Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.

Human milk fat is specially tailored to supply the developing infant with adequate and balanced nutrients. The present study aimed to quantify the composition of fatty acids, tocopherols and carotenoids in human milk, with special emphasis on the lactational changes. Colostrum, transitional and mature milk samples were collected longitudinally from the same forty-two healthy, well-nourished Chinese mothers. Fatty acids were quantified by GC with carotenoids (carotenes and xanthophylls) and tocopherols (α-, γ-tocopherol) determined by HPLC. Total fatty acid (TFA) content increased from 15·09 g/l in colostrum to 32·57 g/l in mature milk with the percentages of DHA and arachidonic acid (ARA) decreased. The ratio of n-6:n-3 PUFA and ARA:DHA remained constant during lactation at about 11:1 and 1·3:1, respectively. Both α-tocopherol and γ-tocopherol decreased over lactation with the ratio of α-:γ-tocopherol declined significantly from 7·21:1 to 4·21:1 (P < 0·001). Carotenoids all dropped from colostrum to mature milk as the less polar carotenes dropped by 88·67 %, while xanthophylls only dropped by 35·92 %. Lutein was predominated in both transitional and mature milk carotenoids (51·64–52·49 %), while colostrum carotenoids were mainly composed of lycopene (32·83 %) and β-carotene (30·78 %). The concentrations of tocopherols and xanthophylls but not carotenes were positively associated with TFA content in milk. These results suggested that colostrum and mature milk contained divergent lipid profiles and selective transfer mechanisms related to polarity might be involved. The present outcomes provide new insights for future breast-feeding studies, which also add in scientific evidences for the design of both initial and follow-on infant formulas.

Oxidative damage of cells and tissues is broadly implicated in human pathophysiology, including cardiometabolic diseases. Polyphenols, as important constituents of the human diet and potent in vitro free radical scavengers, have been extensively studied for their beneficial effects on cardiometabolic health. However, it has been demonstrated that the in vivo antioxidant activity of polyphenols is distinct from their in vitro free radical-scavenging capacity. Indeed, bioavailability of nutritional polyphenols is low and conditioned by complex mechanisms of absorption, distribution, metabolism and excretion. Nowadays, it is commonly accepted that the cellular antioxidant activity of polyphenols is mainly carried out via modification of transcription of genes involved in antioxidant defence. Importantly, polyphenols also contribute to cardiometabolic health by modulation of a plethora of cellular processes that are not directly associated with antioxidant enzymes, through nutri(epi)genomic mechanisms. Numerous human intervention studies have demonstrated beneficial effects of polyphenols on the key cardiometabolic risk factors. However, inconsistency of the results of some studies led to identification of the inter-individual variability in response to consumption of polyphenols. In perspective, a detailed investigation of the determinants of this inter-individual variability will potentially lead us towards personalised dietary recommendations. The phenomenon of inter-individual variability is also of relevance for supplementation with antioxidant (pro)vitamins.

The bioaccessibility of fat has implications for satiety and postprandial lipidaemia. The prevailing view holds that the integrity of plant cell wall structure is the primary determinant of energy and nutrient extraction from plant cells as they pass through the gastrointestinal (GI) tract. However, comparisons across nuts (walnuts, almonds and pistachios) with varying physical properties do not support this view. In the present study, masticated samples of three nuts from healthy adults were exposed to a static model of gastric digestion followed by simulated intestinal digestion. Primary outcomes were particle size and lipid release at each phase of digestion. Walnuts produced a significantly larger particle size post-mastication compared with almonds. Under gastric and intestinal conditions, the particle size was larger for walnuts compared with pistachios and almonds (P < 0·05). However, the masticated and digesta particle sizes were not related to the integrity of cell walls or lipid release. The total lipid release was comparable between nuts after the in vitro intestinal phase (P > 0·05). Microstructural examination showed ruptured and fissured cell walls that would allow digestion of cellular contents, and this may be governed by internal cellular properties such as oil body state. Furthermore, the cell walls of walnuts tend to rupture rather than separate and as walnut tissue passes through the GI tract, lipids tend to coalesce reducing digestion efficiency.

