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.

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.

As COVID-19 continues to spread worldwide, severe disease and mortality have been observed in obese patients. We discuss how obesity and obesity-associated factors such as ‘meta-flammation’, dietary fat intake and paradoxical suppression of the innate immune response within the pulmonary compartment may be crucial determinants in the host response to a novel viral pathogen. Modulation of immune cell bioenergetics and metabolic potential plays a central role in the innate immune response to infection, and as we strive to combat this new global health threat, immunometabolism of the innate immune system warrants attention.

Reduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.

Preliminary evidence has suggested that high-fat diets (HFD) enriched with SFA, but not MUFA, promote hyperinsulinaemia and pancreatic hypertrophy with insulin resistance. The objective of this study was to determine whether the substitution of dietary MUFA within a HFD could attenuate the progression of pancreatic islet dysfunction seen with prolonged SFA-HFD. For 32 weeks, C57BL/6J mice were fed either: (1) low-fat diet, (2) SFA-HFD or (3) SFA-HFD for 16 weeks, then switched to MUFA-HFD for 16 weeks (SFA-to-MUFA-HFD). Fasting insulin was assessed throughout the study; islets were isolated following the intervention. Substituting SFA with MUFA-HFD prevented the progression of hyperinsulinaemia observed in SFA-HFD mice (P < 0·001). Glucose-stimulated insulin secretion from isolated islets was reduced by SFA-HFD, yet not fully affected by SFA-to-MUFA-HFD. Markers of β-cell identity (Ins2, Nkx6.1, Ngn3, Rfx6, Pdx1 and Pax6) were reduced, and islet inflammation was increased (IL-1β, 3·0-fold, P = 0·007; CD68, 2·9-fold, P = 0·001; Il-6, 1·1-fold, P = 0·437) in SFA-HFD – effects not seen with SFA-to-MUFA-HFD. Switching to MUFA-HFD can partly attenuate the progression of SFA-HFD-induced hyperinsulinaemia, pancreatic inflammation and impairments in β-cell function. While further work is required from a mechanistic perspective, dietary fat may mediate its effect in an IL-1β–AMP-activated protein kinase α1-dependent fashion. Future work should assess the potential translation of the modulation of metabolic inflammation in man.

Dietary intake and nutritional status is an important environmental factor which can modulate metabolic-inflammation. In recent years, research has made significant advances in terms of understanding the impact of dietary components on metabolic-inflammation, within the context of obesity, type-2 diabetes (T2D) and CVD risk. Our work demonstrated that different fatty acids differentially modulate metabolic-inflammation, initially focusing on Nod-like receptor family, pyrin domain-containing three protein (NLRP3) inflammasome mediated IL-1β biology and insulin signalling. However, the paradigm is more complex, wherein data from the immunology field clearly show that nature of cellular energy metabolism is a key determinant of inflammation. Whilst metabolic-inflammation is a critical biological interaction, there is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation. The complex paradigm will be discussed within the context of if/how dietary components, in particular fatty acids, may modulate obesity, T2D and CVD risk, via inflammatory and metabolic processes.

SFA intakes have decreased in recent years, both in Ireland and across other European countries; however a large proportion of the population are still not meeting the SFA recommendation of <10% of total energy (TE). High SFA intakes have been associated with increased CVD and type-2 diabetes (T2D) risk, due to alterations in cholesterol homoeostasis and adipose tissue inflammation. PUFA, in particular EPA and DHA, have been associated with health benefits, including anti-inflammatory effects. It is well established that dietary fat composition plays an important role in biological processes. A recent review of evidence suggests that replacement of SFA with PUFA has potential to reduce risk of CVD and T2D. The public health and molecular impact of EPA and DHA have been well-characterised, while less is known of effects of α-linolenic acid (ALA). The current dietary guideline for ALA is 0·5% TE; however evidence from supplementation trials suggests that benefit is observed at levels greater than 2 g/d (0·6–1% TE). This review highlights the gap in the evidence base relating to effects of the replacement of SFA with ALA, identifying the need for randomised controlled trials to determine the optimal dose of ALA substitution to define the efficacy of dietary fat modification with ALA.

FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health.

Evidence suggests that processed red meat consumption is a risk factor for CVD and type 2 diabetes (T2D). This analysis investigates the association between dietary patterns, their processed red meat contributions, and association with blood biomarkers of CVD and T2D, in 786 Irish adults (18–90 years) using cross-sectional data from a 2011 national food consumption survey. All meat-containing foods consumed were assigned to four food groups (n 502) on the basis of whether they contained red or white meat and whether they were processed or unprocessed. The remaining foods (n 2050) were assigned to twenty-nine food groups. Two-step and k-means cluster analyses were applied to derive dietary patterns. Nutrient intakes, plasma fatty acids and biomarkers of CVD and T2D were assessed. A total of four dietary patterns were derived. In comparison with the pattern with lower contributions from processed red meat, the dietary pattern with greater processed red meat intakes presented a poorer Alternate Healthy Eating Index (21·2 (sd 7·7)), a greater proportion of smokers (29 %) and lower plasma EPA (1·34 (sd 0·72) %) and DHA (2·21 (sd 0·84) %) levels (P<0·001). There were no differences in classical biomarkers of CVD and T2D, including serum cholesterol and insulin, across dietary patterns. This suggests that the consideration of processed red meat consumption as a risk factor for CVD and T2D may need to be re-assessed.

Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Evidence suggests that at a population level, childhood and adolescent obesity increase the long-term risk of chronic diseases such as type 2 diabetes and CVD. At an individual level, however, the metabolic consequences of obesity in youth vary immensely. Despite comparable BMI, some adolescents develop impaired glucose tolerance while others maintain normal glucose homeostasis. It has been proposed that the variation in the capacity to store lipid in the subcutaneous adipose tissue (SAT) may partially discriminate metabolically healthy from unhealthy obesity. In positive energy balance, a decreased capacity to expand SAT may drive lipid accumulation to visceral adipose tissue, liver and skeletal muscle. This state of lipotoxicity is associated with chronic low-grade inflammation, insulin resistance and dyslipidaemia. The present review examines the differential adipose tissue development and function in children and adolescents who exhibit metabolic dysregulation compared with those who are protected. Additionally, the role of manipulating dietary fat quality to potentially prevent and treat metabolic dysfunction in obesity will be discussed. The findings of the present review highlight the need for further randomised controlled trials to establish the effect of dietary n-3 PUFA on the metabolic phenotype of obese children and adolescents. Furthermore, using a personalised nutrition approach to target interventions to those at risk of, or those with established metabolic dysregulation may optimise the efficacy of modifying dietary fat quality.

The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R2X: 0·33, Q2: 0·39) and plasma fatty acid (R2X: 0·32, Q2: 0·60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0·001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0·001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.

The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO2 and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD.

High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

The role of metabolomics in the field of nutrition is continuing to grow and it has the potential to assist in the understanding of metabolic regulation and explain how minor perturbations can have a multitude of biochemical endpoints. It is this development, which creates the potential to provide the knowledge necessary to facilitate a more targeted approach to nutrition. In recent years, there has been interest in applying metabolomics to examine alterations in the metabolic profile according to weight gain/obesity. Emerging from these studies is the strong evidence that alterations in the amino acid (AA) profiles are associated with obesity. Several other studies have also shown a relationship between branched-chain amino acids (BCAA), obesity and insulin resistance. The present review focuses on the proposed link between AA and in particular BCAA, obesity and insulin resistance. In conclusion, a wealth of information is accumulating to support the role of AA, and in particular of the BCAA, in obesity.

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.