Changes in tissue composition and protein synthesis ratio were studied in the major tissues of the body in young rats fed on lipid-rich, isonitrogenous purified liquid diets, a convenient method for inducing voluntary overfeeding under controlled nutritional conditions. Overfed rats showed faster growth induced by the energy excess. Analysis of tissue composition (protein, DNA and RNA contents) revealed that growth was due mainly to tissue hyperplasia in which protein and DNA contents increased in parallel. Fractional protein synthesis ratio measured in vivo by the flooding-dose method of phenylalanine showed a marked increase in all tissues. This change could be attributed to an increase in the ribosomal activity for protein synthesis in most tissues. Therefore, our results indicate that addition of a supplementary energy source (as lipids) to a well-balanced diet improves growth and protein synthesis in growing rats.

Follow-up modalities for adult coeliac patients remain controversial. Non-invasive markers to identify coeliac patients on a gluten-free diet (GFD) with persistence of villous atrophy (VA) are still lacking. We aim to develop a score to stratify coeliac patients on a GFD according to their risk of having persistent VA and to tailor follow-up modalities accordingly. The clinical notes of over 700 coeliac patients attending our unit (September 1999–November 2018) were retrospectively examined. A total of 273 patients on a GFD with a histological follow-up performed 12–24 months after diagnosis were selected. We developed a bivariable model based on diet adherence and clinical response evaluated by previously validated methods. A four-level score (0·5, 1·5, 3, 4) was obtained. Patients on a strict GFD and with good clinical conditions (score 4) have a very low risk of persistence of VA (2 (95 % CI 1, 5) %). Conversely, the risk is very high (46 (95 % CI 25, 68) %) in patients with poor adherence to a GFD and unsatisfactory clinical response (score 0·5). A score of 1·5 (poor GFD adherence and persistent well-being) is linked with a high risk (23 (95 % CI 14, 36) %). Risk is intermediate (6 (95 % CI 3, 10) %) in patients scoring 3 (strict GFD and no/partial clinical improvement). Three patients who developed complications belonged to this scenario. Patients at low risk of persistent VA can be followed-up non-invasively, whereas a biopsy should be repeated in those at high/very high risk. Case-by-case evaluation is needed in patients at intermediate risk. Studies on a larger sample size are required to confirm these data.

Sprague–Dawley rats were fed for 4 months on a control diet or a polyunsaturated-fatty-acid (PUFA)-deficient diet. The combined effects of iron overload (Fe dextran) or Fe deficiency (desferrioxamine) on carrageenan-induced granuloma were studied. PUFA deficiency induced changes in Fe metabolism, but no alterations in lipid peroxidation variables were observed. Inflammation implied an increase in lipid peroxidation, Fe storage and caeruloplasmin concentration, together with symptoms of anaemia. PUFA deficiency in inflamed rats gave rise to a lower inflammatory response (granuloma weight and prostaglandin E2 concentration) and ethane exhalation. Fe overload potentiated inflammatory and lipid peroxidation processes, whereas Fe deficiency decreased them.

Male Wistar rats (188 g) were fed on a semi-synthetic (SS) diet (38 mg iron/kg) ad lib. for 7 d and then meal-fed for 1 d. After a 21 h fast each rat was given one meal (10 g) of high-Fe SS (500 mg Fe/kg; high-Fe group) or control (38 mg Fe/kg; control group) diet. After 16 h 2 ml of an 59Fe-labelled ferrous sulphate solution (18 kBq 59Fe; 120 μg Fe) was administrated by gavage and equal numbers of rats from each group were killed 6 or 24 h after dosing. Mucosal uptake of 59Fe from the gut lumen and transfer of 59Fe from mucosa into the carcass were measured. Total Fe content of the duodenum was also determined. Mucosal 59Fe uptake and transfer were markedly lower in the high-Fe group compared with the control group. The Fe content of the duodenum, the major region of Fe absorption, was significantly greater in the high-Fe group than in the controls. A larger amount of Fe may thus have been released into the lumen of the high-Fe rats, via mucosal cell turnover, resulting in a greater lumen dilution of the 59Fe dose in this group compared with the controls. Calculations are presented which demonstrate that such an effect could not possibly account for the observed difference in mucosal 59Fe uptake between groups. Differences in rates of ‘cold’ Fe and 59Fe loss from the duodenal mucosa during the 6–24 h interval suggested that, at the time of dosing, Fe retained in the mucosa from the previous meal had been incorporated into a non-exchangeable pool and as such would not dilute radioactive Fe entering the mucosa. It was concluded that whole-body 59Fe retention from a labelled source, given orally after an overnight fast, provided an accurate estimate of Fe absorption.

