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Background: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS.Objective: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS.Design: A free-living, single-blinded dietary intervention study.Subjects and Methods: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined.Results: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men.Conclusion: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles. [ABSTRACT FROM AUTHOR]

Objective: High-fat diet (HFD)-induced adipose tissue inflammation is a critical feature of diet-induced insulin resistance (IR); however, the contribution of interleukin-1 receptor I (IL-1RI)-mediated signals to this phenotype has not been defined. We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by attenuating adipose tissue inflammation.Research Design and Methods: Glucose homeostasis was monitored in chow- and HFD-fed wild-type (WT) and IL-1RI(-/-) mice by glucose tolerance and insulin tolerance tests. Macrophage recruitment and cytokine signature of adipose tissue macrophages was evaluated. Insulin sensitivity and cytokine secretion from adipose explants was quantified. Cytokine secretion and adipocyte insulin sensitivity was measured in cocultures of WT or IL-1RI(-/-) macrophages with 3T3L1 adipocytes. Synergistic effects of IL-1β with tumor necrosis factor (TNF)-α on inflammation was monitored in WT and IL-1RI(-/-) bone-marrow macrophages and adipose explants.Results: Lean and obese IL-1RI(-/-) animals exhibited enhanced glucose homeostasis by glucose tolerance test and insulin tolerance test. M1/M2 macrophage number in adipose tissue was comparable between genotypes; however, TNF-α and IL-6 secretion was lower from IL-1RI(-/-) adipose tissue macrophages. IL-1RI(-/-) adipose exhibited enhanced insulin sensitivity, elevated pAKT, lower cytokine secretion, and attenuated induction of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling molecule 3 after HFD. Coculture of WT, but not IL-1RI(-/-) macrophages, with 3T3L1 adipocytes enhanced IL-6 and TNF-α secretion, reduced adiponectin secretion, and impaired adipocyte insulin sensitivity. TNF-α and IL-1β potently synergized to enhance inflammation in WT macrophages and adipose, an effect lost in the absence of IL-1RI.Conclusions: Lack of IL-1RI protects against HFD-induced IR coincident with reduced local adipose tissue inflammation, despite equivalent immune cell recruitment. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: LDL phenotype B is associated with obesity, insulin resistance, hypertriglyceridemia and oxidative stress. The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated. METHODS: Patients with metabolic syndrome (n=99) received one of four isocaloric diets: (A) High-fat (38% energy) SFA-rich diet (HSFA); (B) High-fat (38% energy), MUFA-rich diet (HMUFA); (C), low-fat (LF) (28% energy), high-complex carbohydrate diet with 1.24g/d oleic sunflower oil (LFHCC) and (D): low-fat (28% energy), high-complex carbohydrate diet, with 1.24g/d LC n-3 PUFA (LFHCC n-3) for 12 weeks. Analysis of plasma lipid profile and LDL phenotype was done pre- and post-interventions. RESULTS: Post-dietary change of LDL density was a main effect observed in all groups. LFHCC n-3 and HFMUFA diets resulted in favorable alteration of LDL phenotype from B to A and decreased LDL density. In contrast, increased LDL density was observed in HSFA and LFHCC groups. The plasma pre-n3/n6 PUFA, Apo E change and pre-Apo CIII/CII ratios explained in 65% the post-dietary change of LDL density in diet LFHCC n-3 consumers. CONCLUSIONS: Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome. Study identifier at ClinicalTrials.gov was NCT00429195. [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW: Much attention has focused on the therapeutic potential of conjugated linoleic acid with the most abundant isomers being cis-9,trans-11 conjugated linoleic acid and trans-10,cis-12 conjugated linoleic acid. Initial animal studies associated conjugated linoleic acid with beneficial health properties, such as reducing the risk of cancer, diabetes, atherosclerosis, inflammation and obesity. This review has appraised the evidence in relation to the effect of conjugated linoleic acid on components of the metabolic syndrome (clinically or experimentally), in particular, obesity, insulin resistance, atherosclerosis and inflammation. RECENT FINDINGS: More recent human conjugated linoleic acid supplementation studies have often shown conflicting and less convincing health benefits. The marked variation between studies may reflect the isomer-specific effect of the individual conjugated linoleic acid isomers, which can often have opposing effects. Detrimental effects have been observed in some studies, in particular after supplementation with the trans-10,cis-12 conjugated linoleic acid isomer. SUMMARY: Further studies and long-term clinical trials will be required to determine the efficacy and safety of conjugated linoleic acid isomers before conjugated linoleic acid could be considered as a functional nutrient in humans. [ABSTRACT FROM AUTHOR]

