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Author(s): L Hodson; L Bhatia; E Scorletti; D E Smith; N C Jackson; F Shojaee-Moradie; M Umpleby; P C Calder; C D Byrne Correction to: European Journal of Clinical Nutrition [...]

Objective: To examine, in free-living adults eating self-selected diets, the effects on plasma cholesterol of substituting saturated fat rich foods with either n-6 polyunsaturated or monounsaturated fat rich foods while at the same time adhering to a total fat intake of 30-33% of dietary energy. Design: Two randomised crossover trials. Setting: General community. Subjects: Volunteer sample of healthy free-living nutrition students at the University of Otago. Trial I, n =29; and trial II, n = 42. Interventions: In trials I and II participants were asked to follow for 22 1 weeks a diet high in saturated fat yet with a total fat content that conformed to nutrition recommendations (30-33% energy). During the 21/2 week comparison diet, saturated fat rich foods were replaced with foods rich in n-6 polyunsaturated fats (trial I) whereas in trial II the replacement foods were rich in monounsaturated fats. Participants were asked to maintain a total fat intake of 30-33% of energy on all diets. Main outcome measures: Energy and nutrient intakes, plasma triglyceride fatty acids, and plasma cholesterol. Results: When replacing saturated fat with either n-6 polyunsaturated fat or monounsaturated fat, total fat intakes decreased by 2.9% energy and 5.1% energy, respectively. Replacing saturated fat with n-6 polyunsaturated fat (trial I) lowered plasma total cholesterol by 19% [from 4.87 (0.88) to 3.94 (0.92) mmol/l, mean (s.d.)], low density lipoprotein cholesterol by 22% [from 2.87 (0.75) to 2.24 (0.67) mmol/l], and high density lipoprotein cholesterol by 14% [from 1.39 (0.36) to 1.19 (0.34) mmol/l], whereas replacing saturated fat with monounsaturated fat (trial II) decreased total cholesterol by 12%, low density lipoprotein cholesterol by 15%, and high density lipoprotein cholesterol by 4%, respectively. The change in the ratio of total to high density lipoprotein cholesterol was similar during trial I and trial II. Conclusions: Young adults are very responsive to dietary-induced changes in plasma cholesterol even when an isocaloric replacement of saturated fat with n-6 polyunsaturated or monounsaturated fat is not achieved. Replacing saturated fat with either n-6 polyunsaturated or monounsaturated fat is equally efficacious at reducing the total to high density lipoprotein cholesterol ratio. Sponsorship: University of Otago, Meadow Lea Ltd. Descriptors: young adults; plasma triglyceride fatty acids; saturated fat; monounsaturated fat; n-6 polyunsaturated fat; plasma cholesterol, Introduction There is widespread agreement that decreasing saturated fat intake is the cornerstone of dietary recommendations to reduce blood cholesterol-mediated risk of cardiovascular disease (Grandy & Denke, 1990; NCEP, 1991). [...]

Correction to: European Journal of Clinical Nutrition (2017) 71, 973-979; doi:10.1038/ejcn.2017.9; published online 15 March 2017 Updated online 16 August 2017: This article was originally published under a standard EJCN license, but has now been made available under a CC BY 4.0 license. The PDF andHTML versions of the paper have been modified accordingly., Author(s): L Hodson, L Bhatia, E Scorletti, D E Smith, N C Jackson, F Shojaee-Moradie, M Umpleby, P C Calder, C D Byrne Author Affiliations: Correction to: European Journal of [...]

Most tumours have an aberrantly activated lipid metabolism 1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation 3 . This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.

Background/objectives: Although assumed, it remains unclear that fatty acid (FA) biomarkers of n-3 long-chain PUFA reflect wide ranges of intake. However, to be utilised as biomarkers, to predict dietary intake, dose-response curves that cover a spectrum of intakes are required. The aim of the study was to investigate whether the FA composition of plasma phosphatidylcholine (PC) is a sensitive biomarker of n-3 FAs from fish oil, across a range of supplementation doses, and alpha-linolenic acid (ALA) supplementation, in young, healthy women., Subjects/methods: A total of 303 young women were randomised to intakes ranging between 0.33 and 4.50 g EPA+DHA/day from fish oil (not all doses used in each year) or flaxseed oil (5.90-6.60 g/d) daily for 14 days in a series of trials, over 5 years. Fasting blood was collected at baseline (day 0) and day 14 and plasma PC FA composition, total and HDL-cholesterol and triglyceride concentrations measured., Results: Fourteen days supplementation with fish oil significantly (P < 0.01) increased, in a dose-dependent fashion, plasma PC EPA, DPA and DHA at all doses except 1 and 3 mL/day. For the combined group of women who consumed any fish oil there was a 16% (P < 0.01) decrease in plasma triacylglycerol concentrations after 14 days supplementation. Flaxseed oil supplementation for 14 day resulted in significant (P < 0.01) increases in ALA, EPA and DPA, whilst DHA remained unchanged., Conclusion: Our data demonstrate plasma PC is a sensitive biomarker of n-3 FA intake and reflects changes within 14 days across a range of intakes.

Intramyocellular lipid (IMCL) is of particular metabolic interest, but despite many proton magnetic resonance spectroscopy ( 1 H MRS) studies reporting IMCL content measured by the methylene (CH 2 ) resonance signal, little is known about its composition. Here we validated IMCL CH 3 :CH 2 ratio as a compositional marker using 1 H MRS at short echo time, and investigated IMCL content and composition during a 28-hour fast in 24 healthy males. Increases in IMCL CH 2 relative to the creatine and phosphocreatine resonance (Cr) at 3.0 ppm (an internal standard) correlated with circulating free fatty acid (FA) concentrations, supporting the concept of increased FA influx into IMCL. Significant decreases in IMCL CH 3 :CH 2 ratio indicated a less unsaturated IMCL pool after fasting, and this compositional change related inversely to IMCL baseline composition, suggesting a selective efflux of unsaturated shorter-chain FA from the IMCL pool. This novel in vivo evidence reveals IMCL turnover during extended fasting, consistent with the concept of a flexible, responsive myocellular lipid store. There were also differences between soleus and tibialis anterior in basal IMCL composition and in response to fasting. We discuss the potential of this marker for providing insights into normal physiology and mechanisms of disease.

We tested whether lowering of blood pressure (BP) on the dietary approaches to stop hypertension (DASH) diet was associated with changes in peripheral vascular function: endothelial function, assessed by flow-mediated vasodilatation (FMD) of the brachial artery, and subcutaneous adipose tissue blood flow (ATBF). We also assessed effects on heart rate variability (HRV) as a measure of autonomic control of the heart. We allocated 27 men and women to DASH diet and control groups. We measured FMD, ATBF and HRV on fasting and after ingestion of 75 g glucose, before and after 30 days on dietary intervention, aiming for weight maintenance. The control group did not change their diet. The DASH-diet group complied with the diet as shown by significant reductions in systolic (P<0.001) and diastolic (P=0.005) BP, and in plasma C-reactive protein (P<0.01), LDL-cholesterol (P<0.01) and apolipoprotein B (P=0.001), a novel finding. Body weight changed by <1 kg. There were no changes in the control group. We found no changes in FMD, or in ATBF, in the DASH-diet group, although heart rate fell (P<0.05). Glucose and insulin concentrations did not change. In this small-scale study, the DASH diet lowered BP independently of peripheral mechanisms.