Background Leucine-enriched protein (LEU-PRO) and long-chain (LC) n–3 (ω–3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. Objective The impact of LEU-PRO supplementation alone and combined with LC n–3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. Methods This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n–3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n–3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). Results Neither LEU-PRO nor LEU-PRO+n–3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: −7.1 Nm; 95% CI: −12.5, −1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n–3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n–3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n–3 postsupplementation compared with CON (all P < 0.05). Conclusions Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n–3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.
Metabolic inflammation (metaflammation) is characteristic of obesity-related metabolic disorders, associated with increased risk of development of type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), or cardiovascular disease. Metaflammation refers to a chronic, low-grade systemic inflammation as opposed to the classical transient and acute inflammatory responses of the innate immune system. Metaflammation is driven by a range of adverse dietary factors, including saturated fatty acids and some sugars, suggesting that certain dietary triggers may be particularly relevant beyond simple excessive dietary intake presenting as obesity. Importantly, obese patients with diabetes have a higher risk of infection and display gut microbiota profiles characteristic of dysfunctional immunity. Targeting metaflammation has also emerged as a strategy to attenuate metabolic disease. In this review we explore how different nutrition interventions may reconfigure disrupted metabolic inflammation in type 2 diabetes and nonalcoholic fatty liver disease by reestablishing a conventional proinflammatory program in innate immune cells and/or correcting dysbiosis to dampen systemic inflammation. We begin by reviewing concepts of metabolic inflammation relating to IL-1b inflammation and how it is induced by dietary and/or metabolic stressors. We then explore whether and how dietary interventions may attenuate processes pertaining to metaflammation, either directly or indirectly via the microbiome. Hence, we hope to bring new perspectives to alleviate the metaflammation typifying metabolic disease.
Background Precision nutrition is highly topical. However, no studies have explored the interindividual variability in response to nutrition interventions for sarcopenia. The purpose of this study was to determine the magnitude of interindividual variability in response to two nutrition supplementation interventions for sarcopenia and metabolic health, after accounting for sources of variability not attributable to supplementation. Methods A 24 week, randomized, double‐blind, placebo‐controlled trial tested the impact of leucine‐enriched protein (LEU‐PRO), LEU‐PRO plus long‐chain n‐3 PUFA (LEU‐PRO+n‐3) or control (CON) supplementation in older adults (n = 83, 71 ± 6 years) at risk of sarcopenia. To estimate the true interindividual variability in response to supplementation (free of the variability due to measurement error and within‐subject variation), the standard deviation of individual responses (SDR) was computed and compared with the minimally clinically important difference (MCID) for appendicular lean mass (ALM), leg strength, timed up‐and‐go (TUG), and serum triacylglycerol (TG) concentration. Clinically meaningful interindividual variability in response to supplementation was deemed to be present when the SDR positively exceeded the MCID. The probability that individual responses were clinically meaningful, and the phenotypic, dietary, and behavioural determinants of response to supplementation were examined. Results The SDR was below the MCID for ALM (LEU‐PRO: −0.12 kg [90% CI: −0.38, 0.35], LEU‐PRO+n‐3: −0.32 kg [−0.45, 0.03], MCID: 0.21 kg), TUG (LEU‐PRO: 0.58 s [0.18, 0.80], LEU‐PRO+n‐3: 0.73 s [0.41, 0.95], MCID: 0.9 s) and TG (LEU‐PRO: −0.38 mmol/L [−0.80, 0.25], LEU‐PRO+n‐3: −0.44 mmol/L [−0.63, 0.06], MCID: 0.1 mmol/L), indicating no meaningful interindividual variability in response to either supplement. The SDR exceeded the MCID (19 Nm) for strength in response to LEU‐PRO (25 Nm [−29, 45]) and LEU‐PRO+n‐3 (23 Nm [−29, 43]) supplementation but the effect was uncertain, evidenced by wide confidence intervals. In the next stage of analysis, similar proportions of participant responses were identified as very likely, likely, possibly, unlikely, and very unlikely to represent clinically meaningful improvements across the LEU‐PRO, LEU‐PRO+n‐3, and CON groups (P > 0.05). Baseline LC n‐3 PUFA status, habitual protein intake, and numerous other phenotypic and behavioural factors were not determinants of response to LEU‐PRO or LEU‐PRO+n‐3 supplementation. Conclusions Applying a novel, robust methodological approach to precision nutrition, we show that there was minimal interindividual variability in changes in ALM, muscle function, and TG in response to LEU‐PRO and LEU‐PRO+n‐3 supplementation in older adults at risk of sarcopenia.
Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of adipose tissue may provide insight for this observation. We hypothesised that different metabolic pathways predominate in visceral (VAT) and subcutaneous adipose tissue (SAT) and inflammatory secretions will differ between the fat depots. Real-time ex vivo metabolic profiles of VAT and SAT from 12 OAC patients were analysed. These samples were screened for the secretion of 54 inflammatory mediators, and data were correlated with patient body composition. Oxidative phosphorylation (OXPHOS) was significantly higher in VAT when compared to SAT. OXPHOS was significantly higher in the SAT of patients receiving neoadjuvant treatment. VEGF-A, VEGF-C, P1GF, Flt-1, bFGF, IL-15, IL-16, IL-17A, CRP, SAA, ICAM-1, VCAM-1, IL-2, IL-13, IFN-γ, and MIP-1β secretions were significantly higher from VAT than SAT. Higher levels of bFGF, Eotaxin-3, and TNF-α were secreted from the VAT of obese patients, while higher levels of IL-23 and TARC were secreted from the SAT of obese patients. The angiogenic factors, bFGF and VEGF-C, correlated with visceral fat area. Levels of OXPHOS are higher in VAT than SAT. Angiogenic, vascular injury and inflammatory cytokines are elevated in VAT versus SAT, indicating that VAT may promote inflammation, linked to regulating treatment response.
ScopeIL‐1RI‐mediated inflammatory signaling alters metabolic tissue responses to dietary challenges (e.g., high‐fat diet [HFD]). Recent work suggests that metabolic phenotype is transferrable between mice in a shared living environment (i.e., co‐housing) due to gut microbiome exchange. The authors examine whether the metabolic phenotype of IL‐1RI−/− mice fed HFD or low‐fat diet (LFD) could be transferred to wild‐type (WT) mice through gut microbiome exchange facilitated by co‐housing.Methods and resultsMale WT (C57BL/J6) and IL‐1RI−/− mice are fed HFD (45% kcal) or LFD (10% kcal) for 24 weeks and housed i) by genotype (single‐housed) or ii) with members of the other genotype in a shared microbial environment (co‐housed). The IL‐1RI−/− gut microbiome is dominant to WT, meaning that co‐housed WT mice adopted the IL‐1RI−/− microbiota profile. This is concomitant with greater body weight, hepatic lipid accumulation, adipocyte hypertrophy, and hyperinsulinemia in co‐housed WT mice, compared to single‐housed counterparts. These effects are most evident following HFD. Primary features of microbiome differences are Lachnospiraceae and Ruminococcaceae (known producers of SCFA).ConclusionTransfer of SCFA‐producing microbiota from IL‐1RI−/− mice highlights a new connection between diet, inflammatory signaling, and the gut microbiome, an association that is dependent on the nature of the dietary fat challenge.
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