Abstract-The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition, the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and postprandial lipid profile and on responsiveness to the dietary intervention was established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35 kg/m 2 , triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein cholesterol [HDL-C] Ͻ1.1 mmol/l, and percent low density lipoprotein [LDL]-3 Ͼ40% total LDL) completed a randomized placebo-controlled crossover trial of fish oil (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive oil) capsules with the 6-week treatment arms separated by a 12-week washout period. In addition to fasting blood samples, at the end of each intervention arm, a postprandial assessment of lipid metabolism was carried out. Fish oil supplementation resulted in a reduction in fasting TG level of 35% (PϽ0.001), in postprandial TG response of 26% (TG area under the curve, PϽ0.001), and in percent LDL-3 of 26% (PϽ0.05). However, no change in HDL-C levels was evident (Pϭ0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers (Pϭ0.035). The apoE genotype also had a striking impact on lipid responses to fish oil intervention. Individuals with an apoE2 allele displayed a marked reduction in postprandial incremental TG response (TG incremental area under the curve, Pϭ0.023) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers. In apoE4 individuals, a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident. Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment.

Responsible Research and Innovation (RRI) has recently emerged as a new framework for science and technology governance. The concept articulates the need for mutual exchange by which societal actors become responsive to each other early on in the process of innovation, with a view to facilitate ethically acceptable and sustainable innovation. There is relatively limited evidence to explore the extent to which the process of research and innovation under the terms of RRI is realised in practice, particularly in the context of food and health research. Although research to date has been examining innovation from the point of view of inputs and outputs—R&D funding and patents—we propose to examine the cognitive framing of innovation that shapes decisions of those who constitute a part of the innovation chain.\ud This paper explores how the concept of innovation is understood and used in policy implementation, with a particular focus upon ‘food and health’ science and research policy and funding. Our analysis is based on 55 interviews of various actors engaged in research funding decision-making across eight European countries. Three themes emerged from the analysis: concept of innovation; conditions for innovation; and drivers of innovation; through these themes, the cognitive framing was drawn out. The cognitive framing suggests that innovation in the food and health domain is perceived to be focused on biosciences and marketable applications to the neglect of social sciences and broader public interest; that the ‘‘innovation network” is primarily viewed as centred around scientific/technical and industrial actors; and that the demand-pull dynamic is relevant to innovation in the area of food and health, despite having been relegated in contemporary thinking and policies around innovation. These findings point to the inadequate consideration of the normative issues — how problems are to be defined and addressed — among national research funders in the food and health domain, and indicate a gap between the ideas of innovation under the terms of RRI and innovation as conceptualised by those involved in its\ud governance

Summary Adipocytes isolated from cachectic mice bearing the MAC 16 tumour showed over a 3-fold increase in lipolytic response to both low concentrations of isoprenaline and a tumour-derived lipid mobilizing factor (LMF). This was reflected by an enhanced stimulation of adenylate cyclase in plasma membrane fractions of adipocytes in the presence of both factors. There was no up-regulation of adenylate cyclase in response to forskolin, suggesting that the effect arose from a change in receptor number or G-protein expression. Immunoblotting of adipocyte membranes from mice bearing the MAC16 tumour showed an increased expression of Gαs up to 10% weight loss and a reciprocal decrease in Gα. There was also an increased expression of Gαs and a decrease in Gα in adipose tissue from a patient with cancer-associated weight loss compared with a non-cachectic cancer patient. The changes in G-protein expression were also seen in adipose tissue of normal mice administered pure LMF as well as in 3T3L1 adipocytes in vitro. The changes in G-protein expression induced by LMF were attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). This suggests that this tumour-derived lipolytic factor acts to sensitize adipose tissue to lipolytic stimuli, and that this effect is attenuated by EPA, which is known to preserve adipose tissue in cancer cachexia.

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© 2015 British Nutrition Foundation.Europe recognises the need for technological innovation along with the importance of bridging the gap between science and society. The European Commission has developed a strategy to foster public engagement and a sustained two-way dialogue between science and civil society, and has set up a framework for Responsible Research and Innovation. The EU-funded project INPROFOOD aimed to find new ways to establish dialogue and mutual learning among stakeholders meant to inform subsequent work and future initiatives towards Responsible Research and Innovation. More specifically, INPROFOOD aimed to: (1) increase understanding of the landscapes of food and health innovation research programming; (2) adapt, test and evaluate the application of different stakeholder engagement methods to the area of food and health innovation research programming, which included European Awareness Scenario Workshops, PlayDecide games and an Open Space conference; and (3) to develop an action plan to progress towards Responsible Research and Innovation in this domain. The latter entailed a so-called Mobilisation and Mutual Learning Action Plan, which lays down a concrete framework for inclusive stakeholder involvement at different stages of the research and innovation process, with tangible key actions in five priority areas

