Investigating Potential Mechanisms of Obesity by Metabolomics

Obesity is a serious health problem with an increased risk of several common diseases including diabetes, cardiovascular disease, and cancer. Metabolomics is an emerging analytical technique for systemic determination of metabolite profiles, which is useful for understanding the biochemical changes in obesity or related diseases both in individual organs and at the organism level. Increasingly, this technology has been applied to the study of obesity, complementing transcriptomics and/or proteomics analyses. Indeed, the alterations of metabolites in biofluids/tissues are direct indicators of variations in physiology or pathology. In this paper, we will examine the obesity-related alterations in significant metabolites that have been identified by metabolomics as well as their metabolic pathway associations. Issues concerning the screening of biologically significant metabolites related to obesity will also be discussed.

[1]  H. Vogel,et al.  Differentiating short‐ and long‐term effects of diet in the obese mouse using 1H‐nuclear magnetic resonance metabolomics , 2011, Diabetes, obesity & metabolism.

[2]  Peter Kovacs,et al.  Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes. , 2011, Journal of proteome research.

[3]  J. Calviño,et al.  Metabolic acidosis-induced insulin resistance and cardiovascular risk. , 2011, Metabolic syndrome and related disorders.

[4]  Wolfram Gronwald,et al.  Discrimination of steatosis and NASH in mice using nuclear magnetic resonance spectroscopy , 2011, Metabolomics.

[5]  M. Shlipak,et al.  Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. , 2011, JAMA.

[6]  Hannelore Daniel,et al.  Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention. , 2011, Physiological genomics.

[7]  V. Mootha,et al.  Metabolite profiles and the risk of developing diabetes , 2011, Nature Medicine.

[8]  Jie Tian,et al.  Obesity in China: what are the causes? , 2011, Current pharmaceutical design.

[9]  Brian J. Bennett,et al.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease , 2011, Nature.

[10]  Jae Ho Park,et al.  Metabolomic analysis of livers and serum from high-fat diet induced obese mice. , 2011, Journal of proteome research.

[11]  C. Sensen,et al.  Metabolomic response to exercise training in lean and diet-induced obese mice. , 2011, Journal of applied physiology.

[12]  Ratnesh K Singh,et al.  The impact of choline availability on muscle lipid metabolism. , 2011, Food & function.

[13]  Liang Zhao,et al.  A Metabonomic Comparison of Urinary Changes in Zucker and GK Rats , 2010, Journal of biomedicine & biotechnology.

[14]  J. H. Lee,et al.  Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). , 2010, Journal of proteome research.

[15]  Terry K. Smith,et al.  The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine , 2010, IUBMB life.

[16]  Susan C Connor,et al.  Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes. , 2010, Molecular bioSystems.

[17]  G. Mingrone,et al.  Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype , 2010, International Journal of Obesity.

[18]  Kazuki Saito,et al.  Integrated omics approaches in plant systems biology. , 2009, Current opinion in chemical biology.

[19]  Seung-Ok Yang,et al.  1H-nuclear magnetic resonance spectroscopy-based metabolic assessment in a rat model of obesity induced by a high-fat diet , 2009, Analytical and bioanalytical chemistry.

[20]  John C Lindon,et al.  ¹H NMR-based metabonomics for investigating diabetes. , 2009, Future medicinal chemistry.

[21]  Jesús Brezmes,et al.  Metabolic phenotyping of genetically modified mice: An NMR metabonomic approach. , 2009, Biochimie.

[22]  B. Nugraha,et al.  Metabolomics Study With Gas Chromatography–Mass Spectrometry for Predicting Valproic Acid–induced Hepatotoxicity and Discovery of Novel Biomarkers in Rat Urine , 2009, International journal of toxicology.

[23]  H. Yoo,et al.  Characterization of Plasma Carnitine Level in Obese Adolescent Korean Women , 2009 .

[24]  M. Rantalainen,et al.  Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. , 2009, Journal of proteome research.

[25]  Svati H Shah,et al.  A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. , 2009, Cell metabolism.

[26]  S. Eckhardt,et al.  Clinical Applications of Metabolomics in Oncology: A Review , 2009, Clinical Cancer Research.

[27]  J. Lindon,et al.  Systems biology: Metabonomics , 2008, Nature.

[28]  Kai Song,et al.  Transcriptomic and metabonomic profiling of obesity-prone and obesity-resistant rats under high fat diet. , 2008, Journal of proteome research.

[29]  H. Vogel,et al.  Metabolomic profiling of dietary‐induced insulin resistance in the high fat–fed C57BL/6J mouse , 2008, Diabetes, obesity & metabolism.

[30]  J. Speakman,et al.  The contribution of animal models to the study of obesity , 2008, Laboratory animals.

[31]  D. Craik,et al.  Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study , 2008, PloS one.

