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A high fat, high cholesterol diet leads to changes in metabolite patterns in pigs--a metabolomic study.

ABSTRACT: Non-targeted metabolite profiling can identify biological markers of dietary exposure that lead to a better understanding of interactions between diet and health. In this study, pigs were used as an animal model to discover changes in metabolic profiles between regular basal and high fat/high cholesterol diets. Extracts of plasma, fecal and urine samples from pigs fed high fat or basal regular diets for 11 weeks were analysed using ultra-high performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS) and chemometric analysis. Cloud plots from XCMS online were used for class separation of the most discriminatory metabolites. The major metabolites contributing to the discrimination were identified as bile acids (BAs), lipid metabolites, fatty acids, amino acids and phosphatidic acid (PAs), phosphatidylglycerol (PGs), glycerophospholipids (PI), phosphatidylcholines (PCs) and tripeptides. These results suggest the developed approach can be used to identify biomarkers associated with specific feeding diets and possible metabolic disorders related to diet.

SUBMITTER: Sun J

PROVIDER: S-EPMC4255139 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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A high fat, high cholesterol diet leads to changes in metabolite patterns in pigs--a metabolomic study.

Sun Jianghao J Monagas Maria M Jang Saebyeol S Molokin Aleksey A Harnly James M JM Urban Joseph F JF Solano-Aguilar Gloria G Chen Pei P

Food chemistry 20141007

Non-targeted metabolite profiling can identify biological markers of dietary exposure that lead to a better understanding of interactions between diet and health. In this study, pigs were used as an animal model to discover changes in metabolic profiles between regular basal and high fat/high cholesterol diets. Extracts of plasma, fecal and urine samples from pigs fed high fat or basal regular diets for 11 weeks were analysed using ultra-high performance liquid chromatography with high-resolutio ...[more]

PMID: 25466009

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Project description:BackgroundTestosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet.MethodsSexually mature male miniature pigs (6-7 months old) were randomly divided into 3 groups as follows: intact male pigs fed an HFC diet (IM+HFC), castrated male pigs fed an HFC diet (CM+HFC), and castrated pigs with testosterone replacement fed an HFC diet (CM+HFC+T). Serum testosterone levels and lipid profiles were measured, and gene expression levels associated with hepatic cholesterol metabolism were determined. Furthermore, total hepatic cholesterol contents and the activities of enzymes mediating hepatic cholesterol metabolism were measured.ResultsSerum testosterone levels were significantly decreased in CM+HFC pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. Castration significantly increased the serum levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as hepatic lipid contents in pigs fed an HFC diet. Compared with IM+HFC and CM+HFC+T pigs, low-density lipoprotein receptor (LDLR) mRNA expression and protein levels were significantly decreased in the livers of CM+HFC pigs. In contrast, we found that compared with IM+HFC pigs, hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and serum PCSK9 protein levels were significantly increased in CM+HFC pigs. Moreover, testosterone treatment reversed the increase in PCSK9 expression in CM+HFC pigs. However, neither castration nor testosterone replacement affected the expression of the other hepatic genes that were tested.ConclusionsThis study demonstrated that castration-induced testosterone deficiency caused severe hypercholesterolemia in pigs fed an HFC diet; furthermore, these effects could be reversed by testosterone replacement therapy. Altered hepatic PCSK9 and LDLR expression, resulting in reduced LDL-cholesterol clearance, may contribute to the increased serum cholesterol levels induced by testosterone deficiency and an HFC diet. These results deepen our understanding of the underlying molecular mechanisms that mediate the effects of testosterone deficiency on cholesterol metabolism.

Project description:Fat is one of the most important nutrients which provides concentrated energy and essential fatty acids. High fat diet markedly changes the gut microbial composition in mammals, whereas little is known about the impact of fat type on gut microbiome. This study was to evaluate the effects of fat sources on intestinal microbiota of nursery pigs. Eighteen pigs (28 days of age, 8.13 ± 0.10 kg BW) were housed individually (n = 6 per treatment) and allotted to three treatments based on a randomized complete block design. Pigs were fed basal diets with three different fat sources: 6.0% soybean oil (SBO), 6.0% palm oil (PO), and 7.5% encapsulated palm oil (EPO, contains 80% palm oil) respectively. Pigs were euthanized after 28 days of ad libitum feeding, and the digesta in the distal duodenum, jejunum, ileum, cecum and colon of each pig were obtained for microbial composition analysis. Correlation analyses were also performed between microbial composition with nutrients digestibility or growth performance. The results showed that pigs fed PO had marked changes in the bacteria community composition with increasing the richness and diversity in duodenum and jejunum (P < 0.05). Increased abundances of Proteobacteria in duodenum, jejunum and cecum, and decreased abundance of Firmicutes in jejunum were observed in pigs fed PO compared to SBO and EPO. Pigs fed EPO decreased abundances of Proteobacteria in duodenum and jejunum, and increased abundance of Firmicutes compared to pigs fed PO, and was similar to pigs fed SBO. The microbial changes (genus) had significant negative correlation with the fat digestibility. These results indicate that palm oil supplementation in nursery pig diet alters the gut microbial composition, with the most significant changes observed in small intestine. Encapsulation of palm oil, which helps increase the digestibility of palm oil, have beneficial effect on the microbial disturbance caused by palm oil supplementation. Our findings provide a better understanding of how different fat types influence microbial composition in different parts of the intestinal tract and the correlation between bacteria composition and nutrients digestibility, which may provide a new perspective for the rational application of fat in diet.

Project description:Atherosclerotic plaques are characterized by an accumulation of macrophages, lipids, smooth muscle cells, and fibroblasts, and, in advanced stages, necrotic debris within the arterial walls. Dietary habits such as high fat and high cholesterol (HFHC) consumption are known risk factors for atherosclerosis. However, the key metabolic contributors to diet-induced atherosclerosis are far from established. Herein, we investigate the role of a 2-year HFHC diet challenge in the metabolic changes of development and progression of atherosclerosis. We used a non-human primate (NHP) model (baboons, n = 60) fed a HFHC diet for two years and compared metabolomic profiles in serum from animals on baseline chow with serum collected after the challenge diet using two-dimensional gas chromatography time-of-flight mass-spectrometry (2D GC-ToF-MS) for untargeted metabolomic analysis, to quantify metabolites that contribute to atherosclerotic lesion formation. Further, clinical biomarkers associated with atherosclerosis, lipoprotein measures, fat indices, and arterial plaque formation (lesions) were quantified. Using two chemical derivatization (i.e., silylation) approaches, we quantified 321 metabolites belonging to 66 different metabolic pathways, which revealed significantly different metabolic profiles of HFHC diet and chow diet fed baboon sera. We found heritability of two important metabolites, lactic acid and asparagine, in the context of diet-induced metabolic changes. In addition, abundance of cholesterol, lactic acid, and asparagine were sex-dependent. Finally, 35 metabolites correlated (R2, 0.068-0.271, P < 0.05) with total lesion burden assessed in three arteries (aortic arch, common iliac artery, and descending aorta) which could serve as potential biomarkers pending further validation. This study demonstrates the feasibility of detecting sex-specific and heritable metabolites in NHPs with diet-induced atherosclerosis using untargeted metabolomics allowing understanding of atherosclerotic disease progression in humans.

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A high fat, high cholesterol diet leads to changes in metabolite patterns in pigs--a metabolomic study.

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A high fat, high cholesterol diet leads to changes in metabolite patterns in pigs--a metabolomic study.

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