PubMed

Related Articles Associations between Dietary Fiber, the Fecal Microbiota and Estrogen Metabolism in Postmenopausal Women with Breast Cancer. Nutr Cancer. 2020 Jun 26;:1-10 Authors: Zengul AG, Demark-Wahnefried W, Barnes S, Morrow CD, Bertrand B, Berryhill TF, Frugé AD Abstract Breast cancer is a hormonally-driven cancer, and various dietary factors are associated with estrogen metabolism, including dietary fiber. Several studies report associations between dietary fiber and breast cancer; however, research on whether fiber influences circulating estrogens through the gut microbiota is rare. The objective of this cross-sectional study among 29 newly-diagnosed (stage 0-II), post-menopausal breast cancer patients is to examine associations between dietary fiber and the gut microbiota that are linked with β-glucuronidase activity, and purportedly increase circulating estrogens. Spearman's and partial correlations controlling for body mass index and age were performed using dietary recall data, Illumina MiSeq generated microbiota relative abundance, and HPLC-mass spectrometry-derived estradiol and estrone levels.Major findings are: (1) total dietary fiber is inversely associated with Clostridium hathewayi (r= -0.419; p = 0.024); (2) soluble fiber is inversely associated with Clostridium (r=-0.11; p = 0.02); (3) insoluble fiber is positively associated with Bacteroides uniformis sp. (r = 0.382; p = 0.041); and (4) serum estradiol and estrone levels are not correlated with species/genera or dietary fiber, though there is a trend toward an inverse association between soluble fiber and estradiol levels (r= -0.30; p = 0.12). More studies are needed to understand the complex interaction between dietary fiber, intestinal microbiota, and hormonal levels in older females. PMID: 32590914 [PubMed - as supplied by publisher]

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/26PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/25PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/24PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Different Malabsorptive Obesity Surgery Interventions Result in Distinct Postprandial Amino Acid Metabolomic Signatures. Obes Surg. 2020 Jun 20;: Authors: Pereira SS, Jarak I, Carvalho RA, Oliveira PF, Alves MG, Guimarães M, Almeida R, Pereira AM, Wewer Albrechtsen NJ, Holst JJ, Nora M, Monteiro MP Abstract PURPOSE: Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective weight loss surgical procedure. Yet, BPD-DS is technically difficult to perform and carries a higher risk of nutrient deficiencies as compared with other surgical interventions. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modified BPD-DS procedure conceived with the aim of decreasing the technical complexity, while retaining the weight loss efficiency. Whether the two surgical procedures diverge in nutrient absorption rates and malnutrition risk is still matter of debate. Our aim was to determine if postprandial nutrient absorption rates are different in patients subjected to BPD-DS or SADI-S for weight loss. MATERIALS AND METHODS: Plasma amino acid metabolomic profiling during mixed-meal tolerance test (MMTT) was performed in subjects (N = 18) submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.6 ± 0.1 years earlier. RESULTS: Patients submitted to SADI-S or BPD-DS presented distinct postprandial metabolomic profiles. Postprandial excursions of total and essential amino acids-leucine, isoleucine, and valine-were higher after SADI-S as compared with BPD-DS. CONCLUSION: Our study demonstrates that a simplified malabsorptive bariatric surgery procedure SADI-S results in greater essential branched-chain amino acid absorption when compared with the classical BPD-DS intervention. These findings suggest that SADI-S can potentially lower lifetime risk of postoperative protein malnutrition, as well as have a positive impact on systemic metabolism and glucose homeostasis. PMID: 32564307 [PubMed - as supplied by publisher]

