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01.06.2019 | Review Article

SOCS3 as a future target to treat metabolic disorders

verfasst von: João A.B. Pedroso, Angela M. Ramos-Lobo, Jose Donato Jr

Erschienen in: Hormones | Ausgabe 2/2019

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Abstract

The suppressors of cytokine signaling (SOCS) are a group of eight proteins responsible for preventing excessive cytokine signaling. Among this protein family, SOCS3 has received special attention. SOCS3 expression is important to control certain allergy autoimmune diseases. Furthermore, SOCS3 expression is elevated in obesity and it is involved in the inhibition of leptin and insulin signaling, two important hormones involved in the control of energy metabolism. Therefore, increased SOCS3 expression in obese individuals is associated with several metabolic disorders, including reduced energy expenditure, increased food intake and adiposity, and insulin and leptin resistance. In addition, recent studies found that SOCS3 expression regulates energy and glucose homeostasis in several metabolic conditions, such as pregnancy, caloric restriction, and refeeding. Importantly, attenuation of SOCS3 expression in most cases improves leptin and insulin sensitivity, leading to beneficial metabolic effects. This review aims to discuss the role of SOCS3 in the control of blood glucose levels as well as in energy homeostasis. The development of pharmacological compounds to inhibit SOCS3 activity and/or expression may represent a promising therapeutic approach to treat type 2 diabetes mellitus, obesity, and other metabolic imbalances.

Yoshimura A, Naka T, Kubo M (2007) SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol 7(6):454–465. https://doi.org/10.1038/nri2093 CrossRefPubMed

Krebs DL, Hilton DJ (2001) SOCS proteins: negative regulators of cytokine signaling. Stem Cells 19(5):378–387. https://doi.org/10.1634/stemcells.19-5-378 CrossRefPubMed

Howard JK, Flier JS (2006) Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol Metab 17(9):365–371. https://doi.org/10.1016/j.tem.2006.09.007 CrossRefPubMed

Yin Y, Liu W, Dai Y (2015) SOCS3 and its role in associated diseases. Hum Immunol 76(10):775–780. https://doi.org/10.1016/j.humimm.2015.09.037 CrossRefPubMed

Wong PK, Egan PJ, Croker BA, O'Donnell K, Sims NA, Drake S, Kiu H, McManus EJ, Alexander WS, Roberts AW, Wicks IP (2006) SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest 116(6):1571–1581. https://doi.org/10.1172/JCI25660 CrossRefPubMedPubMedCentral

Shouda T, Yoshida T, Hanada T, Wakioka T, Oishi M, Miyoshi K, Komiya S, Kosai K, Hanakawa Y, Hashimoto K, Nagata K, Yoshimura A (2001) Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J Clin Invest 108(12):1781–1788. https://doi.org/10.1172/JCI13568 CrossRefPubMedPubMedCentral

Calegari VC, Bezerra RM, Torsoni MA, Torsoni AS, Franchini KG, Saad MJ, Velloso LA (2003) Suppressor of cytokine signaling 3 is induced by angiotensin II in heart and isolated cardiomyocytes, and participates in desensitization. Endocrinology 144(10):4586–4596. https://doi.org/10.1210/en.2003-0046 CrossRefPubMed

Ferrario CM (2006) Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renin-Angiotensin-Aldosterone Syst 7(1):3–14. https://doi.org/10.3317/jraas.2006.003 CrossRefPubMed

Agha M, Agha R (2017) The rising prevalence of obesity: part a: impact on public health. International journal of surgery Oncology 2(7):e17. https://doi.org/10.1097/IJ9.0000000000000017 CrossRefPubMedPubMedCentral

10.

Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C (2018) Obesity as a disease. Med Clin North Am 102(1):13–33. https://doi.org/10.1016/j.mcna.2017.08.004 CrossRefPubMed

11.

Palanivel R, Fullerton MD, Galic S, Honeyman J, Hewitt KA, Jorgensen SB, Steinberg GR (2012) Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance. Diabetologia 55(11):3083–3093. https://doi.org/10.1007/s00125-012-2665-3 CrossRefPubMedPubMedCentral

12.

Pedroso JA, Buonfiglio DC, Cardinali LI, Furigo IC, Ramos-Lobo AM, Tirapegui J, Elias CF, Donato J Jr (2014) Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity. Mol Metab 3(6):608–618. https://doi.org/10.1016/j.molmet.2014.06.001 CrossRefPubMedPubMedCentral

13.