The nutritional intake of Tibetan sheep on the harsh Qinghai–Tibetan Plateau is often under maintenance requirements, especially during the long, cold winter. However, they have adapted well and even thrive under these conditions. The aim of the present study was to gain insight into how the rumen epithelium of Tibetan sheep has adapted to the consumption of low-energy-level diets. For this purpose, we compared Tibetan and small-tailed Han sheep (n 24 of each breed, all wethers and 1·5 years of age), which were divided randomly into one of four groups and offered ad libitum diets of different digestible energy (DE) densities: 8·21, 9·33, 10·45 and 11·57 MJ DE/kg DM. The Tibetan sheep had higher rumen concentrations of total SCFA, acetate, butyrate and iso-acids but lower concentrations of propionate than small-tailed Han sheep. The Tibetan sheep had higher absorption capability of SCFA due to the greater absorption surface area and higher mRNA expression of the SCFA absorption relative genes than small-tailed Han sheep. For the metabolism of SCFA in the rumen epithelium, the small-tailed Han sheep showed higher utilisation of the ketogenesis pathway than Tibetan sheep; however, Tibetan sheep had greater regulation capacity in SCFA metabolism pathways. These differences between breeds allowed the Tibetan sheep to have greater capability of absorbing SCFA and better capacity to regulate the metabolism of SCFA, which would allow them to cope with low energy intake better than small-tailed Han sheep.

Studies on the impact of Ramadan diurnal intermittent fasting (RDIF) on the metabolic syndrome (MetS) components among healthy Muslims observing Ramadan month have yielded contradictory results. This comprehensive meta-analysis aimed to obtain a more stable estimate of the effect size of fasting during Ramadan on the MetS components, examine variability among studies, assess the generalisability of reported results and perform subgroup analyses for associated factors. We searched the CINAHL, Cochrane, EBSCOhost, Google Scholar, ProQuest Medical, PubMed/MEDLINE, ScienceDirect, Scopus and Web of Science databases for relevant studies published from 1950 to March 2019. The MetS components analysed were: waist circumference (WC), systolic blood pressure (SBP), fasting plasma/serum glucose (FG), TAG, and HDL-cholesterol. We identified eighty-five studies (4326 participants in total) that were conducted in twenty-three countries between 1982 and 2019. RDIF-induced effect sizes for the MetS components were: small reductions in WC (no. of studies K = 24, N 1557, Hedges’ g = −0·312, 95 % CI −0·387, −0·236), SBP (K = 22, N 1172, Hedges’ g = −0·239, 95 % CI −0·372, −0·106), FG (K = 51, N 2318, Hedges’ g = −0·101, 95 % CI −0·260, 0·004) and TAG (K = 63, N 2862, Hedges’ g = −0·088, 95 % CI −0·171, −0·004) and a small increase in HDL-cholesterol (K = 57, N 2771, Hedges’ g = 0·150, 95 % CI 0·064, 0·236). We concluded that among healthy people, RDIF shows small improvement in the five MetS components: WC, SBP, TAG, FG and HDL.

The experiment was conducted to investigate the effects of dietary threonine (Thr) on growth performance and muscle growth, protein synthesis and antioxidant-related signalling pathways of hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. A total of 1200 fish (14·19 (se 0·13) g) were randomly distributed into six groups with four replicates each, fed six diets with graded level of Thr (9·5, 11·5, 13·5, 15·4, 17·4 and 19·3 g/kg diets) for 56 d. Results showed (P < 0·05) that dietary Thr (1) increased percentage weight gain, specific growth rate, feed efficiency and protein efficiency ratio; (2) up-regulated growth hormone (GH), insulin-like growth factor 1 (IGF-1), proliferating cell nuclear antigen, myogenic regulation factors (MyoD, Myf5, MyoG and Mrf4) and myosin heavy chain (MyHC) mRNA levels; (3) increased muscle protein content via regulating the protein kinase B/target of rapamycin signalling pathway and (4) decreased malondialdehyde and protein carbonyl contents, increased catalase, glutathione-S-transferase, glutathione reductase and GSH activities, up-regulated mRNA levels of antioxidant enzymes related to NFE2-related factor 2 and γ-glutamylcysteine ligase catalytic subunit. These results suggest that Thr has a potential role to improve muscle growth and protein synthesis, which might be due to the regulation of GH-IGF system, muscle growth-related gene, antioxidative capacity and protein synthesis-related signalling pathways. Based on the quadratic regression analysis of specific growth rate, the Thr requirement of hybrid catfish (14·19–25·77 g) was estimated to be 13·77 g/kg of the diet (33·40 g/kg of dietary protein).