Metabolomics has been widely adopted in pharmacology and toxicology but is relatively new in human nutrition. The ultimate goal, to understand the effects of exogenous compounds on human metabolic regulation, is similar in all 3 fields. However, the application of metabolomics to nutritional research will be met with unique challenges. Little is known of the extent to which changes in the nutrient content of the human diet elicit changes in metabolic profiles. Moreover, the metabolomic signal from nutrients absorbed from the diet must compete with the myriad of nonnutrient signals that are absorbed, metabolized, and secreted in both urine and saliva. The large-bowel microflora also produces significant metabolic signals that can contribute to and alter the metabolome of biofluids in human nutrition. Notwithstanding these possible confounding effects, every reason exists to be optimistic about the potential of metabolomics for the assessment of various biofluids in nutrition research. This potential lies both in metabolic profiling through the use of pattern-recognition statistics on assigned and unassigned metabolite signals and in the collection of comprehensive data sets of identified metabolites; both objectives have the potential to distinguish between different dietary treatments, which would not have been targeted with conventional techniques. The latter objective sets out a well-recognized challenge to modern biology: the development of libraries of small molecules to aid in metabolite identification. The purpose of the present review was to highlight some early challenges that need to be addressed if metabolomics is to realize its great potential in human nutrition. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

The metabolic syndrome is a very common disease associated with an increased risk of type 2 diabetes mellitus (T2DM) and CVD. The clinical characteristics of the metabolic syndrome include insulin resistance, dyslipidaemia, abdominal obesity and hypertension. The diverse clinical characteristics illustrate the complexity of the disease process, which involves several dysregulated metabolic pathways. Thus, multiple genetic targets must be involved in the pathogenesis and progression of the metabolic syndrome. Nevertheless, the human genome has not changed markedly in the last decade but the prevalence of the metabolic syndrome has increased exponentially, which illustrates the importance of gene-environmental interactions. There is good evidence that nutrition plays an important role in the development and progression of the metabolic syndrome. Indeed, obesity is a key aetiological factor in the development of the metabolic syndrome. Understanding the biological impact of gene-nutrient interactions will provide a key insight into the pathogenesis and progression of diet-related polygenic disorders, including the metabolic syndrome. The present paper will explore the interactions between genetic background and dietary exposure or nutritional therapy, focusing on the role of dietary fatty acids within the context of nutrient regulation of gene expression and individual responsiveness to dietary therapy. Only with a full understanding of gene-gene, gene-nutrient and gene-nutrient-environment interactions can the molecular basis of the metabolic syndrome be solved to minimise the adverse health effects of obesity and reduce the risk of the metabolic syndrome, and subsequent T2DM and CVD. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is a very common condition, characterised by insulin resistance, dyslipidaemia, abdominal obesity and hypertension, that is associated with a high risk of type 2 diabetes mellitus (T2DM) and CVD. Obesity is a key aetiological factor in the development of the metabolic syndrome. In light of the increasing prevalence of obesity, there is a high requirement to reduce the impact of the adverse health effects associated with the metabolic syndrome. The aetiological role of nutrient-derived metabolic stressors, in particular fatty acids, in the development of obesity and the metabolic syndrome is explored. Also, the evidence that pro-inflammatory stressors may predispose to obesity-induced insulin resistance is reviewed. The present paper explores the concept that reducing the impact of metabolic and inflammatory stressors may reduce