Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n–3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial

peer-reviewedBackground 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.Horizon 2020 Framework ProgrammeThis work was supported by the Department of Agriculture, Food and the Marine Food Institutional Research Measure grant entitled NUTRIMAL “Novel Nutritional Solutions for the Prevention of Malnutrition” (grant 14F822), the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 666010, and a Research Fellowship awarded to CHM by the European Society of Clinical Nutrition and Metabolism (ESPEN). HMR was supported by funding from the Joint Programming Initiative Healthy Diet for a Healthy Life (JPI HDHL) EU Food Biomarkers Alliance “FOODBAll” with Science Foundation Ireland (14/JPHDHL/B3076)

Obesity, dietary fats, and gastrointestinal cancer risk-potential mechanisms relating to lipid metabolism and inflammation

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

Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction

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