From days 4–104 of pregnancy, adolescent sheep, weighing 43·7 (SE 0·87)kg were offered a complete diet at two different intakes (approximately 5 or 15 kg/week) designed to meet slightly, or well above, maternal maintenance requirements. The fetal and maternal muscles were taken on day 104 of pregnancy and analysed for total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal weight gain, weighed more (76·5 (SE 4·5) v. 50·0 (SE 1·7) kg) and had muscles with a greater fresh weight, whilst their fetuses had smaller muscles, than those fed at a lower intake. Plantaris muscle of the ewes fed at the high intake contained more RNA and protein; again the opposite situation was found in the fetal muscle. On the higher maternal intakes, the DNA, RNA and protein contents of the fetal plantaris muscle were less than in fetuses of ewes fed at the lower intake. To investigate the possible mechanisms involved in this decrease in fetal muscle mass, cytosolic and membrane-associated muscle proteins were subjected to Western immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a family of enzymes known to play an important role in cell growth. Five PKC isoforms (α, ε, θ, μ and ζ) were identified in fetal muscle. One of these, PKC-α, was located predominantly in the cytosolic compartment in the smaller fetuses of the ewes fed at a high plane of nutrition, but was present to a greater extent in the membranes of the more rapidly growing fetuses of the ewes fed at the lower intake. This was the only isoform to demonstrate nutritionally related changes in its subcellular compartmentation suggesting that it may mediate some aspects of the change in fetal growth rate.

Cryptomys hottentotus has no access to dietary or endogenous sources of cholecalciferol (D3). Serum concentrations of calcifediol (25(OH)D3) were undetectable (< 5 ng/ml) and calcitriol (1,25(OH)2D3), although detectable in plasma, was at a low concentration (31.40) (SEM 3.06 pg/ml). Despite their naturally impoverished vitamin D status, these animals exhibited highly efficient mineral absorption processes (Ca apparent fractional absorption efficiency, AFA (%) 95.33 (SEM 1.36); inorganic P (Pi) AFA (%) 93.49 (SEM 0.81)). Furthermore, plasma mineral content was tightly regulated (Ca 2.57 (SEM 0.08) mmol/l; Mg 1.23 (SEM 0.05) mmol/l; Pi 2.12 (SEM 0.15) mmol/1). Mode of uptake in C. hottentotus was unlike that in other D3-replete mammals. First, passive (rather than active) uptake occurred in the traditional site of active Ca absorption (with serosal: mucosal (S:M) ratios in the duodenum of 1.32 (SEM 0.13)), and the only site of active Ca uptake was the hindgut (caecum S:M 3.35 (SEM 0.46); proximal colon S:M 2.13 (SEM 0.30)). Despite the presence of active uptake in these hindgut regions, their overall contribution to the daily rate of mineral absorption was small (9.53 (SEM 1.27)%). These underground inhabitants rely upon highly efficient, passive mineral uptake. This is adequate to meet their mineral requirements and maintain mineral homeostasis in the absence of vitamin D.