Foamy, whitish appearance of the pyloric caeca, reflecting elevated lipid content, histologically visible as hypervacuolation, is frequently observed in Atlantic salmon fed high-plant diets. Lipid malabsorption syndrome (LMS) is suggested as term for the phenomenon. Earlier studies have shown that insufficient supply of phospholipids may cause similar symptoms. The objective of the present study was to strengthen knowledge on the role of choline, the key component of phosphatidylcholine, in development of LMS as well as finding the dietary required choline level in Atlantic salmon. A regression design was chosen to be able to estimate the dietary requirement level of choline, if found essential for the prevention of LMS. Atlantic salmon (456 g) were fed diets supplemented with 0, 392, 785, 1177, 1569, 1962, 2354, 2746 and 3139 mg/kg choline chloride. Fish fed the lowest-choline diet had pyloric caeca with whitish foamy surface, elevated relative weight, and the enterocytes were hypervacuolated. These characteristics diminished with increasing choline level and levelled off at levels of 2850, 3593 and 2310 mg/kg, respectively. The concomitant alterations in expression of genes related to phosphatidylcholine synthesis, cholesterol biosynthesis, lipid transport and storage confirmed the importance of choline in lipid turnover in the intestine and ability to prevent LMS. Based on the observations of the present study, the lowest level of choline which prevents LMS and intestinal lipid hypervacuolation in post-smolt Atlantic salmon is 3·4 g/kg. However, the optimal level most likely depends on the feed intake and dietary lipid level.

Time-restricted feeding (TRF) confers protection against nutritional challenges that predispose obesity and metabolic risks through involvement of circadian locomotor output cycles protein kaput genes and gut microbiome, but the underlying mechanism is not clearly understood. Therefore, the present study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n 56; non-TRF, n 24) of male adults were enrolled. The TRF group provided blood at pre-TRF and post-TRF, while non-TRF one time after 25 d of trial. Serum lipid and liver profiles were determined. Real time-PCR was applied for circadian and inflammatory gene expression. The 16S rRNA genes were sequenced on the Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In the TRF group, gut microbial richness was significantly enhanced, with enrichment of Prevotellaceae and Bacteroideaceae. TRF enhanced circadian gene expression probably by activation of sirtuin-1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidaemia, as it regulates circadian rhythm associated with gut microbiome modulation.

