Comparative Nontargeted Profiling of Metabolic Changes in Tissues and Biofluids in High-Fat Diet-Fed Ossabaw Pig

Abstract

Typical clinical biomarker analyses on urine and plasma samples from human dietary interventions do not provide adequate information about diet-induced metabolic changes taking place in tissues. The aim of this study was to show how a large-scale nontargeted metabolomic approach can be used to reveal metabolite groups for generating new hypotheses of obesity-related metabolic disturbances produced in an animal model. A large spectrum of metabolites in the semipolar region, including small water-soluble molecules like betaine and dihydroxyindole, and a wide range of bile acids as well as various lipid species were detected. The high-fat diet influenced metabolic homeostasis of Ossabaw pigs, especially the lipid metabolome, throughout all the analyzed sample types, including plasma, urine, bile, liver, pancreas, brain cortex, intestinal jejunum and proximal colon. However, even dramatic metabolic changes in tissues were not necessarily observed in plasma and urine. Metabolite profiling involving multiple sample types was shown to be a feasible method for the examination of a wide spectrum of metabolic species extending from small water-soluble metabolites to an array of bile acids and lipids, thus pointing to the pathways of metabolism affected by the dietary treatment.

High‐Fat Diet, Betaine, and Polydextrose Induce Changes in Adipose Tissue Inflammation and Metabolism in C57BL/6J Mice

“…In various animal and human studies, metabolite profiling has revealed significant alterations in lipid profiles due to HF diet, obesity, and obesity‐related disorders . In Ossabaw pigs, the levels of various lipid species change significantly in plasma due to an HF diet . In our study, the HF diet decreased the levels of nearly all identified lipids in adipose tissue, but the effect of dietary supplements on circulating lipids was not measured.…”

“…The HF diet lowered the levels of butyrobetaine and unknown BET species in SAT but did not alter (glycine)‐BET content. Other studies have also reported changes in BET synthesis in fat‐induced animals …”

Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach

“…BET supplementation has consistently led to accumulation of BET in liver in various animal models including broiler chicks , pigs , and mouse , and in muscle of pigs . Metabolic disturbances will lead to reduced BET levels in liver, as seen in obese rat and mice models , and in pancreas and different parts of intestinal tissue as recently seen in Ossabaw pig . Also, low circulating BET levels have been associated with lipid disorders and metabolic syndrome in humans, and BET insufficiency has been suggested to be a common feature of the metabolic syndrome .…”

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

“…Many of these studies investigated the particular role of metabolites in inflammatory bowel diseases by using primarily NMR studies (Lin et al, 2011). Non-targeted metabolomics approaches in gut microbial sample matrices and liver, analysing changes occurring in metabolic diseases like obesity, are rarely given, but many studies addressed obesity-related metabolome characterization (Dumas et al, 2006;Williams et al, 2006;Fearnside et al, 2008;Li et al, 2008Li et al, , 2010aShearer et al, 2008;Newgard et al, 2009;Waldram et al, 2009;Kim et al, 2009Kim et al, , 2010Kim et al, , 2011Calvani et al, 2010;Xie et al, 2010Xie et al, , 2012Zhao et al, 2010;Oberbach et al, 2011;Duggan et al, 2011a,b;Jung et al, 2012;Hanhineva et al, 2013;Schäfer et al, 2014;Seyfried et al, 2013;Won et al, 2013;Xu et al, 2013;Daniel et al, 2014;Eisinger et al, 2014). Comparing with other studies, our study provides a greater insight into different metabolite classes that were involved in obesity-related changes by reflecting both bacterial and host metabolism.…”