Misalignment of day/night and feeding rhythms has been shown to increase fat deposition and the risk for metabolic disorders in humans and rodents. In most studies, however, food intake and intake patterns are not controlled. We studied the effects of circadian misalignment on energy expenditure in pigs while controlling for food intake as well as intake patterns. Twelve groups of five male pigs were housed in respiration chambers and fed either during the day (10.00–18.00 hours; DF) or night (22.00–06.00 hours; NF), bihourly the same sequential meals, representing 15, 10, 25, 30 and 20 % of the daily allowance. Paired feeding was applied to ensure equal gross energy intake between treatments. Apparent total tract digestibility, energy balances and heat partitioning were measured and analysed using a mixed linear model. Apparent total tract energy and DM digestibility tended to be lower for NF-pigs than DF-pigs (P < 0·10). Heat production was 3 % lower for NF-pigs than DF-pigs (P < 0·026), increasing fat retention by 7 % in NF-pigs (P = 0·050). NF-pigs were less active than DF-pigs during the feeding period, but more active during the fasting period. RMR was greater for DF-pigs than NF-pigs during the fasting period. Methane production was 30 % greater in NF-pigs than DF-pigs (P < 0·001). In conclusion, circadian misalignment has little effect on nutrient digestion, but alters nutrient partitioning, ultimately increasing fat deposition. The causality of the association between circadian misalignment and methane production rates remains to be investigated.

The declining inflammatory immune competence of acute (i.e. wasting) pre-pubescent protein–energy malnutrition has been regarded as reflecting an unregulated immunological disintegration. Recent evidence, however, suggests that malnutrition stimulates a regulated immunological reconfiguration to achieve a non-inflammatory form of competence, perhaps offering protection against autoimmune reactions – the ‘Tolerance Model’. Our objective was to determine the influence of acute pre-pubescent malnutrition on the expression of genes critical to tolerogenic regulation. Male and female C57BL/6J mice, initially 19 d old, consumed a complete purified diet either ad libitum (age-matched controls) or in restricted daily quantities (mimicking marasmus), or consumed an isoenergetic low-protein diet ad libitum (mimicking incipient kwashiorkor) for 14 d (six animals per dietary group). Gene expression in the spleen, typically an inflammatory organ, and in the small intestine, a site designed for non-inflammatory defence, was assessed by real-time quantitative RT-PCR, and normalised to β-actin. In the spleen of the malnourished groups, both IL-10 and transforming growth factor-β1 mRNA expression increased compared with controls (P < 0·05), whereas mRNA expression of IL-12p40 decreased (P < 0·05). Conversely, malnutrition exerted no influence on the expression of mRNA for these cytokines in the small intestine (P>0·05). Moreover, forkhead box P3 mRNA expression, indicative of cell-based tolerogenic potential, was sustained in both the spleen and intestine of the malnourished groups (P>0·05). Thus, despite limited supplies of energy and substrates, the spleen shifted towards a non-inflammatory character and the intestine was sustained in this mode in advanced pre-pubescent weight loss. These findings provide the first support for the Tolerance Model at the level of mRNA transcript expression.

The objective of the present study was to investigate the influence of the single nucleotide polymorphism (rs17238540) at the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (HMGCR) on the relationship between serum lipids and dietary fat and fibre (NSP). FFQ and pyrosequencing were used to assess cross-sectional dietary intake and HMGCR genotype in a population study with data for serum lipids available. Genotype frequencies and allele distributions for 23 011 participants were: TT 95·65 %, TG 4·29 % and GG 0·06 %; T 97·8 % and G 2·2 %. In regression analyses, the TG+GG group showed a significant positive relationship between TAG and SFA intake (+0·11 (95 % CI 0·02, 0·20) mmol TAG/l; P = 0·017; per 3 % SFA energy increase) while the TT individuals showed no change in the TAG levels related to SFA intake ( − 0·0007 (95 % CI − 0·02, 0·02) mmol TAG/l; P = 0·99). TG+GG individuals showed an inverse relationship between TAG and fibre intake higher ( − 0·14 (95 % CI − 0·22, − 0·05) mmol TAG/l than the TT group ( − 0·04 (95 % CI − 0·06, − 0·02) mmol TAG/l). In both cases the respective coefficient regressions of TAG were different between the genotype groups (Z = 2·27, P = 0·023 for SFA intake; Z = 2·19, P = 0·029 for fibre intake). Individuals carrying the G allele may show a greater response in lower TAG levels with reduced SFA intake and increased fibre intake compared with those homozygous for the T allele. The effectiveness of different dietary interventions to control serum lipids may vary according to HMGCR genotype.

