Leptin resistance: unsolved diagnostic issues

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Leptin and its receptors are key regulators of body weight and energy homeostasis. A decrease in tissue sensitivity to leptin leads to the development of obesity, insulin resistance, dyslipidemia, etc. Currently, the phenomenon of leptin resistance is explained by a number of mechanisms, including impairment of gene structure, leptin transport through the blood-brain barrier, and leptin receptor signaling. However, it is not known, a decrease in the number of receptors of which area leads to the development of leptin resistance. No relationship has been found between the basal leptin level in obesity and expression of leptin receptors in the skeletal muscles. It is also important to investigate the contribution of fatty tissue of different localization to leptin secretion regulation and activity of its receptors. The term «leptin resistence» reflects a complex pathophysiological phenomenon with broad perspectives for study. In this review, we analyze methods of diagnosing leptin resistance.

Keywords:

leptin

leptin receptors

leptin resistance

Authors:

Borodkina D.A.

GBOU VPO "Kemerovskaia gosudarstvennaia meditsinskaia akademiia"

Gruzdeva O.V.

Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia;
Kemerovo State Medical Academy, Kemerovo, Russia

Akbasheva O.E.

Siberian state medical university, Tomsk, Russia

Belik E.V.

Research institute for complex issues of cardiovascular diseases, Kemerovo, Russia

Palicheva E.I.

Research institute for complex issues of cardiovascular diseases, Kemerovo, Russia;
Kemerovo state medical university, Kemerovo, Russia

Barbarash O.L.

Kemerovskaia oblastnaia klinicheskaia bol'nitsa

SPIN RSCI: 5373-7620
Scopus AuthorID: 56699731800
ResearcherID: A-4834-2017
ORCID: 0000-0002-4642-3610

List of references:

Samorodskaya IV, Kondrikova NV. Cardiovascular disease and obesity. The possibility of bariatric surgery. Complex problems of serdechno-sosudistyh zabolevanij, 2015; (3): 53-60. (In Russ.)
Morioka T, Mori K, Motoyama K, et al. Ectopic fat accumulation and glucose homeostasis: role of leptin in glucose and lipid metabolism and mass maintenance in skeletal muscle. Musculoskeletal Disease Associated with Diabetes Mellitus. Springer Japan. 2016;201-213. doi:10.1007/978-4-431-55720-3_14
Аmetov AS, Аbdulkadirova FR, Pokrovskaya RA, et al The obesity: the role of leptin. Lechenie i profilaktika. 2014;2:86-91. (In Russ.)
Banks WA, William A. Role of the blood-brain barrier in the evolution of feeding and cognition. Annals of the New York Academy of Sciences. 2012;1264:13-19. doi:10.111/j.1749-6632.2012.06568.x
Malli F, Papaioannou AI, Gourgoulianis KI, et al. The role of leptin in the respiratory system: an overview. Respiratory Research. 2010;11(1):152. doi:10.1111/j.1749-6632.2012.06568.x
Osborn O, Sanchez-Alavez M, Brownell SE, et al. Metabolic characterization of a mouse deficient in all known leptin receptor isoforms. Cellular and molecular neurobiology. 2010;30(1): 23-33. doi:10.1007/s10571-009-9427-x
Paz-Filho G, Mastronardi CA, Licinio J. Leptin treatment: facts and expectations. Metabolism. 2015;64(1):146-156. doi:10.1016/j.metabol.2014.07.014
Gruzdeva OV, Akbasheva OE, Borodkina DA. et al. The Interrelation of indicators augy-rhenium and adipokines with the risk of diabetes type 2 a year after the PE-renesansa myocardial infarction. Rossijskij kardiologicheskij zhurnal. 2015;120(4):59-67. (In Russ.)
Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. Journal of Heredit. 1950 Dec;41(12):317-318. doi:10.1093/oxfordjournals.jhered.a106073
Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia. 1973;9:294-298. doi:10.1007/BF01221857
Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372(6505):425-432. doi:10.1038/372425a0
Crujeiras AB, Carreira MC, Cabia B, et al. Leptin resistance in obesity: an epigenetic landscape. Life Sciences. 2015;140:57-63. doi:10.1016/j.lfs.2015.05.003
Kosteli A, Sugaru E, Haemmerle G, et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. The Journal of clinical investigation. 2010;120(10):3466-3479. doi:10.1172/JCI42845
Considine RV, Considine EL, Williams CJ, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest. 1995;95:2986-2988.10 doi: 10.1172/JCI118007
Miyoshi Y, Funahashi T, Tanaka S, et al. High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels. International journal of cancer. 2005;118(6):1414-1419. doi:10.1002/ijc.21543
Kilpeläinen TO, Carli JFM, Skowronski AA, et al. Genome-wide metaanalysis uncovers novel loci influencing circulating leptin levels. Nature communications. 2016;7:10494. doi:10.1038/ncomms10494
Farooqi IS, O’Rahilly S. 20 years of leptin: human disorders of leptin action. Journal of Endocrinology. 2014;223(1):T63-T70. doi:10.1530/JOE-14-0480
Wada N, Hirako S, Takenoya F, et al. Leptin and its receptors. Journal of chemical neuroanatomy. 2014;61:191-199. doi:10.1016/j.jchemneu.2014.09.002
Tsai PJS, Davis J, Bryant-Greenwood G. Systemic and placental leptin and its receptors in pregnancies associated with obesity. Reproductive Sciences. 2014;22(2):189-197. doi:10.1177/1933719114537718
Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. Obesity Research & Clinical Practice. 2011;5:15. doi:10.1016/j.orcp.2011.08.082
Caro JF, Sinha MK, Kolaczynski JW, et al. Leptin: the tale of an obesity gene. Diabetes. 1996;45(11):1455-1462. doi:10.2337/diab.45.11.1455
Fischer-Posovszky P, Funcke JB, Wabitsch M. Biologically inactive leptin and early-onset extreme obesity. New England Journal of Medicine. 2015;372(1):48-54. doi:10.1056/NEJMoa1406653
Friedman J. 20 years of leptin: leptin at 20: an overview. Journal of endocrinology. 2014;223(1):T1-T8. doi:10.1530/JOE-14-0405
Chumakov GA, Ott AV, Veselovskaya NG, et al. Patogeneticheskie mekhanizmy leptinorezistentnosti. Rossijskij kardiologicheskij zhurnal. 2015;4:107-110. (In Russ.)
Philbrick KA, Wong CP, Branscum AJ, et al. Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism. Journal of Endocrinology. 2017;232(3):461-474. doi:10.1530/JOE-16-0484
Mainardi M, Pizzorusso T, Maffei M. Environment, leptin sensitivity, and hypothalamic plasticity. Neural plasticity. 2013;8. doi:10.1155/2013/438072
Miller AA. Deconstructing Normal: Leptin Variation Across and Within Population [dissertation]. Northwestern University; 2013.
Zhang Y, Ren J. Leptin and Obesity. Obesity. 2016;45-58. doi:10.1007/978-3-319-19821-7_4