[32]  J. Lindon,et al.  Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. , 2008, Annual review of analytical chemistry.

[33]  R. Green,et al.  Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet , 2008 .

[34]  D. Gauguier,et al.  Phylometabonomic Patterns of Adaptation to High Fat Diet Feeding in Inbred Mice , 2008, PloS one.

[35]  J. Griffin,et al.  Applications of metabolomics to understanding obesity in mouse and man. , 2007, Biomarkers in medicine.

[36]  Pengxiang She,et al.  Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. , 2007, American journal of physiology. Endocrinology and metabolism.

[37]  S. McCall,et al.  Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis , 2007, Hepatology.

[38]  M. Watford Lowered concentrations of branched-chain amino acids result in impaired growth and neurological problems: insights from a branched-chain alpha-keto acid dehydrogenase complex kinase-deficient mouse model. , 2007, Nutrition reviews.

[39]  J. Soh,et al.  L-Carnitine Reduces Obesity Caused by High-Fat Diet in C57BL/6J Mice , 2007 .

[40]  F. Yoshizawa,et al.  Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis. , 2007, American journal of physiology. Endocrinology and metabolism.

[41]  E. Mardis,et al.  An obesity-associated gut microbiome with increased capacity for energy harvest , 2006, Nature.

[42]  C. Lynch,et al.  Leucine in food mediates some of the postprandial rise in plasma leptin concentrations. , 2006, American journal of physiology. Endocrinology and metabolism.

[43]  M. McCarthy,et al.  Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice , 2006, Proceedings of the National Academy of Sciences.

[44]  Martin Kussmann,et al.  OMICS-driven biomarker discovery in nutrition and health. , 2006, Journal of biotechnology.

[45]  Y. Kamei,et al.  Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity. , 2006, Endocrinology.

[46]  John C. Lindon,et al.  Metabonomics Techniques and Applications to Pharmaceutical Research & Development , 2006, Pharmaceutical Research.

[47]  Ryutaro Hirose,et al.  Metabolic profiling of livers and blood from obese Zucker rats. , 2006, Journal of hepatology.

[48]  M. Brändle,et al.  Increased prevalence of high Body Mass Index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma. , 2006, Swiss medical weekly.

[49]  I. Wilson,et al.  A multi-analytical platform approach to the metabonomic analysis of plasma from normal and Zucker (fa/fa) obese rats. , 2006, Molecular bioSystems.

[50]  T. Schulz,et al.  Chemical inhibition of citrate metabolism alters body fat content in mice. , 2006, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[51]  R. Teasdale,et al.  In Vivo Analysis of Growth Hormone Receptor Signaling Domains and Their Associated Transcripts , 2005, Molecular and Cellular Biology.

[52]  C. Hoppel,et al.  Carnitine: a nutritional, biosynthetic, and functional perspective. , 2004, Molecular aspects of medicine.

[53]  Robert A. Harris,et al.  Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise. , 2004, The Journal of nutrition.

[54]  S. Kagamimori,et al.  Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects , 2004, Amino Acids.

[55]  J. Wong,et al.  Long‐term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial , 2004, Alimentary pharmacology & therapeutics.

[56]  S. Amini,et al.  Effect of enteral glutamine or glycine on whole-body nitrogen kinetics in very-low-birth-weight infants. , 2004, The American journal of clinical nutrition.

[57]  J. Pankow,et al.  Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. , 2003, The American journal of clinical nutrition.

[58]  P. Durrington,et al.  Preventing cardiovascular disease in hypertension: effects of lowering blood pressure and cholesterol. , 2002, QJM : monthly journal of the Association of Physicians.

[59]  T. Lakka,et al.  Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle‐aged men , 2002, Diabetic medicine : a journal of the British Diabetic Association.

[60]  J. ArancetaBartrina [Prevalence of obesity in developed countries: current status and perspectives]. , 2002 .

[61]  T. Weinstein,et al.  Glomerular hemodynamics in severe obesity. , 2000, American journal of physiology. Renal physiology.

[62]  P. J. Randle,et al.  Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. , 1998, Diabetes/metabolism reviews.

[63]  J. Blusztajn,et al.  Choline, a Vital Amine , 1998, Science.

[64]  J. Hill,et al.  Childhood Obesity: Future Directions and Research Priorities , 1998, Pediatrics.

[65]  M. Ohrvall,et al.  The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up. , 1996, Atherosclerosis.

[66]  S. Mitchell,et al.  The exogenous origin of trimethylamine in the mouse. , 1992, Metabolism: clinical and experimental.

[67]  J. Bosch,et al.  Effect of diet on creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease. , 1991, Journal of the American Society of Nephrology : JASN.

[68]  E. Alexander,et al.  Choline, an essential nutrient for humans , 1991, Nutrition.