Related Articles GlycA, a novel marker for low grade inflammation, reflects gut microbiome diversity and is more accurate than high sensitive CRP in reflecting metabolomic profile. Metabolomics. 2020 Jun 20;16(7):76 Authors: Mokkala K, Houttu N, Koivuniemi E, Sørensen N, Nielsen HB, Laitinen K Abstract INTRODUCTION: Gut microbiota is, along with adipose tissue, recognized as a source for many metabolic and inflammatory disturbances that may contribute to the individual's state of health. OBJECTIVES: We investigated in cross-sectional setting the feasibility of utilizing GlycA, a novel low grade inflammatory marker, and traditional low grade inflammatory marker, high sensitivity CRP (hsCRP), in reflecting serum metabolomics status and gut microbiome diversity. METHODS: Fasting serum samples of overweight/obese pregnant women (n = 335, gestational weeks: mean 13.8) were analysed for hsCRP by immunoassay, GlycA and metabolomics status by NMR metabolomics and faecal samples for gut microbiome diversity by metagenomics. The benefits of GlycA as a metabolic marker were investigated against hsCRP. RESULTS: The GlycA concentration correlated with more of the metabolomics markers (144 out of 157), than hsCRP (55 out of 157) (FDR < 0.05). The results remained essentially the same when potential confounding factors known to associate with GlycA and hsCRP levels were taken into account (P < 0.05). This was attributable to the detected correlations between GlycA and the constituents and concentrations of several sized VLDL-particles and branched chain amino acids, which were statistically non-significant with regard to hsCRP. GlycA, but not hsCRP, correlated inversely with gut microbiome diversity. CONCLUSION: GlycA is a superior marker than hsCRP in assessing the metabolomic profile and gut microbiome diversity. It is proposed that GlycA may act as a novel marker that reflects both the gut microbiome and adipose tissue originated metabolic aberrations; this proposal will need to be verified with regard to clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01922791, August 14, 2013. PMID: 32564244 [PubMed - as supplied by publisher]

Related Articles Sphingomyelin and progression of renal and coronary heart disease in individuals with type 1 diabetes. Diabetologia. 2020 Jun 20;: Authors: Pongrac Barlovic D, Harjutsalo V, Sandholm N, Forsblom C, Groop PH, FinnDiane Study Group Abstract AIMS/HYPOTHESIS: Lipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes. METHODS: Individuals (n = 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria. RESULTS: During a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median [IQR] for eGFR change: <-4.4 [-6.8, -3.1] ml min-1 [1.73 m-2] year-1), even after adjustment for classical lipid variables such as HDL-cholesterol and triacylglycerols (OR [95% CI]: 1.36 [1.15, 1.61], p < 0.001). Similarly, sphingomyelin increased the risk of progression to ESRD (HR [95% CI]: 1.53 [1.19, 1.97], p = 0.001). Moreover, sphingomyelin increased the risk of CHD (HR [95% CI]: 1.24 [1.01, 1.52], p = 0.038). However, sphingomyelin did not perform better than albuminuria in the prediction of eGFR decline. CONCLUSIONS/INTERPRETATION: This study demonstrates for the first time in a prospective setting that sphingomyelin is associated with the fastest eGFR decline and progression to ESRD in type 1 diabetes. In addition, sphingomyelin is a risk factor for CHD. These data suggest that high sphingomyelin level, independently of classical lipid risk factors, may contribute not only to the initiation and progression of kidney disease but also to CHD. Graphical abstract. PMID: 32564139 [PubMed - as supplied by publisher]

Related Articles The impact of metabolites derived from the gut microbiota on immune regulation and diseases. Int Immunol. 2020 Jun 20;: Authors: Ohno H Abstract Gut microbiota strongly impacts the physiology and pathology in the host. To understand the complex interactions between host and gut microbiota, an "integrated omics" approach has been employed, where exhaustive analyses for the different layers of cellular functions, such as epigenomics, transcriptomics and metabolomics, in addition to metagenomics, are combined. With this approach, the mechanisms whereby short-chain fatty acids (SCFAs) regulate host defense and the immune system have been elucidated. In a gnotobiotic mouse model of enterohemorrhagic Escherichia coli infection, Bifidobacterium-derived acetate can protect from infection-mediated death by changing the gene expression profile of colonic epithelial cells. It has also been shown that gut microbiota-derived butyrate enhances colonic regulatory T-cell differentiation through its epigenetic modulatory ability via histone deacetylase inhibition. SCFAs are involved in many other immunomodulatory effects as well as host pathophysiological conditions. Dysbiosis in the gut has been implicated in the pathogenesis of many diseases. Although the causal relationship of gut microbial dysbiosis and/or metabolites with pathogenesis is mostly unknown, mechanistic insights have been elucidated in some cases. Metabolism in the gut microbiota and host liver produces trimethylamine N-oxide, which is known to aggravate atherosclerosis, and a secondary bile acid deoxycholate, which reportedly induces nonalcoholic steatohepatitis-related hepatocellular carcinoma (HCC). It has been reported that secondary bile acids could also induce the differentiation of peripherally derived regulatory T cells (pTregs) in the gut. Further studies on the interactions between the host and gut microbiota could lead to the development of new therapeutic strategies as well as in preventive medicine. PMID: 32564086 [PubMed - as supplied by publisher]

