Уважаемые пользователи!

Данный сайт содержит информацию для людей с медицинским образованием и специалистов здравоохранения.
Входя на сайт, Вы подтверждаете свое согласие с Условиями использования и Политикой конфиденциальности.

Dear visitor!
This site contains medical information for healthcare professionals.
You can go further, if you agree with Terms and Conditions and Privacy Policy on this site.

Adipokines: mechanisms of metabolic and behavioral disorders

Cover Page


Current studies show that metabolic and behavioral disorders represent severe health problems. Several questions arise about the molecular relationship of metabolic and behavioral disorders. This review will discuss the relationship of lipid metabolism and fructose consumption accompanied by an increase in weight as well as associated disorders: hypertension, insulin-resistance, oxidative stress and depression. Adipose tissue is considered as an endocrine tissue with intense secretory activities (metabolic and inflammatory). These adipokines are responsible for an alteration of several physiological functions. In this review we will try to understand how lipogenesis that causes dyslipidemia can influence insulin resistance, hypertension, oxidative stress, depression and the relationship between these various disorders.

Yassine Chahirou

Ibn Tofail University

Author for correspondence.
Email: yassine_chahirou@hotmail.fr
ORCID iD: 0000-0002-0755-8811

Morocco, Av. de L'Université, Kénitra

departement sciences of life

Abdelhalim Mesfioui

Ibn Tofail University

Email: a.mesfioui@yahoo.fr
ORCID iD: 0000-0002-1028-7469

Morocco, Av. de L'Université, Kénitra

Ali Ouichou

Ibn Tofail University

Email: ouichou@hotmail.com
ORCID iD: 0000-0001-9704-8526

Morocco, Av. de L'Université, Kénitra

Aboubaker Hessni

Ibn Tofail University

Email: elhessni70@yahoo.fr
ORCID iD: 0000-0003-4890-7069

Morocco, Av. de L'Université, Kénitra

  • Adams ST, Salhab M, Hussain ZI, et al. Obesity-related hypertension and its remission following gastric bypass surgery – A review of the mechanisms and predictive factors. Blood Press. 2012;22(3):131-137. doi: 10.3109/08037051.2012.749570.
  • Andersen RE. The spread of the childhood obesity epidemic. CMAJ. 2000;163(11):1461-1462. PMC80413.
  • - Douard V, Ferraris RP. Regulation of the fructose transporter GLUT5 in health and disease. American Journal of Physiology-Endocrinology and Metabolism. 2008;295(2):E227-E237. doi: 10.1152/ajpendo.90245.2008.
  • Heinz F, Lamprecht W, Kirsch J. Enzymes of fructose metabolism in human liver. J. Clin. Invest. 1968;47(8):1826-1832. doi: 10.1172/jci105872.
  • Mayes PA. Intermediary metabolism of fructose. The American Journal of Clinical Nutrition. 1993;58(5):754S-765S. doi: 10.1093/ajcn/58.5.754S.
  • Parks EJ, Skokan LE, Timlin MT, Dingfelder CS. Dietary Sugars Stimulate Fatty Acid Synthesis in Adults. The Journal of Nutrition. 2008;138(6):1039-1046. doi: 10.1093/jn/138.6.1039.
  • Basciano H, Federico L, Adeli K. Fructose, insulin resistance and metabolic dyslipidemia Nutr. Metab. 2005;2(1):5. doi: 10.1186/1743-7075-2-5.
  • Lê K-A, Tappy L. Metabolic effects of fructose. Curr. Opin. Clin. Nutr. Metab. Care. 2006;9(4):469-475. doi: 10.1097/01.mco.0000232910.61612.4d.
  • Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr. Rev. 2005;63(5):133-157.
  • Brasaemle DL. Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J. Lipid Res. 2007;48(12):2547-2559. doi: 10.1194/jlr.R700014-JLR200.
  • Foretz M, Carling D, Guichard C, et al. AMP-activated Protein Kinase Inhibits the Glucose-activated Expression of Fatty Acid Synthase Gene in Rat Hepatocytes. J. Biol. Chem. 1998;273(24):14767-14771. doi: 10.1074/jbc.273.24.14767.
  • Foretz M, Ancellin N, Andreelli F, et al. Short-Term Overexpression of a Constitutively Active Form of AMP-Activated Protein Kinase in the Liver Leads to Mild Hypoglycemia and Fatty Liver. Diabetes. 2005;54(5):1331-1339. doi: 10.2337/diabetes.54.5.1331.
  • Denu JM. Linking chromatin function with metabolic networks: Sir2 family of NAD+-dependent deacetylases. Trends Biochem. Sci. 2003;28(1):41-48. doi: 10.1016/s0968-0004(02)00005-1.
  • Lafontan M. Advances in adipose tissue metabolism. Int. J. Obes. 2009;32(S7):S39-S51. doi: 10.1038/ijo.2008.237.
  • Davies BSJ, Beigneux AP, Barnes RH, et al. GPIHBP1 Is Responsible for the Entry of Lipoprotein Lipase into Capillaries. Cell Metab. 2010;12(1):42-52. doi: 10.1016/j.cmet.2010.04.016.
  • Votruba SB, Jensen MD. Regional Fat Deposition as a Factor in FFA Metabolism. Annu. Rev. Nutr. 2007;27(1):149-163. doi: 10.1146/annurev.nutr.27.061406.093754.
  • Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res. 2009;48(5):275-297. doi: 10.1016/j.plipres.2009.05.001.
  • Lafontan M, Moro C, Berlan M, et al. Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol. Metab. 2008;19(4):130-137. doi: 10.1016/j.tem.2007.11.006.
  • Stich V, De Glisezinski I, Crampes F, et al. Activation of α2-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2000;279(2):R499-R504. doi: 10.1152/ajpregu.2000.279.2.R499.
  • Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol. Metab. 2000;11(8):327-332.
  • Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br. J. Nutr. 2007;92(03):347. doi: 10.1079/bjn20041213.
