Effect of genistein with carnitine administration on lipid parameters and obesity in C57Bl/6J mice fed a high-fat diet.

Soy products are mainly composed of proteins, phytochemicals such as isoflavones, soy lipids, and carbohydrates. It is unclear whether an individual component alone or a combined effect of multiple bioactive compounds contributes to the beneficial properties of soy. We investigated the effect of dietary genistein (the principal soy isoflavone) alone and combined with L-carnitine to evaluate possible synergistic effects on the intentionally induced prediabetic state characterized by insulin resistance and obesity in C57Bl/6J mice fed a high-fat diet (HD). In the HD-alone group, abdominal and back fat relative to total body weight were significantly higher compared with other groups including those fed normal diet (ND). Among the HD groups, final weight gains of the HD plus genistein (HD+G) and HD plus genistein plus L-carnitine (HD+G+C) groups were lower compared with that of the control (HD-alone). Especially in liver, the results showed that genistein with carnitine transcriptionally up-regulated expressions of acyl-coenzyme A synthetase (ACS) and carnitine palmitoyltransferase-I (CPT-I) by approximately 50% and 40%, respectively, compared with genistein alone. However, the up-regulation of CPT-I did not directly reflect the enzyme activity of CPT-I. On the other hand, the effects of genistein and genistein with carnitine on the expressions of ACS and CPT-I in muscle were not significant. Our study suggests that genistein with carnitine exerts anti-obesity effects, probably by modulating peroxisome proliferator-activated receptor-associated genes. However, further work is needed to elucidate the possible mechanisms by which genistein and carnitine intervene.

[1]  M. Lazar,et al.  How Obesity Causes Diabetes: Not a Tall Tale , 2005, Science.

[2]  B. Schreiber,et al.  PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes , 2005 .

[3]  J Auwerx,et al.  Mechanism of action of fibrates on lipid and lipoprotein metabolism. , 1998, Circulation.

[4]  Jeremy E. Davis,et al.  Gene expression and adiposity are modified by soy protein in male Zucker diabetic fatty rats. , 2004, Obesity research.

[5]  G. Gil-Gómez,et al.  Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids. , 1994, The Journal of biological chemistry.

[6]  R. Elashoff,et al.  Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein , 2005, European Journal of Clinical Nutrition.

[7]  D. S. Sachan,et al.  Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver. , 1984, The American journal of clinical nutrition.

[8]  W. James,et al.  Diabetes and hypertension increases in a society with abdominal obesity: results of the Mexican National Health Survey 2000. , 2005 .

[9]  J. Grande,et al.  Weight-cycling decreases incidence and increases latency of mammary tumors to a greater extent than does chronic caloric restriction in mouse mammary tumor virus-transforming growth factor-alpha female mice. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[10]  J. Kim,et al.  Genistein enhances expression of genes involved in fatty acid catabolism through activation of PPARα , 2004, Molecular and Cellular Endocrinology.

[11]  Diet-induced obesity delays cardiovascular recovery from stress in spontaneously hypertensive rats. , 2004, Obesity research.

[12]  P. Fu,et al.  Enzymatic determination of total serum cholesterol. , 1974, Clinical chemistry.

[13]  S. Ho,et al.  Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. , 2005, The American journal of clinical nutrition.

[14]  A. Császár.  Hypertriglyceridemia, the coronary heart disease risk marker "solved". , 2005, Acta physiologica Hungarica.

[15]  T. Aoyama,et al.  Soy protein isolate and its hydrolysate reduce body fat of dietary obese rats and genetically obese mice (yellow KK) , 2000, Nutrition.

[16]  J. Ha,et al.  Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. , 2005, Biochemical and biophysical research communications.

[17]  D. Rudman,et al.  Role of carnitine in human nutrition. , 1988, The Journal of nutrition.

[18]  J. Cha,et al.  Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and beta-oxidation of fatty acid in OLETF rats. , 2001, Nutrition.

[19]  A. Stunkard,et al.  Depression and obesity , 2003, Biological Psychiatry.

[20]  Chin-Lin Hsu,et al.  Phenolic compounds: evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms. , 2008, Molecular nutrition & food research.

[21]  H. Lardy,et al.  [15] Isolation of liver or kidney mitochondria , 1967 .

[22]  A. Stunkard,et al.  Binge eating disorder: disorder or marker? , 2003, The International journal of eating disorders.

[23]  G. Velasco,et al.  Role of Carnitine Palmitoyltransferase I in the Control of Ketogenesis in Primary Cultures of Rat Astrocytes , 1998, Journal of neurochemistry.

[24]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[25]  W. Banz,et al.  Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. , 2003, The Journal of nutrition.

[26]  J. Bremer.  Carnitine in intermediary metabolism. Reversible acetylation of carnitine by mitochondria. , 1962, The Journal of biological chemistry.

[27]  L. Istasse,et al.  Influence of obesity on plasma lipid and lipoprotein concentrations in dogs. , 2005, American journal of veterinary research.

[28]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[29]  G. Reach,et al.  PPAR-α–Null Mice Are Protected From High-Fat Diet–Induced Insulin Resistance , 2001 .

[30]  W. Banz,et al.  In vitro effects of soy phytoestrogens on rat L6 skeletal muscle cells. , 2005, Journal of medicinal food.

[31]  J. Viikari,et al.  Serum leptin concentration poorly reflects growth and energy and nutrient intake in young children. , 2004, Pediatrics.

[32]  S. Lindstedt,et al.  A method for the determination of carnitine in the picomole range. , 1972, Clinica chimica acta; international journal of clinical chemistry.

[33]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[34]  M. Guzmán,et al.  Ethanol feeding to rats reversibly decreases hepatic carnitine palmitoyltransferase activity and increases enzyme sensitivity to malonyl-CoA. , 1987, Biochemical and biophysical research communications.

[35]  H. Kim,et al.  Screening of Differentially Expressed Genes by Desferrioxamine or Ferric Ammonium Citrate Treatment in HepG2 Cells , 2000 .

[36]  A. Stunkard,et al.  Two forms of disordered eating in obesity: binge eating and night eating , 2003, International Journal of Obesity.

[37]  E. Pruszyńska‐Oszmałek,et al.  Genistein restricts leptin secretion from rat adipocytes , 2005, The Journal of Steroid Biochemistry and Molecular Biology.