Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice
Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27183228
PubMed Central
PMC4868278
DOI
10.1371/journal.pone.0155776
PII: PONE-D-16-00588
Knihovny.cz E-zdroje
- MeSH
- aminokyseliny krev MeSH
- analýza rozptylu MeSH
- biologické markery MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- fenotyp MeSH
- glukózový toleranční test MeSH
- inzulinová rezistence MeSH
- karnitin analogy a deriváty krev MeSH
- krevní glukóza MeSH
- metabolom MeSH
- metabolomika metody MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- obezita krev diagnóza etiologie MeSH
- porucha glukózové tolerance MeSH
- prognóza MeSH
- shluková analýza MeSH
- tendenční skóre MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acylcarnitine MeSH Prohlížeč
- aminokyseliny MeSH
- biologické markery MeSH
- karnitin MeSH
- krevní glukóza MeSH
Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity.
Zobrazit více v PubMed
Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444(7121):875–80. PubMed
Pietilainen KH, Sysi-Aho M, Rissanen A, Seppanen-Laakso T, Yki-Jarvinen H, Kaprio J, et al. Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects—a monozygotic twin study. PLOS One. 2007;2(2):e218 PubMed PMC
Pietilainen KH, Naukkarinen J, Rissanen A, Saharinen J, Ellonen P, Keranen H, et al. Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. PLOS Med. 2008;5(3):e51 10.1371/journal.pmed.0050051 PubMed DOI PMC
Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9(4):311–26. 10.1016/j.cmet.2009.02.002 PubMed DOI PMC
Illig T, Gieger C, Zhai G, Romisch-Margl W, Wang-Sattler R, Prehn C, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet. 2010;42(2):137–41. 10.1038/ng.507 PubMed DOI PMC
Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muoio DM, Newgard CB. Metabolomics applied to diabetes research: moving from information to knowledge. Diabetes. 2009;58(11):2429–43. 10.2337/db09-0580 PubMed DOI PMC
Laaksonen R, Katajamaa M, Paiva H, Sysi-Aho M, Saarinen L, Junni P, et al. A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle. PLOS ONE. 2006;1:e97 PubMed PMC
Newgard CB. Interplay between Lipids and Branched-Chain Amino Acids in Development of Insulin Resistance. Cell Metab. 2012;15(5):606–14. 10.1016/j.cmet.2012.01.024 PubMed DOI PMC
Kraegen EW, Clark PW, Jenkins AB, Daley EA, Chisholm DJ, Storlien LH. Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes. 1991;40(11):1397–403. PubMed
Storlien LH, Jenkins AB, Chisholm DJ, Pascoe WS, Khouri S, Kraegen EW. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes. 1991;40(2):280–9. PubMed
Rossmeisl M, Rim JS, Koza RA, Kozak LP. Variation in type 2 diabetes—related traits in mouse strains susceptible to diet-induced obesity. Diabetes. 2003;52(8):1958–66. PubMed
Bonnard C, Durand A, Peyrol S, Chanseaume E, Chauvin MA, Morio B, et al. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J ClinInvest. 2008;118(2):789–800. PubMed PMC
Kus V, Flachs P, Kuda O, Bardova K, Janovska P, Svobodova M, et al. Unmasking Differential Effects of Rosiglitazone and Pioglitazone in the Combination Treatment with n-3 Fatty Acids in Mice Fed a High-Fat Diet. Plos One. 2011;6(11):e27126–e27. 10.1371/journal.pone.0027126 PubMed DOI PMC
Horakova O, Medrikova D, van Schothorst EM, Bunschoten A, Flachs P, Kus V, et al. Preservation of metabolic flexibility in skeletal muscle by a combined use of n-3 PUFA and rosiglitazone in dietary obese mice. Plos One. 2012;7(8):e43764 10.1371/journal.pone.0043764 PubMed DOI PMC
Burcelin R, Crivelli V, Dacosta A, Roy-Tirelli A, Thorens B. Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet. Am J Physiol EndocrinolMetab. 2002;282(4):E834–E42. PubMed
de Fourmestraux V, Neubauer H, Poussin C, Farmer P, Falquet L, Burcelin R, et al. Transcript profiling suggests that differential metabolic adaptation of mice to a high fat diet is associated with changes in liver to muscle lipid fluxes. J Biol Chem. 2004;279(49):50743–53. PubMed
