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Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We investigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different cell lines: HepG2 (human hepatoblastoma–derived cell line), Huh7 (human hepatocellular carcinoma cell line) and McA-RH7777 (McA, rat hepatocellular carcinoma cell line). Cells were treated for 48 h with fatty acids (0 or 200 μM), glucose (5 mM or 11 mM) and fructose (0 mM, 2 mM or 8 mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (p < 0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11 mM glucose plus fatty acids (p = 0.004, fatty acid × glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (p < 0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (p = 0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (p < 0.001 for fatty acid × insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (p < 0.001 insulin × cell type interaction). Hence, glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH. [ABSTRACT FROM AUTHOR]

Trans fatty acids (TFA) from industrial sources [i.e. partially hydrogenated vegetable oil (PHVO)] have been associated with several chronic human diseases, especially coronary heart disease (CHD). The possible contribution of individual TFA to overall CHD risk remains largely unknown. The objective of the present study was to investigate the effects of 2 major trans 18:1 isomers, trans-9 18:1 [elaidic acid (EA)] and trans-11 18:1 [vaccenic acid (VA}] on plasma lipid biomarkers of CHD risk. Thirty-two male Golden Syrian hamsters were randomly assigned to 1 of 4 dietary treatments: 1) control 'Western' diet; 2) PHVO supplement; 3) EA supplement; and 41 VA supplement. Fat supplements were incorporated into the respective treatment diets at 2.5 g/100 g of diet. Compared with the control diet, the PHVO diet increased the plasma ratios of total:HDL-cholesterol and nonHDL:HDL-cholesterol by 17 and 23%, respectively. In contrast, these values decreased by 27 and 46% after the EA treatment and 8 and 14% after the VA treatment, respectively, indicating an improvement (reduction) in CHD risk. With regard to liver lipids, the EA diet reduced the content of (n-3) and (n-6) PUFA relative to the other treatments, suggesting an inhibition of enzymes common to the 2 biosynthesis pathways. Overall, results demonstrate that the hypercholesterolemic effects of PHVO are not dependent on the presence of EA or VA and that other bioactive components in PHVO must be responsible for its associated adverse health effects.

The nutritional environment encountered during fetal life is strongly implicated as a determinant of lifelong metabolic capacity and risk of disease. Pregnant rats were fed a control or low-protein (LP) diet, targeted to early (LPE), mid-(LPM), or late (LPL) pregnancy, or throughout gestation (LPA). The offspring were studied at 1, 9, and 18 mo of age. All LP-exposed groups had similar plasma triglyceride, cholesterol, glucose, and insulin concentrations to those of controls at 1 and 9 mo of age, but by 18 mo there was evidence of LP-programmed hypertri-glyceridemia and insulin resistance. All LP-exposed groups exhibited histological evidence of hepatic steatosis and were found to have two- to threefold more hepatic triglyceride than control animals. These phenotypic changes were accompanied by age-related changes in mRNA and protein expression of the transcription factors SREBP-1c, ChREBP, PPAR[gamma], and PPAR[alpha] and their respective downstream target genes ACC1, FAS, L-PK, and MCAD. At 9 mo of age, the LP groups exhibited suppression of the SREBP-1c-related lipogenic pathway but between 9 and 18 mo underwent a switch to increased lipogenic capacity with a lower expression of PPAR[gamma] and MCAD, consistent with reduced lipid oxidation. The findings indicate that prenatal protein restriction programs development of a metabolic syndrome-like phenotype that develops only with senescence. The data implicate altered expression of SREBP-1c and ChREBP as key mediators of the programmed phenotype, but the basis of the switch in metabolic status that occurred between 9 and 18 mo of age is, as yet, unidentified. pregnancy; lipids; transcription factors; insulin resistance; metabolic syndrome doi:10.1152/ajpendo.00605.2006.

