Zinc deficiency affects hepatic functions and due to the central role of the liver in metabolism, this may contribute to metabolic alterations in other tissues in zinc deficiency. In addition to clinical manifestations of zinc deficiency, we used cDNA- and oligonucleotide-arrays to compare the expression of > 2500 different genes in liver of rats force-fed a zinc-adequate or a zinc-deficient diet for 11 d. Radio- or fluorescence-labeled cDNAs from liver of control and zinc-deficient rats were hybridized to arrays. Approximately 1550 mRNAs were detected above background levels; by comparing expression profiles of the two groups, the mRNA levels of 66 genes were found to be altered by zinc deficiency. Steady-state expression levels of 35 genes were reduced, whereas the mRNA-levels of 31 genes were elevated. Array data were verified by Northern blot analysis for 24 selected genes and 19 were confirmed to be up- or down-regulated. Among those, predominantly gene products that participate in growth (i.e., insulin-like growth factor binding proteins), lipid metabolism (long-chain acyl-CoA synthetase), xenobiotic metabolism (cytochrome P(450) isoenzymes), the stress response (glutathione transferase), nitrogen metabolism (cytosolic aspartate aminotransferase), intracellular trafficking (syntaxin isoforms) and signal transduction (G-protein-coupled receptors) were identified. Additionally, regulation of mRNA levels of genes important for porphyrin synthesis and collagen metabolism was observed. In conclusion, we have identified in vivo a number of mammalian genes from different cellular pathways whose expression changes in response to zinc depletion. The characterization of the identified genes and their products will allow a more comprehensive analysis of the role of zinc in metabolism; moreover, the mRNAs identified could be useful in establishing biomarkers for the determination of zinc status in mammals.

For identification of the underlying molecular changes in hepatic lipid metabolism in zinc deficiency, rats were force-fed a zinc-deficient diet. Subsequently DNA-microarray and proteome profiling was performed in combination with hepatic lipid analysis. Of 6200 target sequences analyzed, 268 transcripts showed altered expression levels in livers of zinc-deficient rats, with 43 genes thereof related to hepatic lipid metabolism. Northern blot analysis and quantitative real-time RT-PCR were employed to confirm changes in mRNA levels. Proteins involved in lipid metabolism were identified by proteome analysis. Functional gene clusters with uniform changes in transcript levels suggested that the pathways required for lipolysis and mitochondrial as well as peroxisomal fatty acid degradation were downregulated, whereas those needed for de novo fatty acid synthesis and triglyceride assembly were increased. Subsequent enzymatic analysis of liver tissues confirmed an almost 40% greater triacylglycerol concentration in zinc-depleted rats, as well as an altered fatty acid composition of the lipid fraction as determined by gas chromatography. Liver lipids of zinc-deficient rats had significantly greater proportions of cis-9-oleic acid, cis-11-vaccenic acid, caprylic acid, myristic acid, alpha-linolenic acid, and eicosapentaenoic acid, and significantly less stearic and arachidonic acids. These alterations in hepatic metabolism are discussed in the context of changes in mRNA and protein levels of enzymes and transporters responsible for fatty acid metabolism, sequestration, and their transcriptional control.

Subjects with obesity and elevated fasting blood glucose are at high risk of developing type 2 diabetes which may be reduced by a dietary intervention leading to an improvement of insulin resistance. We investigated the potential of a whole-grain based dietary product (WG) with reduced starch content derived from double-fermented wheat during a hypo-energetic diet to positively influence body weight, fasting blood glucose, insulin resistance and lipids in comparison to a nutrient-dense meal replacement product (MR) in a randomized two-way cross-over study with two 4-week treatment periods separated by a 2-week wash-out. Subjects replaced at least two daily meals with WG and MR, respectively, targeting for a consumption of 200 g of either product per day. Total daily energy intake was limited to 7120 kJ. Thirty-one subjects (BMI 33·9 (SD 2·7) kg/m 2 , fasting blood glucose 6·3 (SD 0·8) mmol/l) completed the study. In both treatment groups body weight (22·5 (SD 2·0) v. 2 3·2 (SD 1·6) kg for WG v. MR), fasting blood glucose (2 0·4 (SD 0·3) v. 20·5 (SD 0·5) mmol/l), total cholesterol (20·5 (SD 0·5) v. 2 0·6 (SD 0·5) mmol/l), TAG (2 0·3 (SD 0·9) v. 2 0·3 (SD 1·2) mmol/l) and homeostasis model assessment (HOMA) insulin resistance score (20·7 (SD 0·8) v. 21·1 (SD 1·7) mU/ml £ mmol/l) improved (P,0·05) with no significant differences between the treatments. After statistical adjustment for the amount of body weight lost, however, the comparison between both groups revealed that fasting serum insulin (P¼ 0·031) and HOMA insulin resistance score (P¼ 0·049) improved better with WG than with MR. We conclude that WG favourably influences metabolic risk factors for type 2 diabetes independent from the amount of body weight lost during a hypo-energetic diet.Dietary fibre: Insulin resistance: Type 2 diabetes: Whole grain Type 2 diabetes and its long-term complications are a major cause of morbidity and mortality worldwide and the prevalence of the disease continues to rise 1,2 . The increasing incidence of type 2 diabetes is associated with increasing rates of obesity in most countries 3 . Obesity, in turn, is often associated with insulin resistance which is considered as one of the underlying causes of diabetes 4 . Thus, a dietary therapy capable of achieving both weight reduction and improvement of insulin resistance may potentially reduce the incidence of type 2 diabetes in obese subjects prone to develop the disease.Special attention has been focused on carbohydrates in nutrition. Carbohydrates have the greatest influence on postprandial glucose excursions and are the primary stimulus for postprandial insulin release, thus being directly associated with insulin resistance 5 . In Western countries the consumption of cereals constitutes the main source of dietary carbohydrates 6 . Cereals are mostly consumed as highly processed products which have lost a substantial amount of dietary fibre and contain a relatively high concentration of starch because most of the bran and germ is removed in the refining process. In contrast, ...

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.

Based on the effects of a selective experimental zinc deficiency in a rodent model we explore the use of transcriptome profiling for assessing nutrient-gene interactions in the liver at the molecular and cellular levels. Zinc deficiency caused pleiotropic alterations in mRNA/protein levels of hundreds of genes. In the context of observed metabolic alterations in hepatic metabolism, possible mechanisms are discussed for how a low zinc status may be sensed and transmitted into changes in various metabolic pathways. However, it also becomes obvious that analysis of such complex nutrient-gene interactions beyond the descriptional level is a real challenge for systems biology.