Related Articles Serum zonulin measured by enzyme-linked immunosorbent assay may not be a reliable marker of small intestinal permeability in healthy adults. Nutr Res. 2020 May 19;78:82-92 Authors: Tatucu-Babet OA, Forsyth A, Owen E, Navarro-Perez D, Radcliffe J, Benheim D, Mendis H, Jois M, Itsiopoulos C, Tierney AC Abstract The association between intestinal permeability (IP) and body composition remains unclear. The gold standard differential sugar-absorption test is arduous to complete, with zonulin being increasingly used as an independent biomarker of IP. This pilot study aimed to explore the association between small IP, zonulin concentrations, and body composition in healthy adults. The urinary lactulose-rhamnose ratio was used to measure small IP. Serum zonulin, lipopolysaccharide (LPS) and high-sensitivity C-reactive protein (hs-CRP) were analyzed in serum. Body composition was measured using dual-energy X-ray absorptiometry and anthropometric measurements were collected. In total, 34 participants were included (12 males, median age 28 years, body mass index 24 kg/m2, waist circumference 77cm). No correlation was observed between the lactulose-rhamnose ratio and zonulin (r = -.016, P = .929). The lactulose-rhamnose ratio displayed a strong positive correlation with LPS (n 20, r = .536, P = .018) but did not correlate with body composition measures. Conversely, zonulin displayed a moderate positive correlation with waist circumference (r = .437, P = .042) in female participants and hs-CRP (r = .485, P = .004) in all participants. These findings raise important considerations for the measurement of small IP, warranting exploration in larger powered studies that address the limitations of the present study. PMID: 32563954 [PubMed - as supplied by publisher]

Related Articles What are the effects of PFAS exposure at environmentally relevant concentrations? Chemosphere. 2020 Jun 12;258:127340 Authors: Sinclair GM, Long SM, Jones OAH Abstract The group of synthetic chemicals known as poly and per-fluoroalkyl substances (PFAS) are currently of high concern to environmental regulators and the public due to their widespread occurrence, resistance to degradation and reported toxicity. However, little data exists on the effects of exposure to PFAS at environmentally relevant concentrations and this hampers the effective management of these compounds. This paper reviews current research on the occurrence and ecotoxicology of PFAS at environmentally relevant doses to assess their potential biological impacts. Hazard Quotient (HQ) analysis was undertaken as part of this assessment. Most PFAS detected in the environment were found to have a HQ risk value of <1 meaning their reported concentrations are below their predicted no effect concentration. This indicates many reported toxic effects of PFAS are, theoretically, unlikely to occur outside the laboratory. However, lack of information on new PFAS as well as their precursors and degradation products, coupled with lack of knowledge of their mixture toxicity means our understanding of the risks of PFAS is incomplete, especially in regard to sub-lethal and/or chronic effects. It is proposed that the development of molecular markers for PFAS exposure are needed to aid in the development of environmental PFAS regulations that are effective in fully protecting the environment. PMID: 32563917 [PubMed - as supplied by publisher]

Related Articles Global and local diet popularity rankings, their secular trends, and seasonal variation in Google Trends data. Nutrition. 2020 Feb 12;79-80:110759 Authors: Kamiński M, Skonieczna-Żydecka K, Nowak JK, Stachowska E Abstract OBJECTIVES: The Internet has become the main source of health-related information including nutrition. The aim of this study was to rank the most popular diets among Google users globally and regionally in addition to secular and seasonal trends in the years 2004 to 2019. METHODS: We used Google Trends (GT) to identify and analyze course over time and regional interest of 47 topics related to diets. We analyzed secular trends using the Seasonal Mann-Kendall test and seasonal variation using time-series decomposition. The topic "Mediterranean diet" (MedD) was used as a benchmark. We calculated the interest of all topics in proportion to the relative search volume (RSV) of MedD. RESULTS: Globally, Google users were particularly interested in veganism (19.54 times higher than MedD), vegetarianism (15.09 times higher than MedD), and gluten-free diet (11.11 times higher than MedD). Veganism was the most frequently searched diet type in 23 countries followed by vegetarianism (14), ketogenic diet (7), and low-carbohydrate diet (7). Whereas an increase of RSV over time was observed for 23 diets, a decrease was noted for 20. The most dynamic increase was found for FODMAP (6.12 RSV/year), gluten-free diet (5.95 RSV/year), and raw veganism (5.72 RSV/year). Sharp declines concerned negative-calorie food (-4.34 RSV/year), macrobiotic diet (-3.89 RSV/year), and cabbage soup diet (-3.50 RSV/year). The interest in most diets falls in December but peaks in January. CONCLUSION: Veganism, vegetarianism, and gluten-free diet attract the largest public interest globally. Both secular trends and seasonal variation shape the ever-changing landscape of diet popularity. GT holds promise as a valuable tool in local and international nutrition research. PMID: 32563767 [PubMed - as supplied by publisher]