Gonzalez-Carter D, Goode AE, Fiammengo R, et al. Inhibition of leptin-ObR interaction does not prevent leptin translocation across a human blood-brain Barrier model. Journal of Neuroendocrinology. 2016;28(6). doi:10.1111/jne.12392
Kovarenko MA, Ruyatkina LA, Petrishcheva MS, et al. Leptin: fiziologicheskie i patologicheskie aspekty deistviya. Vestnik NGU. Seriya: Biologiya, klinicheskaya meditsina. 2003;1(1):59-74. (In Russ.)
Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Annals of Internal Medicine.1999;130(8):671. doi:10.7326/0003-4819-130-8-199904200-00014
Scarpace PJ, Zhang Y. Leptin resistance: a prediposing factor for diet-induced obesity. Am J Physiol Regul Integr Comp Physiol. 2008;296:R493-R500. doi:10.1152/ajpregu.90669.2008
Posey KA, Clegg DJ, Printz RL, et al. Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. American Journal of Physiology Endocrinology and Metabolism. 2008;296:E1003-E1012. doi:10.1152/ajpendo.90377.2008
Zubiría MG, Vidal-Bravo J, Spinedi E, et al. Relationship between impaired adipogenesis of retroperitoneal adipose tissue and hypertrophic obesity: role of endogenous glucocorticoid excess. Journal of cellular and molecular medicine. 2014;18(8):1549-1561. doi:10.1111/jcmm.12308
Khan AR, Awan FR. Leptin resistance: a possible interface between obesity and pulmonary-related disorders. International journal of endocrinology and metabolism. 2016;14(1). doi:10.5812/ijem.32586
Münzberg H, Heymsfield SB. Leptin, obesity, and leptin resistance. Leptin. 2014;67-78. doi:10.1007/978-3-319-09915-6_6
Lonnqvist F, Arner P, Nordfors L. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med. 1995;1:950-953. doi:10.1038/nm0995-950
Silha JV, Krsek M, Skrha JV, et al. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. European Journal of Endocrinology. 2003;149(4);331-335. doi:10.1530/eje.0.1490331
Ravussin Y, LeDuc CA, Watanabe K, et al. Effects of chronic leptin infusion on subsequent body weight and composition in mice: Can body weight set point be reset? Molecular metabolism. 2014;3(4):432-440. doi:10.1016/j.molmet.2014.02.003
Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292-295. doi:10.1056/NEJM199602013340503
Schaab M, Kratzsch J. The soluble leptin receptor. Best Practice & Research Clinical Endocrinology & Metabolism. 2015;29(5):661-670. doi:10.1016/j.beem.2015.08.002
Groba C, Mayerl S, van Mullem AA, et al. Hypothyroidism compromises hypothalamic leptin signaling in mice. Molecular Endocrinology. 2013;27(4):586-597. doi:10.1210/me.2012-1311
Nejati-Koshki K, Akbarzadeh A, Pourhasan-Moghaddam M, et al. Inhibition of leptin and leptin receptor gene expression by silibinin-curcumin combination. Asian Pacific Journal of Cancer Prevention. 2013;14(11):6595-6599. doi:10.7314/APJCP.2013.14.11.6595
de Queiroz KB, Guimaraes JB, Coimbra CC, et al. Endurance training increases leptin expression in the retroperitoneal adipose tissue of rats fed with a high-sugar diet. Lipids. 2013;49(1):85-96. doi:10.1007/s11745-013-3854-7
Lana A, Valdés-Bécares A, Buño A, et al. Serum leptin concentration is associated with incident frailty in older adults. Aging and Disease. 2017;8(2):240. doi:10.14336/AD.2016.0819
Zhang J, Scarpace PJ. The soluble leptin receptor neutralizes leptin-mediated STAT3 signalling and anorexic responses in vivo. Br J Pharmacol. 2009;158:475-482. doi:10.1111/j.1476-5381.2009.00246.x
Baranowska-Bik A, Bik W, Styczynska M, et al. Plasma leptin levels and free leptin index in women with Alzheimer’s disease. Neuropeptides. 2015;52:73-78. doi:10.1016/j.npep.2015.05.006
Rizk NM, Sharif E. Leptin as well as free leptin receptor is associated with polycystic ovary syndrome in young women. International journal of endocrinology. 2015;1-10. doi:10.1155/2015/927805
Jacquier M, Soula HA, Crauste F. A mathematical model of leptin resistance. Mathematical biosciences. 2015;267:10-23. doi:10.1016/j.mbs.2015.06.008
Murugesan D, Arunachalam T, Ramamurthy V, et al. Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore. Indian J Hum Genet. 2010;16(2):72-77. doi:10.4103/0971-6866.69350
Guerra B, once-González JG, Morales-Alamo D, et al. Leptin signaling in skeletal muscle after bed rest in healthy humans. European journal of applied physiology. 2013;114(2):345-357. doi:10.1007/s00421-013-2779-4
Gruzdeva OV, Akbasheva OE, Dylev YuA. Adipokine and cytokine Pro-Fili epicardial and subcutaneous adipose tissue in patients with coronary disease of the heart. Byulleten’ ehksperimental’noj biologii i mediciny. 2017;163(5):560-563. (In Russ.)

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