Zampieri TT, da Silva TE, de Paula Romeu D, Torrao AS, Donato J Jr (2016) SOCS3 expression within leptin receptor-expressing cells regulates food intake and leptin sensitivity but does not affect weight gain in pregnant mice consuming a high-fat diet. Physiol Behav 157:109–115. https://doi.org/10.1016/j.physbeh.2016.01.039 CrossRefPubMed

14.

Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS (1998) Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1(4):619–625CrossRefPubMed

15.

Santillan-Benitez JG, Mendieta-Zeron H, Gomez-Olivan LM, Quiroz AO, Torres-Juarez JJ, Gonzalez-Banales JM (2014) JAK2, STAT3 and SOCS3 gene expression in women with and without breast cancer. Gene 547(1):70–76. https://doi.org/10.1016/j.gene.2014.06.025 CrossRefPubMed

16.

Ahima RS, Stanley TL, Khor VK, Zanni MV, Grinspoon SK (2011) Estrogen sulfotransferase is expressed in subcutaneous adipose tissue of obese humans in association with TNF-alpha and SOCS3. J Clin Endocrinol Metab 96(7):E1153–E1158. https://doi.org/10.1210/jc.2010-2903 CrossRefPubMedPubMedCentral

17.

Xu K, Zhang X, Wang Z, Hu Y, Sinha R (2018) Epigenome-wide association analysis revealed that SOCS3 methylation influences the effect of cumulative stress on obesity. Biol Psychol 131:63–71. https://doi.org/10.1016/j.biopsycho.2016.11.001 CrossRefPubMed

18.

Zhou Y, Rui L (2013) Leptin signaling and leptin resistance. Front Med 7(2):207–222. https://doi.org/10.1007/s11684-013-0263-5 CrossRefPubMedPubMedCentral

19.

Lubis AR, Widia F, Soegondo S, Setiawati A (2008) The role of SOCS-3 protein in leptin resistance and obesity. Acta Med Indones 40(2):89–95PubMed

20.

Emanuelli B, Peraldi P, Filloux C, Chavey C, Freidinger K, Hilton DJ, Hotamisligil GS, Van Obberghen E (2001) SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-alpha in the adipose tissue of obese mice. J Biol Chem 276(51):47944–47949. https://doi.org/10.1074/jbc.M104602200 CrossRefPubMed

21.

Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E (2000) SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem 275(21):15985–15991CrossRefPubMed

22.

Klok MD, Jakobsdottir S, Drent ML (2007) The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 8(1):21–34. https://doi.org/10.1111/j.1467-789X.2006.00270.x CrossRefPubMed

23.

Shimizu H, Oh IS, Okada S, Mori M (2007) Leptin resistance and obesity. Endocr J 54(1):17–26CrossRefPubMed

24.

El-Haschimi K, Lehnert H (2003) Leptin resistance - or why leptin fails to work in obesity. Exp Clin Endocrinol Diabetes 111(1):2–7. https://doi.org/10.1055/s-2003-37492 CrossRefPubMed

25.

Guo S (2014) Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. J Endocrinol 220(2):T1–T23. https://doi.org/10.1530/JOE-13-0327 CrossRefPubMedPubMedCentral

26.

Rui L, Yuan M, Frantz D, Shoelson S, White MF (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 277(44):42394–42398. https://doi.org/10.1074/jbc.C200444200 CrossRefPubMed

27.

Zampieri TT, Ramos-Lobo AM, Furigo IC, Pedroso JA, Buonfiglio DC, Donato J Jr (2015) SOCS3 deficiency in leptin receptor-expressing cells mitigates the development of pregnancy-induced metabolic changes. Molecular metabolism 4(3):237–245. https://doi.org/10.1016/j.molmet.2014.12.005 CrossRefPubMed

28.

Pedroso JA, Silveira MA, Lima LB, Furigo IC, Zampieri TT, Ramos-Lobo AM, Buonfiglio DC, Teixeira PD, Frazao R, Donato J Jr (2016) Changes in leptin signaling by SOCS3 modulate fasting-induced Hyperphagia and weight regain in mice. Endocrinology 157(10):3901–3914. https://doi.org/10.1210/en.2016-1038 CrossRefPubMed

29.

Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A (2004) Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10(7):739–743. https://doi.org/10.1038/nm1071 CrossRefPubMed

30.