the adverse health effects of obesity and slow the progression towards the metabolic syndrome and T2DM. Evidence from human dietary intervention studies that have investigated the potential therapeutic effects of dietary fatty acid modification is explored. The present review highlights the requirement to take account of genetic background, within the context of nutrient regulation of gene expression and individual responsiveness to dietary therapy. This approach will further the understanding of the interaction between fatty acids in the pathogenesis and progression of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND: Regular intake of plant sterol (phytosterol)-enriched foods enhances the cholesterol lowering effect of diets. One side effect associated with plant sterol consumption is a modest reduction in plasma carotenoid concentrations. This study investigated the effect of consuming a low-fat National Cholesterol Education Programme (NCEP) Step 1 diet, including a low-fat plant sterol ester (PSE)-enriched spread on cholesterol metabolism to determine if specific dietary advice to increase daily fruit and vegetable intake could prevent reduced plasma carotenoid concentrations. MATERIALS AND METHODS: In this randomised, crossover double-blind trial, 48 hypercholesterolaemic men received 21 g day(-1) of a low-fat PSE-enriched spread or placebo for 3 weeks, interrupted by 3 weeks washout. Individuals also adhered to a NCEP Step 1 diet and repeated 3-day food diaries monitored adherence. Specific advice was provided to increase dietary fruit and vegetable intakes. Fasting blood samples were collected at pre- and post-intervention for lipoprotein and carotenoid analysis. RESULTS: Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly (P <0.05) reduced, by 4.6 and 7.1%, respectively, after the PSE-enriched low-fat spread. Plasma apo B concentrations were significantly (P <0.0005) lower after the PSE spread. PSE consumption was also associated with significantly (P <0.05) lower total plasma beta-carotene concentrations, but this change was not significant after lipid standardisation. PSE consumption had no effect on retinol, alpha-carotene, gamma-tocopherol, alpha-tocopherol, lutein, zeaxanthin, beta-crypyoxanthin or lycopene concentrations. CONCLUSION: Dietary advice to increase daily fruit and vegetable consumption may be effective in preventing a reduction in plasma carotenoid concentrations previously associated with PSE consumption. Further, PSE incorporated in a low-fat spread and consumed as part of a NCEP Step 1 diet are effective in reducing total and LDL cholesterol. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study was an extension of a previous study that showed different lipemic responses to standard test meals in subjects from southern and northern Europe. OBJECTIVE: The aim was to determine in 32 healthy young men from northern and southern Europe whether differences in the secretion of insulin and glucose-dependent insulinotrophic polypeptide (GIP) might explain these findings through the actions of these hormones on lipoprotein lipase. DESIGN: We investigated in a randomized, single-blind, crossover study the effects of 2 test meals of identical macronutrient composition but different saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) contents on postprandial GIP, insulin, the ratio of incremental triacylglycerol to apolipoprotein B-48 (a marker of chylomicron size), and the activity of postheparin lipases. RESULTS: Fasting and postprandial GIP concentrations and postheparin hepatic lipase activities were significantly higher in the southern Europeans (P < 0.001 and P < 0.02, respectively). Lipoprotein lipase activity after the SFA-rich meal was significantly higher in the northern Europeans (P < 0.01). HL activity 9 h after the SFA-rich meal and the area under the curve (AUC) for the postprandial insulin response correlated with the AUC for the postprandial GIP response [r = 0.44 (P < 0.04) and r = 0.46 (P < 0.05), respectively]. There were no significant differences in chylomicron size between the 2 groups for either meal, but when the groups were combined there was a significant difference in chylomicron size between the SFA- and MUFA-rich meals (P < 0.05), which could be due to the formation of larger chylomicrons after the MUFA-rich meal. CONCLUSION: The significantly higher GIP and insulin responses and HL activities in southern Europeans may provide an explanation for our previous report of attenuated postprandial triacylglycerol and apolipoprotein B-48 responses in them. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Although the beneficial effects of Mediterranean-type diets, which are rich in olive oil, a good source of monounsaturated fatty acids (MUFAs), are generally accepted, little is known about the effects of long-term dietary MUFA intake on postprandial lipoprotein metabolism and hemostasis. This study used a single-blind, randomized, crossover design to investigate the relative effects of a long-term dietary olive oil intervention and a control [saturated fatty acid (SFA)-enriched] diet on postprandial triacylglycerol metabolism and factor VII activity. The postprandial response to a standard test meal was investigated in 23 healthy men who adhered to both diets for 8 wk. cis-MUFAs were successfully substituted for SFAs in the MUFA diet without affecting total dietary fat or energy intakes. The long-term dietary MUFA intervention significantly reduced plasma and LDL-cholesterol concentrations (P = 0.01). Postprandial triacylglycerol concentrations were significantly greater in the early postprandial period after the MUFA diet (P = 0.003). Postprandial factor VII activation and the concentration of the factor VII antigen were significantly lower after the MUFA diet (P = 0.04 and P = 0.006, respectively). This study showed that isoenergetic substitution of MUFAs for SFAs reduces plasma cholesterol and reduces the degree of postprandial factor VII activation. The alterations in the postprandial triacylglycerol response suggest a greater rate of dietary fat absorption and postprandial triacylglycerol metabolism after a diet rich in MUFAs. This study presents new insights into the biochemical basis of the beneficial effects associated with long-term dietary MUFA consumption, which may explain the lower rates of coronary mortality in Mediterranean regions. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Fibroblasts acquire a proinflammatory phenotype in inflammatory bowel disease, but the factors driving this process and how fibroblasts contribute to mucosal immune responses are incompletely understood. TNF superfamily member 12 (TNFSF12, or TNF-like weak inducer of apoptosis [TWEAK]) has gained interest as a mediator of chronic inflammation. In this study, we explore its role as a driver of inflammatory responses in fibroblasts and its contribution to fibroblast-monocyte interaction using human primary colonic fibroblasts, THP-1 and primary monocytes. Recombinant human TWEAK induced the expression of cytokines, chemokines, and immune receptors in primary colonic fibroblasts. The TWEAK upregulated transcriptome shared 29% homology with a previously published transcriptional profile of inflammatory fibroblasts from ulcerative colitis. TWEAK elevated surface expression of activated fibroblast markers and adhesion molecules (podoplanin [PDPN], ICAM-1, and VCAM-1) and secretion of IL-6, CCL2, and CXCL10. In coculture, fibroblasts induced monocyte adhesion and secretion of CXCL1 and IL-8, and they promoted a CD14high/ICAM-1high phenotype in THP-1 cells, which was enhanced when fibroblasts were prestimulated with TWEAK. Primary monocytes in coculture with TWEAK-treated fibroblasts had altered surface expression of CD16 and triggering receptor expressed on myeloid cells-1 (TREM-1) as well as increased CXCL1 and CXCL10 secretion. Conversely, inhibition of the noncanonical NF-κB pathway on colonic fibroblasts with a NF-κB-inducing kinase small molecule inhibitor impaired their ability to induce a CD14high phenotype on monocytes. Our results indicate that TWEAK promotes an inflammatory fibroblast-monocyte crosstalk that may be amenable for therapeutic intervention., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Obesity is a major driving factor in the incidence, progression, and poor treatment response in gastrointestinal cancers. Herein, we conducted a comprehensive analysis of the impact of obesity and its resulting metabolic perturbations across four gastrointestinal cancer types, namely, oesophageal, gastric, liver, and colorectal cancer. Importantly, not all obese phenotypes are equal. Obese adipose tissue heterogeneity depends on the location, structure, cellular profile (including resident immune cell populations), and dietary fatty acid intake. We discuss whether adipose heterogeneity impacts the tumorigenic environment. Dietary fat quality, in particular saturated fatty acids, promotes a hypertrophic, pro-inflammatory adipose profile, in contrast to monounsaturated fatty acids, resulting in a hyperplastic, less inflammatory adipose phenotype. The purpose of this review is to examine the impact of obesity, including dietary fat quality, on adipose tissue biology and oncogenesis, specifically focusing on lipid metabolism and inflammatory mechanisms. This is achieved with a particular focus on gastrointestinal cancers as exemplar models of obesity-associated cancers.