The identification of natural bioactive compounds which can prevent the post-weaning growth check and enhance gastrointestinal health in the absence of in-feed medications is an urgent priority for the swine industry. The objective of this experiment was to determine the effects of increasing dietary inclusion levels of laminarin in the first 14 d post-weaning on pig growth performance and weaning associated intestinal dysfunction. At weaning, ninety-six pigs (8·4 (sd 1·09) kg) (meatline boars × (large white × landrace sows)) were blocked by live weight, litter and sex and randomly assigned to: (1) basal diet; (2) basal + 100 parts per million (ppm) laminarin; (3) basal + 200 ppm laminarin and (4) basal + 300 ppm laminarin (three pigs/pen). The appropriate quantity of a laminarin-rich extract (65 % laminarin) was added to the basal diet to achieve the above dietary inclusion levels of laminarin. After 14 d of supplementation, eight pigs from the basal group and the best-performing laminarin group were euthanised for sample collection. The 300 ppm laminarin group was selected as this group had higher ADFI compared with all other groups and higher ADG than the basal group (P < 0·05). Laminarin supplementation increased villus height in the duodenum and jejunum (P < 0·05). Laminarin supplementation increased the expression of SLC2A8/GLUT8 in the duodenum, SLC2A2/GLUT2, SLC2A7/GLUT7, SLC15A1/PEPT1 and FABP2 in the jejunum and SLC16A1/MCT1 in the colon. Laminarin supplementation reduced Enterobacteriaceae numbers in the caecum (P < 0·05) and increased lactobacilli numbers (P < 0·05), total volatile fatty acid concentrations and the molar proportions of butyrate (P < 0·01) in the colon. In conclusion, 300 ppm laminarin from a laminarin-rich extract has potential, as a dietary supplement, to improve performance and prevent post-weaning intestinal dysfunction.

Methionine, an essential sulphur-containing amino acid (SAA), plays an integral role in many metabolic processes. Evidence for the methionine requirements of adult dogs is limited, and we employed the indicator amino acid oxidation (IAAO) method to estimate dietary methionine requirements in Labrador retrievers (n 21). Using semi-purified diets, the mean requirement was 0·55 (95 % CI 0·41, 0·71) g/4184 kJ. In a subsequent parallel design study, three groups of adult Labrador retrievers (n 52) were fed semi-purified diets with 0·55 g/4184 kJ (test diet 1), 0·71 g/4184 kJ (test diet 2) or 1·37 g/4184 kJ (control diet) of methionine for 32 weeks to assess the long-term consequences of feeding. The total SAA content (2·68 g/4184 kJ) was maintained through dietary supplementation of cystine. Plasma methionine did not decrease in test group and increased significantly on test diet 1 in weeks 8 and 16 compared with control. Reducing dietary methionine did not have a significant effect on whole blood, plasma or urinary taurine or plasma N-terminal pro B-type natriuretic peptide. Significant effects in both test diets were observed for cholesterol, betaine and dimethylglycine. In conclusion, feeding methionine at the IAAO-estimated mean was sufficient to maintain plasma methionine over 32 weeks when total SAA was maintained. However, choline oxidation may have increased to support plasma methionine and have additional consequences for lipid metabolism. While the IAAO can be employed to assess essential amino acid requirements, such as methionine in the dog using semi-purified diets, further work is required to establish safe levels for commercial diet formats.

The timing of feed intake can alter circadian rhythms of peripheral tissues. Milk synthesis displays a daily rhythm across several species, but the effect of feeding time on these rhythms is poorly characterised. The objective of this experiment was to determine if the time of feed intake modifies the daily patterns of milk synthesis, plasma metabolites and body temperature in dairy cows. Sixteen lactating Holstein dairy cows were randomly assigned to one of the two treatment sequences in a cross-over design with 17 d periods. Treatments included day-restricted feeding (DRF; feed available from 07.00 to 23.00 hours) and night-restricted feeding (NRF; feed available from 19.00 to 11.00 hours). Cows were milked every 6 h on the last 7 d of each period, and blood samples were collected to represent every 4 h over the day. Peak milk yield was shifted from morning in DRF to evening in NRF, while milk fat, protein and lactose concentration peaked in the evening in DRF and the morning in NRF. Plasma glucose, insulin, NEFA and urea nitrogen concentration fit daily rhythms in all treatments. Night feeding increased the amplitude of glucose, insulin and NEFA rhythms and shifted the daily rhythms by 8 to 12 h (P < 0·05). Night feeding also phase-delayed the rhythm of core body temperature and DRF increased its amplitude. Altering the time of feed availability shifts the daily rhythms of milk synthesis and plasma hormone and metabolite concentrations and body temperature, suggesting that these rhythms may be entrained by food intake.

