It is inconclusive whether trimethylamine N-oxide (TMAO) and choline and related metabolites, namely trimethylamine (TMA), l-carnitine, betaine and dimethylglycine (DMG), are associated with non-alcoholic fatty liver disease (NAFLD). Our objective was to investigate these potential associations. Additionally, we sought to determine the mediating role of TMAO. In this 1:1 age- and sex-matched case–control study, a total of 150 pairs comprising NAFLD cases and healthy controls were identified. According to the fully adjusted model, after the highest tertile was compared with the lowest tertile, the plasma TMAO concentration (OR = 2·02 (95 % CI 1·04, 3·92); P trend = 0·003), l-carnitine concentration (OR = 1·79 (1·01, 3·17); P trend = 0·020) and DMG concentration (OR = 1·81 (1·00, 3·28); P trend = 0·014) were significantly positively associated with NAFLD incidence. However, a significantly negative association was found for plasma betaine (OR = 0. 50 (0·28, 0·88); P trend = 0·001). The restricted cubic splines model consistently indicated positive dose–response relationships between exposure to TMAO, l-carnitine, and DMG and NAFLD risk, with a negative association being observed for betaine. The corresponding AUC increased significantly from 0·685 (0·626, 0·745) in the traditional risk factor model to 0·769 (0·716, 0·822) when TMAO and its precursors were included (l-carnitine, betaine and choline) (P = 0·032). Mediation analyses revealed that 14·7 and 18·6 % of the excess NAFLD risk associated with l-carnitine and DMG, respectively, was mediated by TMAO (the P values for the mediating effects were 0·021 and 0·036, respectively). These results suggest that a higher concentration of TMAO is associated with increased NAFLD risk among Chinese adults and provide evidence of the possible mediating role of TMAO.

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.

In the present study we have developed the agar-fill method for the measurement of gastrointestinal-tract capacity (GTC) to replace the in vitro water-fill method. This would estimate GTC without using complex equipment and techniques, and can be applied to the measurement of GTC for small laboratory animals. We attempted to confirm the efficiency of the agar-fill method by investigating the relationship between dietary neutral-detergent fibre (NDF) content and GTC. The digestion trials were carried out using the Syrian hamster (Mesocricefus auretus). The trials were conducted using both sexes, two age-groups and three levels of dietary NDF with a cross-classified design. The size of each gastrointestinal organ was determined as tissue weight(TW)and GTC. The DM intake, digestible DM intake, DM digestibility, NDF digestibfity, aciddetergent fibre(ADF) digestibfity and digesta transit time were also measured. GTC increased with increasing NDF content of the diets. TW responded similarly to increasing NDF content, but the response was smaller than that of GTC. DM digestibility decreased with increasing NDF content of the diet. The digestible DM intake did not decrease with increasing NDF because DM intake increased with NDF content. Digesta transit time was not shorter of the high-NDF-diet group but DM intake increased with increasing NDF content. NDF digestibility did not differ significantly between low- and medium-NDF diets. ADF digestibility was low in the low-NDF-diet group.The digestion characteristics were highly correlated with TW and GTC, except for TW of small intestine. These correlations were higher with GTC than with TW. The results of the present study confirm previous findings suggesting that the agar-fill method is a useful means of estimating GTC for small laboratory animals.

An experiment was conducted in the pig to determine the consequences of deprivation of exocrine pancreatic secretion on the composition and quantity of nutrients absorbed after intake of a balanced diet. Five growing pigs (53·8 kg body weight) were fitted with permanent catheters in the portal vein and the carotid artery and with an electromagnetic flow probe around the portal vein to measure the exchanges between the blood and the intestinal lumen. They were also fitted with a permanent catheter in the duct of Wirsung to educe the exocrine pancreatic secretion and another one in the duodenum in order to reintroduce it. In each animal, glucose, amino-N and amino acid absorption as well as insulin and glucagon production were measured over a period of 10 h after the meal (semi-purified diet based on purified starch and containing 180 g fish meal/kg, DM content of the meal 731 g), either in the presence of pancreatic juice (group C : immediate reintroduction), or in the absence of pancreatic juice (group D: deprivation). The deprivation of pancreatic juice provoked a marked depression in the absorption of glucose (D 67·9 (SEM 27·9) g/10 h, C 437·7 (SEM 39·5) g/10 h, P < 0·00l), and of amino-N (D 7·55 (SEM 0·54) g/10 h, C 15·80 (SEM 0·79) g/10 h, P < 0·001). The composition of the mixture of amino acids in the portal blood was only slightly modified: only the levels of histidine (P < 0·05) and of valine (P < 0·06, NS) decreased in the absence of pancreatic juice. Insulin production was much lower (by 64%, P < 0·05) in the absence of pancreatic juice whereas that of glucagon was not affected.

Urinary Na excretion is a potential risk factor for CVD. However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterise the relative contribution of biological factors to the Na–CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour Na excretion was estimated using a single overnight urine sample. Hypertension, the metabolic syndrome and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary Na excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (sd) of the 2112 participants was 54·5 (sd 12·2) years, and they were followed up for a mean of 14·1 (sd 8·1) years. Compared with those in the lowest quartile, the highest baseline urinary Na excretion (>4·2 g/24 h) was associated with a 43 % higher CVD risk (hazard ratio, 1·43; 95 % CI 1·02, 1·99). Participants with high urinary Na excretion, hypertension or the metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35 % of the Na–CVD association), followed by systolic blood pressure (BP) (33 %), left ventricular mass (28 %) and diastolic BP (14 %). Higher urinary Na excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic BP.

1. The vascular anatomy of the bovine omasal lamina permitted perfusion of a discrete area of the tissue. As occurs in vivo, oxygen was provided through the vascular system, while the luminal sides of the tissue could be kept in an anaerobic environment, thus allowing study of foregut tissue metabolism under physiologically realistic conditions.

2. O2 consumption of perfused leaves in the presence of anaerobic buffer was 64.9 and 73.5 nmol O2/mg dry weight per h in Expts 1 and 2 respectively, and was elevated (P < 0.05) when the lumen side of the tissue was exposed to an atmosphere of nitrogen gas.

3. In Expt 1, the rate of O2 consumption was increased (P < 0.01) by 35% as a result of suspension of a boiled preparation of rumen micro-organisms and particles (< 1 mm) in the anaerobic lumen buffer. Replacement of the boiled preparation with an unboiled suspension increased O2 consumption further by 11 %, but this was not statistically significant (P > 0.05).

4. In Expt 2, sequential addition of the following substrates or preparations to the lumen chambers all resulted in stepwise increases (P < 0.05) in O2 consumption; 8 mM-butyrate, boiled rumen micro-organisms and particles and, finally, unboiled rumen micro-organisms and particles.

5. Identities of the heat-labile and heat-stable components of the microbial and particle suspensions that caused enhancement of O2 removal across the perfused tissue are discussed.