Creating effective dietary guidance requires a rigorous evidence base that is predominantly developed from robust clinical trials or large-scale cohort studies, with the quality of the data available depending on the completeness and accuracy of their reporting. An international group of academics from 14 institutions in 12 different countries and on 5 continents, working on behalf of the Federation of European Nutrition Societies within its "Improving Standards in the Science of Nutrition" initiative, reviewed the Consolidated Standards of Reporting Trials (CONSORT) statement checklist as it pertains to nutrition trials. This perspective piece documents the procedure followed to gain input and consensus on the checklist previously published by this group, including its presentation and interrogation at the International Union of Nutritional Sciences International Congress of Nutrition 2022 (IUNS-ICN 22), inputs from a survey of journal editors, and its piloting on 8 nutrition trials of diverse designs. Overall, the initiative has been met with considerable enthusiasm. At IUNS-ICN 22, refinements to our proposal were elicited through a World Café method discussion with participating nutrition scientists. The contributing journal editors provided valuable insights, and the discussion led to the development of a potential tool specific to assess adherence to the proposed nutrition extension checklist. The piloting of the proposed checklist provided evidence from real-life studies that reporting of nutrition trials can be improved. This initiative aims to stimulate further discussion and development of a CONSORT-nutrition-specific extension., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Milk-derived peptides are known to confer anti-inflammatory effects. We hypothesised that milk-derived cell-penetrating peptides might modulate inflammation in useful ways. Using computational techniques, we identified and synthesised peptides from the milk protein Alpha-S1-casein that were predicted to be cell-penetrating using a machine learning predictor. We modified the interpretation of the prediction results to consider the effects of histidine. Peptides were then selected for testing to determine their cell penetrability and anti-inflammatory effects using HeLa cells and J774.2 mouse macrophage cell lines. The selected peptides all showed cell penetrating behaviour, as judged using confocal microscopy of fluorescently labelled peptides. None of the peptides had an effect on either the NF-κB transcription factor or TNFα and IL-1β secretion. Thus, the identified milk-derived sequences have the ability to be internalised into the cell without affecting cell homeostatic mechanisms such as NF-κB activation. These peptides are worthy of further investigation for other potential bioactivities or as a naturally derived carrier to promote the cellular internalisation of other active peptides.

Obesity is a heterogenous disease accompanied by a broad spectrum of cardiometabolic risk profiles. Traditional paradigms for dietary weight management do not address biological heterogeneity between individuals and have catastrophically failed to combat the global pandemic of obesity-related diseases. Nutritional strategies that extend beyond basic weight management to instead target patient-specific pathophysiology are warranted. In this narrative review, we provide an overview of the tissue-level pathophysiological processes that drive patient heterogeneity to shape distinct cardiometabolic phenotypes in obesity. Specifically, we discuss how divergent physiology and postprandial phenotypes can reveal key metabolic defects within adipose, liver, or skeletal muscle, as well as the integrative involvement of the gut microbiome and the innate immune system. Finally, we highlight potential precision nutritional approaches to target these pathways and discuss recent translational evidence concerning the efficacy of such tailored dietary interventions for different obesity phenotypes, to optimise cardiometabolic benefits., (© 2023. The Author(s).)

Diminished skeletal muscle strength and size, termed sarcopenia, contributes substantially to physical disability, falls, dependence and reduced quality of life among older people. Physical activity and nutrition are the cornerstones of sarcopenia prevention and treatment. The optimal daily protein intake required to preserve muscle mass and function among older adults is a topic of intense scientific debate. Older adults require protein intakes about 67 % higher than their younger counterparts to maximally stimulate postprandial muscle protein synthesis rates. In addition, evidence suggests a possible benefit of increasing protein intake above the population reference intake (0⋅83 g/kg/d) on lean mass and, when combined with exercise training, muscle strength. In addition to protein quantity, protein quality, the pattern of protein intake over the day and specific amino acids (i.e. leucine) represent key considerations. Long-chain n -3 PUFA (LC n- 3 PUFA) supplementation has been shown to enhance muscle protein synthesis rates, increase muscle mass and function and augment adaptations to resistance training in older adults. Yet, these effects are not consistent across all studies. Emerging evidence indicates that an older person's dietary, phenotypic and behavioural characteristics may modulate the efficacy of protein and LC n -3 PUFA interventions for promoting improvements in muscle mass and function, highlighting the potential inadequacy of a 'one-size-fits-all' approach. The application of personalised or precision nutrition to sarcopenia represents an exciting and highly novel field of research with the potential to help resolve inconsistencies in the literature and improve the efficacy of dietary interventions for sarcopenia.