The beneficial effects of a low-glycaemic index (GI) meal on postprandial glucose and insulin levels have been demonstrated. However, limited data are available on the impact of overweight and glucose tolerance on postprandial responses to different GI meals. Our aim was to study the effects of physiological characteristics on postprandial glucose, insulin and lipid responses and the relative glycaemic response (RGR) of a low-GI (LGI) and a high-GI (HGI) meal. We recruited twenty-four normal-weight and twenty-four overweight subjects, twelve with normal glucose tolerance (NGT) and twelve with impaired glucose tolerance (IGT) in each group. Both test meals were consumed once and the glucose reference twice. Blood glucose and insulin were measured in the fasting state and over a 2 h period after each study meal, and TAG and NEFA were measured in the fasting state and over a 5 h period. The glucose responses of subjects with IGT differed significantly from those of subjects with NGT. The highest insulin responses to both meals were observed in overweight subjects with IGT. Physiological characteristics did not influence TAG or NEFA responses or the RGR of the meals. The LGI meal resulted in lower glucose (P < 0·001) and insulin (P < 0·001) responses, but higher TAG responses (P < 0·001), compared with the HGI meal. The GI of the meals did not affect the NEFA responses. In conclusion, the LGI meal causes lower glucose and insulin responses, but higher TAG responses, than the HGI meal. The RGR of the meals does not differ between normal-weight and overweight subjects with NGT or IGT.

Folates, an essential component (important B vitamin) in the human diet, are involved in many metabolic pathways, mainly in carbon transfer reactions such as purine and pyrimidine biosynthesis and amino acid interconversions. Deficiency of this micronutrient leads to the disruption of folate-dependent metabolic pathways that lead to the development of clinical abnormalities ranging from anaemia to growth retardation. Folate deficiency due to alcohol ingestion is quite common, primarily due to malabsorption. The present study dealt with the mechanistic insights of folate malabsorption in colonic basolateral membrane (BLM). Wistar rats (n 12) were fed 1 g/kg body weight per d ethanol (20 %) solution orally for 3 months and folate transport was studied in the isolated colonic BLM. The folate exit across colon BLM shows characteristics of carrier-mediated process with the major involvement of reduced folate carrier (RFC). The chronic ethanol ingestion decreased the uptake by decreasing the affinity by 46 % (P < 0·01) and the number of transport molecules by 43 % (P < 0·001) at the colon BLM. The decreased uptake was associated with down-regulation of proton-coupled folate transporter (PCFT) and RFC expression at mRNA and protein levels. The extent of decrease was 44 % (P < 0·01) and 24 % (P < 0·05) for PCFT and 23 % (P < 0·01) and 57 % (P < 0·01) for RFC at mRNA and protein levels, respectively. Moreover, folate transporters were associated with lipid rafts (LR) of colon BLM, and chronic alcoholism decreased the association of these transporters with LR.

Type of feeding during early life influences growth trajectory and metabolic risk at later ages. Modifications in infant formula composition have led to evaluate their effects on growth and energetic efficiency (EE) compared with breast-feeding. Main goal was to analyse type of feeding potential effects during first months of life, plus its EE, on growth patterns in healthy formula fed (standard infant formula (SF) vs. experimental infant formula enriched with bioactive nutrients (EF)) and breastfed (BF) infants participating in the COGNIS RCT (http://www.ClinicalTrials.gov, Identifier: NCT02094547) up to 18 months of age. Infants follow-up to 18 months of age (n 141) fed with a SF (n 48), EF(n 56), or BF (n 37), were assessed for growth parameters using WHO standards. Growth velocity (GV) and catch-up were calculated to identify growth patterns. EE of breast milk/infant formula was also estimated. Infants’ growth at 6 months showed higher length and lower head circumference gains in SF and EF infants than BF infants. Both weight-for-length and weight-for-age catch-up growth showed significant differences in formula fed groups compared with the BF. No significant differences in GV or catch-up were found at 6–12 and 12–18 months. Regarding EE, infant formula groups showed significantly lower weight and length gains/g of milk protein, and higher weight and length gains/g of milk lipids, than the BF infants. GV during first 6 months, which may be influenced by feeding, seems to be the main predictor of subsequent growth trajectory. Breast-feeding may have positive effects on growth programming due to its nutrients’ EE.