  • ClÉMent K, Viguerie N, Poitou C, et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. The FASEB Journal. 2004;18(14):1657-1669. doi: 10.1096/fj.04-2204com.
  • Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 2003;112(12):1796-1808. doi: 10.1172/jci200319246.
  • Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 2003;112(12):1821-1830. doi: 10.1172/jci200319451.
  • Sierra-Honigmann MR, Nath AK, Murakami C, et al. Biological action of leptin as an angiogenic factor. Science. 1998;281(5383):1683-1686.
  • Imparl-Radosevich J, Deas S, Polansky MM, et al. Regulation of PTP-1 and Insulin Receptor Kinase by Fractions from Cinnamon: Implications for Cinnamon Regulation of Insulin Signalling. Horm. Res. Paediatr. 1998;50(3):177-182. doi: 10.1159/000023270.
  • Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased p85/55/50 Expression and Decreased Phosphotidylinositol 3-Kinase Activity in Insulin-Resistant Human Skeletal Muscle. Diabetes. 2005;54(8):2351-2359. doi: 10.2337/diabetes.54.8.2351.
  • Hotamisligil G kS, Peraldi P, Budavari A, et al. IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-alpha- and Obesity-Induced Insulin Resistance. Science. 1996;271(5249):665-670. doi: 10.1126/science.271.5249.665.
  • Messerli FH. Cardiovascular effects of obesity and hypertension. Lancet. 1982;1(8282):1165-1168.
  • Grundy SM. Atherogenic dyslipidemia associated with metabolic syndrome and insulin resistance. Clin. Cornerstone. 2006;8 Suppl 1:S21-27.
  • Reaven GM. THE INSULIN RESISTANCE SYNDROME: Definition and Dietary Approaches to Treatment. Annu. Rev. Nutr. 2005;25(1):391-406. doi: 10.1146/annurev.nutr.24.012003.132155.
  • Hardie DG. AMPK and Raptor: Matching Cell Growth to Energy Supply. Mol. Cell. 2008;30(3):263-265. doi: 10.1016/j.molcel.2008.04.012.
  • Halliwell B. Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 2006;97(6):1634-1658. doi: 10.1111/j.1471-4159.2006.03907.x.
  • Balaban RS, Nemoto S, Finkel T. Mitochondria, Oxidants, and Aging. Cell. 2005;120(4):483-495. doi: 10.1016/j.cell.2005.02.001.
  • Lotharius J, Brundin P. Pathogenesis of parkinson's disease: dopamine, vesicles and α-synuclein. Nature Reviews Neuroscience. 2002;3(12):932-942. doi: 10.1038/nrn983.
  • Maes M, Song C, Lin A, et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine. 1998;10(4):313-318.
  • Raison CL, Demetrashvili M, Capuron L, Miller AH. Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs. 2005;19(2):105-123. PMC1255968.
  • Jessop DS, Dallman MF, Fleming D, Lightman SL. Resistance to Glucocorticoid Feedback in Obesity. J. Clin. Endocr. Metab. 2001;86(9):4109-4114. doi: 10.1210/jcem.86.9.7826.
  • Anacker C, Zunszain PA, Carvalho LA, Pariante CM. The glucocorticoid receptor: Pivot of depression and of antidepressant treatment? Psychoneuroendocrinology. 2011;36(3):415-425. doi: 10.1016/j.psyneuen.2010.03.007.
  • Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24-31. doi: 10.1016/j.it.2005.11.006.
  • Pittenger C, Duman RS. Stress, Depression and Neuroplasticity: A Convergence of Mechanisms. Neuropsychopharmacology. 2007;33(1):88-109. doi: 10.1038/sj.npp.1301574.
  • Maes M, Schotte C, Scharpé S, et al. The effects of glucocorticoids on the availability of L-tryptophan and tyrosine in the plasma of depressed patients. J. Affect. Disord. 1990;18(2):121-127. doi: 10.1016/0165-0327(90)90068-j.
  • Markus CR, Olivier B, Panhuysen GEM, et al. The bovine protein α-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress. The American Journal of Clinical Nutrition. 2000;71(6):1536-1544. doi: 10.1093/ajcn/71.6.1536.
  • Roy EJ, Takikawa O, Kranz DM, et al. Neuronal localization of indoleamine 2,3-dioxygenase in mice. Neurosci. Lett. 2005;387(2):95-99. doi: 10.1016/j.neulet.2005.07.010.
  • Guillemin GJ, Smythe G, Takikawa O, Brew BJ. Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons. Glia. 2005;49(1):15-23. doi: 10.1002/glia.20090.
  • Frenois F, Moreau M, O’Connor J, et al. Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology. 2007;32(5):516-531. doi: 10.1016/j.psyneuen.2007.03.005.
  • Stone TW, Darlington LG. Endogenous kynurenines as targets for drug discovery and development. Nature Reviews Drug Discovery. 2002;1(8):609-620. doi: 10.1038/nrd870.
  • Moyer BJ, Rojas IY, Kerley-Hamilton JS, et al. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1. Toxicol. Appl. Pharmacol. 2016;300:13-24. doi: 10.1016/j.taap.2016.03.011.
  • Yu E, Ruiz-Canela M, Guasch-Ferré M, et al. Increases in Plasma Tryptophan Are Inversely Associated with Incident Cardiovascular Disease in the Prevención con Dieta Mediterránea (PREDIMED) Study. The Journal of Nutrition. 2017:jn241711. doi: 10.3945/jn.116.241711.
  • Mudry JM, Alm PS, Erhardt S, et al. Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes. Diabetes Metab. Res. Rev. 2016;32(7):754-761. doi: 10.1002/dmrr.2798.
  • Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 2003;112(12):1796-1808. doi: 10.1172/jci200319246.
  • Eom T-Y, Jope RS. Blocked Inhibitory Serine-Phosphorylation of Glycogen Synthase Kinase-3α/β Impairs In Vivo Neural Precursor Cell Proliferation. Biol. Psychiatry. 2009;66(5):494-502. doi: 10.1016/j.biopsych.2009.04.015.
  • Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-643. doi: 10.1038/35007508.