Butter, which is naturally enriched in cis-9, trans-11 conjugated linoleic acid (rumenic acid; RA) and vaccenic acid (VA), has been shown to be an effective anticarcinogen in studies with animal models; however, there has been no examination of the effects of a naturally derived source of VA and RA on atherosclerosis-related biomarkers. The current study was designed to determine the effect of a diet containing VA/RA-enriched butter on plasma lipoproteins and tissue fatty acid profiles in cholesterol-fed hamsters. Male Golden Syrian hamsters were fed diets containing 0.2% cholesterol and 20% added fat as: 1) Control, 20% standard butter (CT); 2) 5% standard butter + 15% VA/RA-enriched butter (EB); 3) 15% standard butter + 5% partially-hydrogenated vegetable oil (VO). After 4 wk, plasma lipoproteins were isolated, cholesterol quantified, and tissue fatty acid profiles determined. Tissue concentrations of VA and RA were increased by consumption of the EB diet compared with both the CT and VO diets, whereas the VO diet increased their concentration compared with the CT diet only. Total and LDL cholesterol concentrations were significantly reduced in hamsters fed EB and VO compared with CT, whereas VLDL cholesterol concentrations were reduced in hamsters fed EB compared with those fed CT and VO. HDL cholesterol concentrations did not differ among treatments. The ratio of potentially atherogenic lipoproteins [VLDL + intermediate density lipoproteins (IDL) + LDL] to antiatherogenic HDL was significantly lower in hamsters fed VA/RA-enriched butter (0.60) than in those fed either control diet (1.70) or the diet containing partially hydrogenated vegetable oil (1.04). Thus, increasing the VA/RA concentration of butter results in a plasma lipoprotein cholesterol profile that is associated with a reduced risk of atherosclerosis. J. Nutr. 135: 1934-1939, 2005. KEY WORDS: * conjugated linoleic acid * vaccenic acid * plasma cholesterol * functional food * human health

The present paper reviews the evidence as to whether patients on lipid-lowering drugs should restrict dietary SFA intake. Premature mortality from atherosclerotic CVD has fallen dramatically in many high-income countries. This appears to be due to a combination of improved treatment following a cardiovascular event and reduced risk factors, including LDL-cholesterol. Whether this reduction is due to changes in dietary habits, or the increasing availability of highly potent cholesterol-reducing drugs remains to be firmly established. While reducing dietary SFA intake has been the cornerstone of public health nutrition policy for several decades, the efficacy of such dietary changes has been challenged in recent years. While there remains a lack of consensus in the literature, there is an emerging view that dietary advice should be specifically modified to emphasise replacing SFA with PUFA in the diet rather than carbohydrate. The advice to moderate dietary SFA intake given to the general population is usually also given to those individuals at high risk of CVD who are prescribed lipid-lowering drugs. There is limited evidence to suggest that any potential benefit of such a diet on LDL-cholesterol may be offset by a concurrent decrease in HDL-cholesterol. However, as diets rich in SFA are frequently energy-dense, and rich in red and processed meat (potential risk factors for CVD in themselves), it would seem prudent to continue to advise patients on lipid-lowering drugs to maintain a low-fat diet. [ABSTRACT FROM AUTHOR]

Nutrition during pregnancy can impact on the susceptibility of the offspring to CVD. Postnatal consumption of trans-fatty acids (TFA), associated with partially hydrogenated vegetable oil (PHVO), increases the risk of atherosclerosis, whereas evidence for those TFA associated with ruminant-derived dairy products and meat remain equivocal. In this study, we investigate the impact of maternal consumption of dietary PHVO (P) and ruminant milk fat (R) on the development of atherosclerosis in their offspring, using the transgenic apoE 3 Leiden mouse. Dams were fed either chow (C) or one of three high-fat diets: a diet reflecting the SFA content of a ‘Western’ diet (W) or one enriched with either P or R. Diets were fed during either pregnancy alone or pregnancy and lactation. Weaned offspring were then transferred to an atherogenic diet for 12 weeks. Atherosclerosis was assessed as lipid staining in cross-sections of the aorta. There was a significant effect of maternal diet during pregnancy on development of atherosclerosis (P=0·013) in the offspring with those born of mothers fed R or P during pregnancy displaying smaller lesions that those fed C or W. This was not associated with changes in total or lipoprotein cholesterol. Continuing to feed P during lactation increased atherosclerosis compared with that seen in offspring of dams fed P only during pregnancy (P<0·001). No such effect was seen in those from mothers fed R (P=0·596) or W (P=901). We conclude that dietary TFA have differing effects on cardiovascular risk at different stages of the lifecycle. [ABSTRACT FROM AUTHOR]

Global demand for meat and dairy products has increased dramatically in recent decades and, through a combination of global population growth, increased lifespan and improved economic prosperity in the developing world will inevitably continue to increase. The predicted increases in livestock production will put a potentially unsustainable burden on global resources, including land for production of crops required for animal feed and fresh water. Furthermore, animal production itself is associated with greenhouse gas production, which may speed up global warming and thereby impact on our ability to produce food. There is, therefore, an urgent need to find methods to improve the sustainability of livestock production. This review will consider various options for improving the sustainability of livestock production with particular emphasis on finding ways to replace conventional crops as sources of animal feeds. Alternatives, such as currently underutilised crops (grown on a marginal land) and insects, reared on substrates not suitable for direct consumption by farm animals, represent possible solutions. Coupled with a moderation of excessive meat consumption in wealthier countries, such strategies may secure the long-term sustainability of meat and milk production and mitigate against the adverse health effects of excessive intake. [ABSTRACT FROM PUBLISHER]