Koza RA, Nikonova L, Hogan J, Rim JS, Mendoza T, Faulk C, et al. Changes in gene expression foreshadow diet-induced obesity in genetically identical mice. PLOS Genet. 2006;2(5):e81 PubMed PMC
Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983;72(3):1150–62. PubMed PMC
Frias JP, Macaraeg GB, Ofrecio J, Yu JG, Olefsky JM, Kruszynska YT. Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women. Diabetes. 2001;50(6):1344–50. P PubMed
Priego T, Sanchez J, Pico C, Palou A. Sex-differential Expression of Metabolism-related Genes in Response to a High-fat Diet. Obesity (SilverSpring). 2008;16(4):819–26. PubMed
Guerre-Millo M, Leturque A, Girard J, Lavau M. Increased insulin sensitivity and responsiveness of glucose metabolism in adipocytes from female versus male rats. J Clin Invest. 1985;76(1):109–16. PubMed PMC
Hevener A, Reichart D, Janez A, Olefsky J. Female rats do not exhibit free fatty acid-induced insulin resistance. Diabetes. 2002;51(6):1907–12. PubMed
Medrikova D, Jilkova ZM, Bardova K, Janovska P, Rossmeisl M, Kopecky J. Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control. Int J Obes (Lond). 2012;36(2):262–72. PubMed
McInnes KJ, Corbould A, Simpson ER, Jones ME. Regulation of adenosine 5',monophosphate-activated protein kinase and lipogenesis by androgens contributes to visceral obesity in an estrogen-deficient state. Endocrinology. 2006;147(12):5907–13. PubMed
Stubbins RE, Najjar K, Holcomb VB, Hong J, Nunez NP. Estrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance. Diabetes, obesity & metabolism. 2012;14(1):58–66. PubMed PMC
Ruzickova J, Rossmeisl M, Prazak T, Flachs P, Sponarova J, Vecka M, et al. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids. 2004;39 (12):1177–85. PubMed
Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed high-fat diet. Diabetologia. 2006;49(2):394–7. PubMed
Rossmeisl M, Jelenik T, Jilkova Z, Slamova K, Kus V, Hensler M, et al. Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives. Obesity. 2009;17(5):1023–31. 10.1038/oby.2008.602 PubMed DOI
Kuda O, Jelenik T, Jilkova Z, Flachs P, Rossmeisl M, Hensler M, et al. n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia. 2009;52(5):941–51. 10.1007/s00125-009-1305-z PubMed DOI
Jelenik T, Rossmeisl M, Kuda O, Jilkova ZM, Medrikova D, Kus V, et al. AMP-activated protein kinase {alpha}2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids. Diabetes. 2010;59(11):2737–46. 10.2337/db09-1716 PubMed DOI PMC
Flachs P, Ruhl R, Hensler M, Janovska P, Zouhar P, Kus V, et al. Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids. Diabetologia. 2011;54(10):2626–38. 10.1007/s00125-011-2233-2 PubMed DOI
Rossmeisl M, Jilkova ZM, Kuda O, Jelenik T, Medrikova D, Stankova B, et al. Metabolic effects of n-3 PUFA as phospholipids are superior to triglycerides in mice fed a high-fat diet: possible role of endocannabinoids. PLoS One. 2012;7(6):e38834 10.1371/journal.pone.0038834 PubMed DOI PMC
Flachs P, Rossmeisl M, Kopecky J. The Effect of n-3 Fatty Acids on Glucose Homeostasis and Insulin Sensivity. Physiol Res. 2014:93–118. PubMed
Pawlowsky-Glahn V, Egozcue JJ, Tolosana-Delgado R. Modeling and Analysis of Compositional Data: Wiley & Sons Ltd; 2015.
Team RDC. R: A language and environment for statistical computing Vienna: R Foundation for Statistical Computing; 2010.
Templ M, Hron K, Filzmoser P. robCompositions: an R-package for robust statistical analysis of compositional data Compositional Data Analysis: Theory and Applications. OXFORD: BLACKWELL SCIENCE PUBL; 2011. p. 341–55.
Pawlowsky-Glahn V, Buccianti A. Compositional Data Analysis: Theodory and Applications: Wiley & Sons Ltd; 2012. 378 p.
Wold S, Sjostroma M, Eriksson L. PLS-regression: a basic tool of chemometrics. 2001;(58):109–30.