Oral arginine supplements are popular mainly for their presumed vasodilatory benefit. Arginine is a substrate for at least four enzymes including nitric oxide synthase (NOS) and arginase, but the impact of oral supplements on its different metabolic pathways is not clear. Deficiencies of arginine-metabolising enzymes are associated with conditions such as hyperammonaemia, endothelial dysfunction, central nervous system and muscle dysfunction, which complicate the use of oral arginine supplements. We examined the effect of l-arginine (l-Arg) and d-arginine (d-Arg), each at 500 mg/kg per d in drinking water administered for 4 weeks to separate groups of 9-week-old male Sprague–Dawley rats. We quantified the expression of enzymes and plasma, urine and organ levels of various metabolites of arginine. l-Arg significantly decreased cationic transporter-1 expression in the liver and the ileum and increased endothelial NOS expression in the aorta and the kidney and plasma nitrite levels, but did not affect the mean arterial pressure. l-Arg also decreased the expression of arginase II in the ileum, arginine:glycine amidinotransferase in the liver and the kidney and glyoxalase I in the liver, ileum and brain, but increased the expression of arginine decarboxylase and polyamines levels in the liver. d-Arg, the supposedly inert isomer, also unexpectedly affected the expression of some enzymes and metabolites. In conclusion, both l- and d-Arg significantly affected enzymes and metabolites in several pathways that use arginine as a substrate and further studies with different doses and treatment durations are planned to establish their safety or adverse effects to guide their use as oral supplements.

Despite the well-characterised mechanisms of amino acids (AA) regulation of milk protein synthesis in mammary glands (MG), the underlying specific AA regulatory machinery in bovine MG remains further elucidated. As methionine (Met) is one of the most important essential and limiting AA for dairy cows, it is crucial to expand how Met exerts its regulatory effects on dairy milk protein synthesis. Our previous work detected the potential regulatory role of seryl-tRNA synthetase (SARS) in essential AA (EAA)-stimulated bovine casein synthesis. Here, we investigated whether and how SARS participates in Met stimulation of casein production in bovine mammary epithelial cells (BMEC). With or without RNA interference against SARS, BMEC were treated with the medium in the absence (containing all other EAA and devoid of Met alone)/presence (containing 0·6 mm of Met in the medium devoid of Met alone) of Met. The protein abundance of β-casein and members of the mammalian target of rapamycin (mTOR) and general control nonderepressible 2 (GCN2) pathways was determined by immunoblot assay after 6 h treatment, the cell viability and cell cycle progression were determined by cell counting and propidium iodide-staining assay after 24 h treatment, and protein turnover was determined by l-[ring-3H5]phenylalanine isotope tracing assay after 48 h treatment. In the absence of Met, there was a general reduction in cell viability, total protein synthesis and β-casein production; in contrast, total protein degradation was enhanced. SARS knockdown strengthened these changes. Finally, SARS may work to promote Met-stimulated β-casein synthesis via affecting mTOR and GCN2 routes in BMEC.

There is a growing research interest in determining whether changes in the global status of DNA methylation are related to the environment, in particular, to one-carbon metabolism. So, our aim was to investigate the effect of dietary methyl-group donor intake (methionine, folate, choline, betaine, vitamins B2, B6 and B12), biomarkers (total folate, unmetabolised folic acid (FA), 5-methyltetrahydrofolate, homocysteine, vitamins B6 and B12 concentrations) and genetic variants (polymorphisms involved in one-carbon metabolism) on global DNA methylation in a population exposed to mandatory flour fortification with FA. A cross-sectional study of health and living conditions was conducted among a representative sample of residents in São Paulo, Brazil. The mean of global DNA methylation was lower in young people than in adults and the elderly (P = 0·049). No differences between genotypes of polymorphism and global DNA methylation mean were identified. We observed that the increase in betaine intake led to an absolute change in percentage of DNA methylation (β = 0·0005, P = 0·024) using multiple regression. Betaine intake alone was associated with an absolute change in percentage of global DNA methylation. The study did not find an association between global DNA methylation and folate status even in a population exposed to mandatory flour fortification with FA.