Background: Data on the prevalence of sarcopenia among older adults in Ireland are lacking., Aims: To assess the prevalence and determinants of sarcopenia among community-dwelling older adults in Ireland., Methods: This cross-sectional analysis involved n = 308 community-dwelling adults aged ≥ 65 y living in Ireland. Participants were recruited via recreational clubs and primary healthcare services. Sarcopenia was defined according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Skeletal muscle mass was estimated using bioelectrical impedance analysis, strength was measured via handgrip dynamometry, and physical performance was assessed using the Short Physical Performance Battery. Detailed information was collected on demographics, health, and lifestyle. Dietary macronutrient intake was measured via a single 24 h recall. Binary logistic regression was used to examine potential demographic, health, lifestyle, and dietary determinants of sarcopenia (where both probable and confirmed sarcopenia were combined)., Results: The prevalence of EWGSOP2-defined probable sarcopenia was 20.8% and confirmed sarcopenia was 8.1% (5.8% had severe sarcopenia). Polypharmacy (OR 2.60, 95% confidence interval [CI] 1.3, 5.23), height (OR 0.95, 95% CI 0.91, 0.98), and Instrumental Activities Of Daily Living (IADL) score (OR 0.71, 95% CI 0.59, 0.86) were independently associated with sarcopenia (probable and confirmed combined). There were no independent associations between energy-adjusted macronutrient intakes, as determined by 24 h recall, and sarcopenia., Conclusion: Sarcopenia prevalence within this sample of community-dwelling older adults in Ireland is broadly similar to other European cohorts. Polypharmacy, lower height, and lower IADL score were independently associated with EWGSOP2-defined sarcopenia., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The precision nutrition paradigm is based on the premise that substantial variation exists between human subjects in terms of diet-related disease risk and response to dietary interventions. In terms of better defining, 'the right diet for the right person at the right time' may be more appropriate than 'one-diet-fits-all'. This review will explore how systems biology and nutrigenomics approaches have advanced the precision nutrition paradigm. We will draw upon a number of elegant mechanistic studies that have enhanced our understanding with respect to the complex biology and inter-organ crosstalk, relating to inflammation and metabolism, that underpin cardio-metabolic health. Also, this review will explore the extent to which more targeted, precision nutrition approaches may attenuate adverse risk factors associated with cardio-metabolic disease. We will focus on the key characteristics or 'metabotypes' of high- v. low-risk individuals and response v. non-response to interventions, to generate greater insights with respect to risk stratification and therapeutic interventions to enhance disease prevention. The goal is to utilise systems biology to enhance understanding by underpinning more targeted nutritional approaches, which may improve efficacy of personalised nutrition interventions.

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients ( n = 32). Compared to visceral fat from non-obese patients ( n = 16), visceral fat explants from obese OAC patients ( n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy ( n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-β and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes.

Introduction: Oxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC n-3 PUFA supplementation., Materials and Methods: This exploratory study investigated the baseline correlations between LC n-3, n-6 and n-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (n = 49). After examining the baseline relationship, the potential effect of supplementation (LC n-3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined., Results: At baseline, the hydroxy product of mead acid (n-9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (p = 0.003, r=-0.41), skeletal muscle mass index (SMMI) (p = 0.001, r=-0.46), handgrip strength (HGS) (p<0.001, r = 0.48) and isometric knee extension (p<0.001, r=-0.48). Likewise, LC n-6 PUFA hydroxy‑PUFA were negatively correlated to HGS (i.e., 12-HETrE, p = 0.002, r=-0.42, and 5- and 11-HETE, p = 0.006, r=-0.47 and p<0.001, r=-0.50 respectively), single leg stand time (i.e., 12-HETrE, p = 0.006, r=-0.39 and 16-HETE, p = 0.002, r=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, p = 0.006, r = 0.39), and positively correlated to gait speed (i.e., 12-HETrE, p = 0.007, r = 0.38 and 16-HETE, p = 0.006, r = 0.39). LC n-3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced n-6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC n-3 PUFA or placebo groups. Changes in plasma oxylipins concentrations were closely related to changes in their parent PUFA, assessed in the erythrocyte membrane, but were not associated with any changes in skeletal muscle parameters., Discussion and Conclusion: At baseline, the status n-9 (5-HETrE) and n-6 PUFA derivates [12-HETrE, and 5-, 11- and 16-HETE], but not n-3 PUFA derived oxylipins, were associated with poor skeletal muscle health parameters (i.e., mass and strength). However, these correlations were no longer present when correlating relative changes from pre to post timepoints. An independent cohort validation is needed to explore baseline correlations further. Further research is warranted to assess other biological mechanisms by which LC n-3 PUFA might affect muscle biology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1-3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.