Effects of diet-matrix on volatile organic compounds in breath in diet-induced obese mice.

Breath gas analysis in humans proved successful in identifying disease states and assessing metabolic functions in a non-invasive way. While many studies report diagnostic capability using volatile organic compounds (VOC) in breath, the inter-individual variability even in healthy human cohorts is rather large and not completely understood in its biochemical origin. Laboratory mice are the predominant animal model system for human disorders and are analysed under highly standardized and controlled conditions. We established a novel setup to monitor VOCs as biomarkers for disease in the breath gas of non-anesthetized, non-restrained mice using a proton transfer reaction mass spectrometer with time of flight detection. In this study, we implemented breath gas analysis in a dietary intervention study in C57BL/6J mice with the aim to assess the variability in VOC signatures due to a change in the diet matrix. Mice were fed a standard laboratory chow and then exposed to four semi-purified low- or high-fat diets for four weeks. Random forest (RF++) was used to identify VOCs that specifically respond to the diet matrix change. Interestingly, we found that the change from a chow diet to semi-purified diets resulted in a considerable drop of several VOC levels. Our results suggest that the diet matrix impacts VOC signatures and the underlying metabolic functions and may be one source of variability in exhaled volatiles.

Enhanced peroxisomal ß-oxidation is associated with prevention of obesity and glucose intolerance by fish oil-enriched diets.

OBJECTIVE: The effects of different amounts of omega 3-polyunsaturated fatty acids in diets with normal or high content of fat on lipid and carbohydrate metabolism were investigated. DESIGN AND METHODS: Mice were fed for 8 weeks on diets enriched with fish oil or lard at 10% or 60% of energy. Energy balance and energy expenditure were analyzed. Fatty acid (FA) oxidative capacity of the liver and the activity of enzymes involved in this pathway were assessed. RESULTS: Fish oil-fed mice had lower body weight and adiposity compared with lard-fed animals, despite having lower rates of oxygen consumption. Mice fed diets containing fish oil also displayed lower glycemia, reduced fat content in the liver, and improved glucose tolerance compared with lard-fed animals. The fish oil-containing diets increased markers of hepatic peroxisomal content and increased the generation of metabolites derived from FA ß-oxidation in liver homogenates. In contrast, no changes were observed in the content of mitochondrial electron transport chain proteins or carnitine palmitoyl transferase-1 in the liver, indicating little direct effect of fish oil on mitochondrial metabolism. CONCLUSION: Collectively, our findings suggest that the energy inefficient oxidation of FAs in peroxisomes may be an important mechanism underlying the protection against obesity and glucose intolerance of fish oil administration.

Changes in food intake, metabolic parameters and insulin resistance are induced by an isoenergetic, medium-chain fatty acid diet and are associated with modifications in insulin signalling in isolated rat pancreatic islets.

Long-chain fatty acids are capable of inducing alterations in the homoeostasis of glucose-stimulated insulin secretion (GSIS), but the effect of medium-chain fatty acids (MCFA) is poorly elucidated. In the present study, we fed a normoenergetic MCFA diet to male rats from the age of 1 month to the age of 4 months in order to analyse the effect of MCFA on body growth, insulin sensitivity and GSIS. The 45% MCFA substitution of whole fatty acids in the normoenergetic diet impaired whole body growth and resulted in increased body adiposity and hyperinsulinaemia, and reduced insulin-mediated glucose uptake in skeletal muscle. In addition, the isolated pancreatic islets from the MCFA-fed rats showed impaired GSIS and reduced protein kinase Ba (AKT1) protein expression and extracellular signal-related kinase isoforms 1 and 2 (ERK(1/2)) phosphorylation, which were accompanied by increased cellular death. Furthermore, there was a mildly increased cholinergic sensitivity to GSIS. We discuss these findings in further detail, and advocate that they might have a role in the mechanistic pathway leading to the compensatory hyperinsulinaemic status found in this animal model.

Effect of medium/ω-6 long chain triglyceride-based emulsion on leucocyte death and inflammatory gene expression.

Lipid emulsion (LE) containing medium/ω-6 long chain triglyceride-based emulsion (MCT/ω-6 LCT LE) has been recommended in the place of ω-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/ω-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/ω-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/ω-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/ω-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription.

Comparison of fatty acid composition in nine organs of the sympatric Antarctic teleost fish species Notothenia coriiceps and Notothenia rossii (Perciformes: Nototheniidae).

Fatty acid (FA) composition of nine organs from two closely related Antarctic fish species, Notothenia coriiceps and Notothenia rossii, was determined through gas chromatography with flame ionization detection. A data set for each species was obtained using major FA profiles from specimens caught in the sea waters of Admiralty Bay during the summer season. The FA profiles for both species are overall similar, but organ peculiarities have been found, which could reflect metabolic specificities and feeding habits between species. With the exception of liver, the most abundant FA in organs was the n-3 polyunsaturated FA. The total n-6 polyunsaturated FAs were minor components in all evaluated organs. Palmitic acid was identified as the major saturated FA, whereas oleic acid was the most represented of the monounsaturated FA in almost all assessed organs of both species. The n-3/n-6 ratios of all organs were higher than 3.5. Differences in individual FA and FA metabolic profiles of some organs observed between N. coriiceps and N. rossii suggest specific requirements in the mobilization, transport, incorporation, and/or catabolism of lipids that were reinforced by differences on some FA ratios expressing the activity coefficient of enzymes implicated on the FA pathway flux.