West DB, Boozer CN, Moody DL, Atkinson RL. Dietary obesity in nine inbred mouse strains. Am J Physiol. 1992;262(6 Pt 2):R1025–R32. PubMed
Herrera E, Lopez-Soldado I, Limones M, Amusquivar E, Ramos MP. Experimental models for studying perinatal lipid metabolism. Long-term effects of perinatal undernutrition. Adv Exp Med Biol. 2005;569:95–108. PubMed
Jimenez-Chillaron JC, Hernandez-Valencia M, Lightner A, Faucette RR, Reamer C, Przybyla R, et al. Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight. Diabetologia. 2006;49(8):1974–84. PubMed
Delahaye F, Breton C, Risold PY, Enache M, Dutriez-Casteloot I, Laborie C, et al. Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups. Endocrinology. 2008;149(2):470–5. PubMed
Collins S, Daniel KW, Petro AE, Surwit RS. Strain-specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice. Endocrinology. 1997;138:405–13. PubMed
Kleemann R, van Erk M, Verschuren L, van den Hoek AM, Koek M, Wielinga PY, et al. Time-resolved and tissue-specific systems analysis of the pathogenesis of insulin resistance. PLOS ONE. 2010;5(1):e8817 10.1371/journal.pone.0008817 PubMed DOI PMC
Geer EB, Shen W. Gender differences in insulin resistance, body composition, and energy balance. GendMed. 2009;6 Suppl 1:60–75. PubMed PMC
Wong CC, Dohler KD, Atkinson MJ, Geerlings H, Hesch RD, von zur Muhlen A. Circannual variations in serum concentrations of pituitary, thyroid, parathyroid, gonadal and adrenal hormones in male laboratory rats. The Journal of endocrinology. 1983;97(2):179–85. PubMed
Brainard GC, Petterborg LJ, Richardson BA, Reiter RJ. Pineal melatonin in syrian hamsters: circadian and seasonal rhythms in animals maintained under laboratory and natural conditions. Neuroendocrinology. 1982;35(5):342–8. PubMed
Rinaldo P, Cowan TM, Matern D. Acylcarnitine profile analysis. Genet Med. 2008;10(2):151–6. 10.1097/GIM.0b013e3181614289 PubMed DOI
Adams SH, Hoppel CL, Lok KH, Zhao L, Wong SW, Minkler PE, et al. Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J Nutr. 2009;139(6):1073–81. 10.3945/jn.108.103754 PubMed DOI PMC
Friedrich N. Metabolomics in diabetes research. J Endocrinol. 2012;215(1):29–42. 10.1530/JOE-12-0120 PubMed DOI
Mai M, Tonjes A, Kovacs P, Stumvoll M, Fiedler GM, Leichtle AB. Serum levels of acylcarnitines are altered in prediabetic conditions. PLOS One. 2013;8(12):e82459 10.1371/journal.pone.0082459 PubMed DOI PMC
Ramos-Roman MA, Sweetman L, Valdez MJ, Parks EJ. Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity. Metabolism. 2012;61(2):202–12. 10.1016/j.metabol.2011.06.008 PubMed DOI PMC
Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG, et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring). 2010;18(9):1695–700. PubMed PMC
Soeters MR, Sauerwein HP, Duran M, Wanders RJ, Ackermans MT, Fliers E, et al. Muscle acylcarnitines during short-term fasting in lean healthy men. Clin Sci (Lond). 2009;116(7):585–92. PubMed
Schooneman MG, Achterkamp N, Argmann CA, Soeters MR, Houten SM. Plasma acylcarnitines inadequately reflect tissue acylcarnitine metabolism. Biochim Biophys Acta. 2014; 1841(7):987–94. 10.1016/j.bbalip.2014.04.001 PubMed DOI
Schooneman MG, Ten Have GA, van Vlies N, Houten SM, Deutz NE, Soeters MR. Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism. Am J Physiol Endocrinol Metab. 2015;309(3):E256–64. 10.1152/ajpendo.00503.2014 PubMed DOI
Ringseis R, Wege N, Wen G, Rauer C, Hirche F, Kluge H, et al. Carnitine synthesis and uptake into cells are stimulated by fasting in pigs as a model of nonproliferating species. J Nutr Biochem. 2009;20(11):840–7. 10.1016/j.jnutbio.2008.07.012 PubMed DOI
Kien CL, Everingham KI, R DS, Fukagawa NK, Muoio DM. Short-term effects of dietary fatty acids on muscle lipid composition and serum acylcarnitine profile in human subjects. Obesity (Silver Spring). 2011;19(2):305–11. PubMed PMC
Shearer J, Duggan G, Weljie A, Hittel DS, Wasserman DH, Vogel HJ. Metabolomic profiling of dietary-induced insulin resistance in the high fat-fed C57BL/6J mouse. Diabetes, obesity & metabolism. 2008;10(10):950–8. PubMed PMC
Rizzo C, Boenzi S, Wanders RJ, Duran M, Caruso U, Dionisi-Vici C. Characteristic acylcarnitine profiles in inherited defects of peroxisome biogenesis: a novel tool for screening diagnosis using tandem mass spectrometry. Pediatr Res. 2003;53(6):1013–8. PubMed
Batch BC, Shah SH, Newgard CB, Turer CB, Haynes C, Bain JR, et al. Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness. Metabolism. 2013;62(7):961–9. 10.1016/j.metabol.2013.01.007 PubMed DOI PMC
Martin FP, Montoliu I, Collino S, Scherer M, Guy P, Tavazzi I, et al. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected]. PLOS One. 2013;8(9):e73445 10.1371/journal.pone.0073445 PubMed DOI PMC
Yamakado M, Tanaka T, Nagao K, Ishizaka Y, Mitushima T, Tani M, et al. Plasma amino acid profile is associated with visceral fat accumulation in obese Japanese subjects. Clin Obes. 2012;2(1–2):29–40. 10.1111/j.1758-8111.2012.00039.x PubMed DOI
Sailer M, Dahlhoff C, Giesbertz P, Eidens MK, de Wit N, Rubio-Aliaga I, et al. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome. PLoS One. 2013;8(5):e63950 10.1371/journal.pone.0063950 PubMed DOI PMC
Krumsiek J, Mittelstrass K, Do KT, Stuckler F, Ried J, Adamski J, et al. Gender-specific pathway differences in the human serum metabolome. Metabolomics. 2015;11(6):1815–33. PubMed PMC