Supplementary files

Supplementary Files Action
1. Fig. 1. Capture of fatty acids from chylomicrons and cholesterol derived from very low density lipoproteins (VLDL / VLDL). View (156KB) Indexing metadata
2. Fig. 2. Control of lipolysis and lipogenesis by natriuretic peptides, catecholamines and insulin: natriuretic peptides and catecholamines stimulate lipolysis by activating hormone-sensitive lipase (GLL / HSL), while insulin is a powerful inhibitor of lipolysis, reducing the activation of GLF. View (156KB) Indexing metadata
3. Fig. 3. Development of insulin resistance due to adipokines. View (50KB) Indexing metadata
4. Fig. 4. The formation of free radicals in the process of cellular respiration: a schematic representation of the formation of free radicals, excessive production of NADH (nicotinamide adenine dinucleotide) and FADH2 (flavin adenine dinucleotide) leads to dysfunction of complexes I and III, which is accompanied by excessive release of O2- (superoxide anion). View (70KB) Indexing metadata
5. Fig. 5. The role of adipokines in the development of behavioral disorders: (A) a schematic representation of the effect of insulin and leptin on behavior. (B) Schematic representation of the effect of cytokines on behavior. View (162KB) Indexing metadata


Abstract - 33

PDF (Russian) - 38

Copyright (c) 2018 Chahirou Y., Mesfioui A., Ouichou A., Hessni A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.