. Cholesterol content of intestinal chylomicrons is subsequently reduced, less cholesterol is transported to the liver within chylomicron remnants, hepatic LDL-receptor activity is increased and plasma levels of LDL-cholesterol are decreased. Reduced hepatic VLDL production and less conversion of VLDL to LDL also contribute to lower LDL levels. Certain food components may also affect intestinal bile acid metabolism. Further investigation of the way in which these functional ingredients affect intestinal lipid metabolism will facilitate their use and application as cardiovascular nutraceuticals.

Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids

BackgroundMilk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. We have speculated that this might be due to reduced intestinal cholesterol uptake.MethodsMice were given a high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented with 1.2% by wt PL from cows milk. Two milk PL preparations were investigated: a) a PL-rich dairy milk extract (PLRDME), and b) a commercially-available milk PL concentrate (PC-700). Intestinal cholesterol uptake was assessed by measuring fecal and hepatic radioactivity after intragastric administration of [14C]cholesterol and [3H]sitostanol. Fecal and hepatic lipids were measured enzymatically and by ESI-MS/MS.ResultsBoth PL preparations led to significant decreases in total liver cholesterol and triglyceride (-20% to -60%, P < 0.05). Hepatic accumulation of intragastrically-administered [14C]cholesterol was significantly less (-30% to -60%, P < 0.05) and fecal excretion of [14C]cholesterol and unlabeled cholesterol was significantly higher in PL-supplemented mice (+15% to +30%, P < 0.05). Liver cholesterol and triglyceride levels were positively correlated with hepatic accumulation of intragastrically-administered [14C]cholesterol (P < 0.001) and negatively correlated with fecal excretion of [14C]cholesterol (P < 0.05). Increased PL and ceramide levels in the diet of mice supplemented with milk PL were associated with significantly higher levels of fecal PL and ceramide excretion, but reduced levels of hepatic PL and ceramide, specifically, phosphatidylcholine (-21%, P < 0.05) and monohexosylceramide (-33%, P < 0.01).ConclusionThese results indicate that milk PL extracts reduce hepatic accumulation of intestinal cholesterol and increase fecal cholesterol excretion when given to mice fed a high-fat diet.

Hydrogenated phosphatidylcholine supplementation reduces hepatic lipid levels in mice fed a high-fat diet.

The ability of the fatty acid composition of dietary phosphatidylcholine (PC) to affect hepatic lipid levels was investigated in C57BL/6 mice (n=8-10 per group) by feeding: (1) a high-fat semi-purified diet (HF), (2) HF diet supplemented with 1.25 wt% soy PC (SPC), (3) HF with 1.25 wt% hydrogenated soy PC (SPCH), (4) HF with 1.25 wt% egg PC (EPC), and (5) HF with 1.25 wt% hydrogenated egg PC (EPCH). The polyunsaturated fatty acid content (C18:2+C18:3+C20:4) of soy, egg and hydrogenated PC was 70%, 20% and 0%, respectively. Total liver lipid was significantly lower in SPCH and EPCH vs. HF (8.7 ± 0.1 and 8.5 ± 0.5 vs. 11.8 ± 0.6g/100, P<0.05), but not in SPC or EPC. SPCH and EPCH had significantly lower levels of hepatic cholesterol (-52% and -53% vs. HF, respectively). Bioactive lipids (i.e., sphingomyelin and ceramide) were also lower in the liver of SPCH and EPCH rather than in SPC or EPC. Hepatic expression of genes controlling fatty acid synthesis and catabolism were not significantly affected by dietary PC. However, hepatic expression of HMGCR, LDLR and SREBP2 was higher and that of ABCA1, ABCG5 and ABCG8 was reduced in SPCH and EPCH vs. HF. These results demonstrate that hydrogenated PC supplementation reduces hepatic lipid levels in mice fed a high-fat diet supporting the concept that the ability of dietary PC to lower hepatic lipid levels is not due to its content of polyunsaturated fatty acids.

Dietary krill oil significantly reduces hepatic steatosis, glycaemia and hypercholesterolaemia in high-fat-fed mice

Dietary krill oil (KO), rich in n-3 fatty acids associated with phospholipid, is extracted from Antarctic krill (Euphausia superba). Taken as a dietary supplement, it is believed to have important anti-inflammatory and cardioprotective properties.. In order to investigate the effects of KO on lipid and glucose metabolism, the present study was carried out in mice fed a high-fat diet supplemented with different doses of KO. Male C57BL/6 mice were fed a high-fat (HF) diet (w/w; 21% butterfat, 0.15% cholesterol) supplemented with 0, 1.25, 2.5 or 5% (w/w) dietary KO. Animals (six to ten per group) were killed after 8 weeks. Livers were analysed for lipid content and serum samples for lipids, glucose and adiponectin. Dietary KO supplementation caused a significant reduction in liver weight (i.e. hepatomegaly) and total liver fat (i.e. hepatic steatosis) as a result of a dose-dependent reduction in hepatic TAG ( 35 (SE 6) %, 47 (SE 4) % and 51 (SE 5) % with KO supplementation of 1.25, 2.5 and 5.0% respectively; P<0.001) and cholesterol (55 (SE 5) %, 66 (SE 3) % and 71 (SE 3) % with KO supplementation of 1.25, 2.5 and 5.0% respectively; P<0.001).