Related Articles Amino acid metabolism, lipid metabolism, and oxidative stress are associated with post-stroke depression: a metabonomics study. BMC Neurol. 2020 Jun 20;20(1):250 Authors: Wang M, Gui X, Wu L, Tian S, Wang H, Xie L, Wu W Abstract BACKGROUND: Post-stroke depression (PSD) is a mood disorder characterized by depression and anhedonia caused by stroke. Metabolomics identified metabolites associated with PSD, but previous studies are based on gas chromatography (GC)/mass spectrometry (MS). This study aimed to perform a liquid chromatography (LC)-MS-based metabolomics study of the plasma metabolite profiles between patients with PSD and controls. METHODS: This was a prospective study of patients with stroke enrolled between July and December 2017 at the Second Affiliated Hospital of Nanchang University. Patients were grouped as Hamilton Depression Rating Scale > 7 (PSD) or < 7 (controls). Metabonomics profiling of plasma sampled was conducted by LC-MS. By combining multivariable and univariable statistical analyses, significant differential metabolites between the two groups were screened. The threshold for significant differences was VIP ≥1 and P < 0.05. Log2FC is the logarithm of the mean ratio between the two groups. RESULTS: There were no significant difference with respect to age, NIHSS score, and MMSE between the two groups (all P > 0.05). There were six differential metabolites between the PSD and stroke groups, of which three metabolites were increased and three were decreased. Compared with the control group, p-chlorophenylalanine (Log2FC = 1.37, P = 0.03), phenylacetyl glutamine (Log2FC = 0.21, P = 0.048), and DHA (Log2FC = 0.77, P = 0.01) levels were higher in the PSD group, while betaine (trimethylglycine) (Log2FC = - 0.79, P = 0.04), palmitic acid (Log2FC = - 0.51, P = 0.001), and MHPG-SO4 (Log2FC = - 2.37, P = 0.045) were decreased. CONCLUSION: Plasma metabolomics showed that amino acid metabolism (phenylacetyl glutamine, p-chlorophenylalanine, trimethylglycine), lipid metabolism (DHA, palmitic acid, trimethylglycine), and oxidative stress (DHA, palmitic acid, trimethylglycine) were associated with PSD. These results could help to reveal the pathophysiological mechanism of PSD and eventually identify treatment targets. PMID: 32563250 [PubMed - as supplied by publisher]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles PHGDH supports liver ceramide synthesis and sustains lipid homeostasis. Cancer Metab. 2020;8:6 Authors: Kang YP, Falzone A, Liu M, González-Sánchez P, Choi BH, Coloff JL, Saller JJ, Karreth FA, DeNicola GM Abstract Background: d-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown. Methods: To study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter. With this model, PHGDH depletion can be globally induced in adult animals, while sparing the brain due to poor doxycycline delivery. Results: We found that PHGDH depletion is well tolerated, and no overt phenotypes were observed in multiple highly proliferative cell compartments. Further, despite detectable knockdown and impaired serine synthesis, liver and pancreatic functions were normal. Interestingly, diminished PHGDH expression reduced liver serine and ceramide levels without increasing the levels of deoxysphingolipids. Further, liver triacylglycerol profiles were altered, with an accumulation of longer chain, polyunsaturated tails upon PHGDH knockdown. Conclusions: These results suggest that dietary serine is adequate to support the function of healthy, adult murine tissues, but PHGDH-derived serine supports liver ceramide synthesis and sustains general lipid homeostasis. PMID: 32549981 [PubMed]