1. The effects of vitamin D3 (D3) on serum levels of 1, 25-dihydroxyvitamin D3 (1, 25(OH)2D3), ionic calcium, total Ca and phosphorus in chicks were studied from the time of hatching until sexual maturity.

2. Chicks fed on a diet low in D3 showed a serum level of 1, 25(OH)2D3 higher than that in chicks on a normal-D3 diet, for both sexes and at any given age.

3. A dramatic increase in the serum level of 1, 25(OH)2D3 occurred in female birds approaching sexual maturity and in laying hens raised on the low-D3 diet the level was five times that of their counterparts raised on a normal-D3 diet.

4. Theserum 1, 25(OH)2D3levelin adultmalesin thelow-D3groups wasseven timesthatofthoseon thenormal-D3 diet.

5. The serum level of 25-hydroxyvitamin D3 remained relatively unchanged at weeks 2 and 15 in birds on a low D3 intake as well as in those fed on a normal-D3 diet. Nevertheless, the levels of 25-hydroxyvitamin D3 were different between the two groups.

6. No significant change was observed in the level of ionized serum Ca in relation to dietary regimen, but there was an increase in total Ca concentration in females with the onset of reproduction.

7. The serum P level decreased gradually with age, reaching a minimum value 3 and 8 weeks before laying commenced in the groups on low- and normal-D3 diets respectively. An increase was observed when the hens began laying.

8. Chicks adapted to a low-D3 diet by elevation of their plasma level of 1, 25(OH)2D3. The mechanism by which this is achieved is not known, but the results suggest that parathyroid hormone, Ca and P are unlikely to play roles in the adaptive increase in the level of 1, 25(OH)2D3 in the blood of chicks given a minimal amount of D3. The possibility that the rate of degradation of 1, 25(OH)2D3 is greatly reduced under these conditions cannot be excluded and this could account for the level of this metabolite in those birds.

1. The changes in serum lipid and protein concentrations, and in carbohydrate tolerance were studied in eleven young male volunteers during a 3-week period of either nibbling or gorging a diet containing a high proportion of sucrose.

2. It was found that when gorging, the serum glyceride concentration rose early in the dietary period and reached a plateau, that the serum albumin concentration fell and that the glucose tolerance remained unchanged, although there was evidence for an increased rate of absorption of glucose.

3. On the nibbling regime, the serum glyceride concentration rose progressively over the 3-week period, the serum phospholipid concentration fell significantly and the serum albumin concentration fell but to a lesser degree than when gorging.

4. The glucose tolerance was improved when nibbling, and again there was evidence for an increased absorption of glucose.

5. An attempt is made to interrelate these findings.

Inadequate Ca intakes are a concern for global public health. In France, most dietary Ca is provided by dairy products: milks, fermented milks (mostly yogurts), dairy desserts and cheeses. The present dairy database (n 837) included milks (n 101), fermented milks, yogurts and other fresh dairy products (n 326), desserts (n 162) and a wide variety of cheeses (n 248). Energy and nutrient values were obtained from industry sources and the French national nutrient composition database. Retail prices were from Paris supermarkets. Products in each group were aggregated into twenty-one categories using clustering analyses. The costs in energy (kJ (kcal)), euros (€), and in SFA, added sugar and Na (defined here as nutrients to LIMit) associated with providing 120 mg of Ca (equivalent to 15 % daily value (15 % DV)) were calculated for each product group and category. The milk group supplied Ca at the lowest energy, monetary and LIM cost. Fresh plain and ‘light’ yogurts and fermented milks were next, followed by sweetened yogurts and flavoured milks. Light dairy desserts provided Ca with relatively few energy but were more expensive. Cheeses were a heterogeneous group. Hard cheeses (Comté) provided the most Ca per serving. Semi-hard cheeses (Camembert) and cream and blue cheeses (Roquefort) provided Ca at a cost comparable with sweetened yogurts and flavoured milks. Double cream, soft and goat cheeses were not optimal Ca sources. New value metrics can help identify affordable dairy foods that provide Ca without excessive energy or nutrients to limit. These conditions were satisfied by a wide variety of dairy products in France.