Induction of lipolysis in murine white adipocytes by a tumour lipid‐mobilising factor (LMF) was associated with stimulation of adenylate cyclase in adipocyte plasma membrane preparations. Induction of lipolysis was attenuated by the adenylate cyclase inhibitor MDL12330A and the protein kinase A inhibitor H8, suggesting that cAMP was the intracellular mediator of induction. The effect of LMF on adenylate cyclase was responsive to GTP, with low concentrations (0.1 μM) causing stimulation and high concentrations (10 μM) causing inhibition, suggesting the involvement of both stimulatory (Gs) and inhibitory (Gi) guanine nucleotide‐binding proteins. At a concentration of 10 μM, propranolol non‐competitively reduced the induction of lipolysis by LMF. Thus, lipolysis in white adipose tissue during the process of cancer cachexia is mediated by a tumour factor which stimulates cAMP production, possibly through a β‐adrenergic receptor. Int. J. Cancer 80:444–447, 1999. © 1999 Wiley‐Liss, Inc.

OBJECTIVE: To investigate the associations between indices of adiposity and cardiovascular risk factors in individuals with an atherogenic lipoprotein phenotype (ALP). SUBJECTS: Fifty-®ve men, aged 34 ± 69 y, body mass index (BMI) 22 ± 35 kgam 2 , with an ALP lipid pro®le (triglycerides (TG) 1.5 ± 4.0 mmolal, HDL`l.l mmolal; %LDL-3 b 40% total LDL). DESIGN: Each participant provided a fasting blood sample and underwent an 8 h postprandial assessment and had anthropometric measurements taken. OUTCOME MEASURES: BMI, waist circumference (W), waist-to-hip ratio (WaH), sum of skinfolds (SSK), fasting and postprandial concentrations of glucose, insulin and plasma lipids, post-heparin lipase activity, and apoE genotype. RESULTS: The expected positive associations between BMI, W and SSK and fasting and postprandial insulin were observed (r 0.42 ± 0.65). Little association between glucose responses and any measures of adiposity was evident. Unexpectedly, there were no positive associations between measures of central adiposity (W and WaH) and fasting and postprandial TG responses, with a trend towards negative associations in this study group (TG AUC vs W, r À À0.23, P 0.097; TG IAUC vs WaH, r À À0.26, P 0.068). Subgroup analysis indicated that lack of a positive association between central adiposity and postprandial TG values was more evident in those with one E4 allele (r À À0.42, P 0.077) relative to non-E4 carriers (r À À0.16, P 0.430). The expected positive associations between insulin and TG responses were not observed (r À À0.03 toÀ À0.36). CONCLUSION: In this ALP group the expected positive association between TG responses and a centralized distribution of body fat was not observed, particularly in individuals with an apoE4 genotype. Our ®ndings are not in line with the view that there is a clear causal relationship between insulin resistance and the lipid abnormalities associated with ALP.

We sought to test the hypothesis that dietary longchain n-3 PUFA (LC n-3 PUFA) in fish oil stimulate the gene expression of lipoprotein lipase (LPL) in human adipose tissue (AT). In a randomized, double blind, placebo-controlled, cross-over study, 51 male subjects expressing an atherogenic lipoprotein phenotype (ALP) had their diets supplemented with fish oil for 6 weeks. As we previously reported for this group, supplementation with LC n-3 PUFA produced a decrease in fasting plasma triglyceride (TG) ( ؊ 35%, P Ͻ 0.05), attenuation of the postprandial TG response (area and incremental area under the curve; AUC and IAUC, P Ͻ 0.05), and a decrease in small, dense LDL. The present study extended these observations by showing that these changes were accompanied by a marked increase in the concentration of LPL mRNA in adipose tissue (AT-LPL mRNA, ؉ 55%, P ‫؍‬ 0.003) and post-heparin LPL activity (PH-LPL, ؉ 31%, P ‫؍‬ 0.036). There was also evidence of an association between LPL gene expression and polymorphism in the apolipoprotein E gene.We conclude that the favorable influence of dietary n-3 PUFA on the ALP may be mediated, in part, through an increase in the plasma activity and gene expression of lipoprotein lipase in human adipose tissue.