Related Articles Population-based case-control study revealed metabolomic biomarkers of suboptimal health status in Chinese population-potential utility for innovative approach by predictive, preventive, and personalized medicine. EPMA J. 2020 Jun;11(2):147-160 Authors: Wang H, Tian Q, Zhang J, Liu H, Zhang X, Cao W, Zhang J, Anto EO, Li X, Wang X, Liu D, Zheng Y, Guo Z, Wu L, Song M, Wang Y, Wang W Abstract Background: Suboptimal health status (SHS) is a subclinical stage of chronic diseases, and the identification of SHS provides an opportunity for the predictive, preventive, and personalized medicine (PPPM) of chronic diseases. Previous studies have reported the associations between metabolic signatures and early signs of chronic diseases. Methods: This study aimed to detect the metabolic biomarkers for the identification of SHS in a case-control study. SHS questionnaire-25 (SHSQ-25) was used in a population-based health survey to measure the SHS levels of participants. The liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was conducted on plasma samples collected from 50 SHS participants and 50 age- and sex-matched healthy controls. Results: After adjusting for the confounders, 24 significantly differential metabolites, such as sphingomyelin, sphingosine, sphinganine, progesterone, pregnanolone, and bilirubin, were identified as the candidate biomarkers for SHS. Pathway analysis revealed that sphingolipid metabolism, taurine metabolism, and steroid hormone biosynthesis are the disturbed metabolic pathways related to SHS. A combination of four metabolic biomarkers (sphingosine, pregnanolone, taurolithocholate sulfate, cervonyl carnitine) can distinguish SHS individuals from the controls with a sensitivity of 94.0%, a specificity of 90.0%, and an area under the receiver operating characteristic curve of 0.977. Conclusion: Plasma metabolites are valuable biomarkers for SHS identification, and meanwhile, SHSQ-25 can be used as an alternative health screening tool in the population-based health survey. SHS-related metabolic disturbances could be detected at the early onset of SHS, and SHS-related metabolites could create a window opportunity for PPPM of chronic diseases. PMID: 32549914 [PubMed]

Related Articles Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective. Metabolites. 2020 Jun 15;10(6): Authors: Fan TW, Higashi RM, Chernayavskaya Y, Lane AN Abstract The tumor microenvironment (TME) comprises complex interactions of multiple cell types that determines cell behavior and metabolism such as nutrient competition and immune suppression. We discuss the various types of heterogeneity that exist in solid tumors, and the complications this invokes for studies of TME. As human subjects and in vivo model systems are complex and difficult to manipulate, simpler 3D model systems that are compatible with flexible experimental control are necessary for studying metabolic regulation in TME. Stable Isotope Resolved Metabolomics (SIRM) is a valuable tool for tracing metabolic networks in complex systems, but at present does not directly address heterogeneous metabolism at the individual cell level. We compare the advantages and disadvantages of different model systems for SIRM experiments, with a focus on lung cancer cells, their interactions with macrophages and T cells, and their response to modulators in the immune microenvironment. We describe the experimental set up, illustrate results from 3D cultures and co-cultures of lung cancer cells with human macrophages, and outline strategies to address the heterogeneous TME. PMID: 32549391 [PubMed]

Related Articles A Tale of Two Biomarkers: Untargeted 1H NMR Metabolomic Fingerprinting of BHBA and NEFA in Early Lactation Dairy Cows. Metabolites. 2020 Jun 15;10(6): Authors: Luke TDW, Pryce JE, Wales WJ, Rochfort SJ Abstract Disorders of energy metabolism, which can result from a failure to adapt to the period of negative energy balance immediately after calving, have significant negative effects on the health, welfare and profitability of dairy cows. The most common biomarkers of energy balance in dairy cows are β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA). While elevated concentrations of these biomarkers are associated with similar negative health and production outcomes, the phenotypic and genetic correlations between them are weak. In this study, we used an untargeted 1H NMR metabolomics approach to investigate the serum metabolomic fingerprints of BHBA and NEFA. Serum samples were collected from 298 cows in early lactation (calibration dataset N = 248, validation N = 50). Metabolomic fingerprinting was done by regressing 1H NMR spectra against BHBA and NEFA concentrations (determined using colorimetric assays) using orthogonal partial least squares regression. Prediction accuracies were high for BHBA models, and moderately high for NEFA models (R2 of external validation of 0.88 and 0.75, respectively). We identified 16 metabolites that were significantly (variable importance of projection score > 1) correlated with the concentration of one or both biomarkers. These metabolites were primarily intermediates of energy, phospholipid, and/or methyl donor metabolism. Of the significant metabolites identified; (1) two (acetate and creatine) were positively correlated with BHBA but negatively correlated with NEFA, (2) nine had similar associations with both BHBA and NEFA, (3) two were correlated with only BHBA concentration, and (4) three were only correlated with NEFA concentration. Overall, our results suggest that BHBA and NEFA are indicative of similar metabolic states in clinically healthy animals, but that several significant metabolic differences exist that help to explain the weak correlations between them. We also identified several metabolites that may be useful intermediate phenotypes in genomic selection for improved metabolic health. PMID: 32549362 [PubMed]