[69]  M. Jeevanandam,et al.  Altered plasma free amino acid levels in obese traumatized man. , 1991, Metabolism: clinical and experimental.

[70]  N. Sugino [Evaluation of renal function in chronic renal disease with special reference to creatinine]. , 1990, Nihon Jinzo Gakkai shi.

[71]  A. Golay,et al.  Effect of obesity on ambient plasma glucose, free fatty acid, insulin, growth hormone, and glucagon concentrations. , 1986, The Journal of clinical endocrinology and metabolism.

[72]  G. Marchesini,et al.  Insulin-dependent metabolism of branched-chain amino acids in obesity. , 1984, Metabolism: clinical and experimental.

[73]  D. Simpson Citrate excretion: a window on renal metabolism. , 1983, The American journal of physiology.

[74]  R. Sherwin Effect of starvation on the turnover and metabolic response to leucine. , 1978, The Journal of clinical investigation.

[75]  P. Felig,et al.  Splanchnic glucose and amino acid metabolism in obesity. , 1974, The Journal of clinical investigation.

[76]  R. Kreisberg Glucose-lactate inter-relations in man. , 1972, The New England journal of medicine.

[77]  A. Drash,et al.  Hormone and amino acid levels in altered nutritional states. , 1970, The Journal of laboratory and clinical medicine.

[78]  P. Felig,et al.  Plasma amino acid levels and insulin secretion in obesity. , 1969, The New England journal of medicine.

[79]  C. Swartz,et al.  Creatinine clearance in renal disease. A reappraisal , 1969, British medical journal.

[80]  D. Devilliers,et al.  Citrate metabolism in diabetes. I. Plasma citrate in alloxan-diabetic rats and in clinical diabetes. , 1966, Metabolism: clinical and experimental.

[81]  F. Konishi THE RELATIONSHIP OF URINARY 17-HYDROXYCORTICOSTEROIDS TO CREATININE IN OBESITY. , 1964, Metabolism: clinical and experimental.

[82]  S. Natelson,et al.  Dynamic control of calcium, phosphate, citrate, and glucose levels in blood serum. Effect of ACTH, adrenaline, noradrenaline, hydrocortisone, parathormone, insulin, and glucagon. , 1963, Clinical chemistry.

[83]  J. Walker Metabolic control of creatine biosynthesis. II. Restoration of transamidinase activity following creatine repression. , 1961, The Journal of biological chemistry.

[84]  H. Popper,et al.  Urinary excretion of choline metabolites following choline administration in normals and patients with hepatobiliary diseases. , 1951, The Journal of clinical investigation.

[85]  Y. Cha Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid. , 2008, Asia Pacific journal of clinical nutrition.

[86]  E. Pasquali,et al.  Insulin resistance and low urinary citrate excretion in calcium stone formers. , 2007, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[87]  P. A. Tataranni,et al.  Microarray gene expression profiling in obesity and insulin resistance. , 2004, Nutrition.

[88]  R. Green,et al.  The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. , 2004, Journal of hepatology.

[89]  R. Curi,et al.  Glutamine and glutamate as vital metabolites. , 2003, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[90]  J. Aranceta Bartrina [Prevalence of obesity in developed countries: current status and perspectives]. , 2002, Nutricion hospitalaria.

[91]  J. Culebras,et al.  [Evaluation of Hospital Nutrition III. Delay, subjects and citation]. , 2002, Nutricion hospitalaria.

[92]  M. Holeček,et al.  The BCAA-BCKA cycle: its relation to alanine and glutamine synthesis and protein balance. , 2001, Nutrition.

[93]  Y. Nakaya,et al.  Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. , 2000, The American journal of clinical nutrition.

[94]  H. Satoh Cardioprotective actions of taurine against intracellular and extracellular calcium-induced effects. , 1994, Advances in experimental medicine and biology.

[95]  P. Jansson,et al.  Lactate release from the subcutaneous tissue in lean and obese men. , 1994, The Journal of clinical investigation.

[96]  G. Walldius,et al.  Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss. , 1989, International journal of obesity.

[97]  A. Kallner,et al.  Amino acid pattern in plasma before and after jejuno-ileal shunt operation for obesity. , 1975, Scandinavian journal of gastroenterology.

[98]  R. Pitts,et al.  The relation between plasma concentrations of glutamine and glycine and utilization of their nitrogens as sources of urinary ammonia. , 1966, The Journal of clinical investigation.

[99]  I. Penttila,et al.  Effect of insulin acid tolbutamide on blood citric acid in rabbits. , 1959, Scandinavian journal of clinical and laboratory investigation.

[100]  I. Penttilä,et al.  Effect of Insulin and Tolbutamide on Blood Citric Acid in Rabbits , 1959 .