Jorgensen SB, O'Neill HM, Sylow L, Honeyman J, Hewitt KA, Palanivel R, Fullerton MD, Oberg L, Balendran A, Galic S, van der Poel C, Trounce IA, Lynch GS, Schertzer JD, Steinberg GR (2013) Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes 62(1):56–64. https://doi.org/10.2337/db12-0443 CrossRefPubMed

31.

Ortega FB, Lavie CJ, Blair SN (2016) Obesity and cardiovascular disease. Circ Res 118(11):1752–1770. https://doi.org/10.1161/CIRCRESAHA.115.306883 CrossRefPubMed

32.

Lipek T, Igel U, Gausche R, Kiess W, Grande G (2015) Obesogenic environments: environmental approaches to obesity prevention. J Pediatr Endocrinol Metab 28(5–6):485–495. https://doi.org/10.1515/jpem-2015-0127 CrossRefPubMed

33.

Myers MG Jr, Olson DP (2012) Central nervous system control of metabolism. Nature 491(7424):357–363. https://doi.org/10.1038/nature11705 CrossRefPubMed

34.

Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404(6778):661–671. https://doi.org/10.1038/35007534 CrossRefPubMed

35.

Munzberg H, Myers MG, Jr. (2005) Molecular and anatomical determinants of central leptin resistance. Nat Neurosci 8 (5):566–570. doi:https://doi.org/10.1038/nn1454

36.

Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395(6704):763–770. https://doi.org/10.1038/27376 CrossRefPubMed

37.

Zhang YY, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homolog. Nature 372(6505):425–432. https://doi.org/10.1038/372425a0 CrossRefPubMed

38.

Kwon O, Kim KW, Kim MS (2016) Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci 73(7):1457–1477. https://doi.org/10.1007/s00018-016-2133-1 CrossRefPubMed

39.

Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM (1997) Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci U S A 94(16):8878–8883CrossRefPubMedPubMedCentral

40.

Reed AS, Unger EK, Olofsson LE, Piper ML, Myers MG Jr, Xu AW (2010) Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes 59(4):894–906. https://doi.org/10.2337/db09-1024 CrossRefPubMedPubMedCentral

41.

Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (1999) The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J 18 (5):1309–1320. doi:DOI 10.1093/emboj/18.5.1309

42.

Fruhbeck G (2006) Intracellular signalling pathways activated by leptin. Biochem. J. 393(Pt 1):7–20. https://doi.org/10.1042/BJ20051578 CrossRefPubMed

43.

Krol E, Speakman JR (2007) Regulation of body mass and adiposity in the field vole, Microtus agrestis: a model of leptin resistance. J Endocrinol 192(2):271–278. https://doi.org/10.1677/JOE-06-0074 CrossRefPubMed

44.

Norman JE, Reynolds RM (2011) The consequences of obesity and excess weight gain in pregnancy. Proc Nutr Soc 70(4):450–456. https://doi.org/10.1017/S0029665111003077 CrossRefPubMed

45.

Ladyman SR, Fieldwick DM, Grattan DR (2012) Suppression of leptin-induced hypothalamic JAK/STAT signalling and feeding response during pregnancy in the mouse. Reproduction 144(1):83–90. https://doi.org/10.1530/REP-12-0112 CrossRefPubMed

46.

Nagaishi VS, Cardinali LI, Zampieri TT, Furigo IC, Metzger M, Donato J Jr (2014) Possible crosstalk between leptin and prolactin during pregnancy. Neuroscience 259:71–83. https://doi.org/10.1016/j.neuroscience.2013.11.050 CrossRefPubMed

47.

Ayyad C, Andersen T (2000) Long-term efficacy of dietary treatment of obesity: a systematic review of studies published between 1931 and 1999. Obes Rev 1(2):113–119CrossRefPubMed

48.

Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels B, Chatman J (2007) Medicare's search for effective obesity treatments: diets are not the answer. Am Psychol 62(3):220–233. https://doi.org/10.1037/0003-066X.62.3.220 CrossRefPubMed

49.

Hambly C, Duncan JS, Archer ZA, Moar KM, Mercer JG, Speakman JR (2012) Repletion of TNFalpha or leptin in calorically restricted mice suppresses post-restriction hyperphagia. Dis Model Mech 5(1):83–94. https://doi.org/10.1242/dmm.007781 CrossRefPubMed

50.

Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjorbaek C, Flier JS (2004) Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med 10(7):734–738. https://doi.org/10.1038/nm1072 CrossRefPubMed

51.

Briancon N, McNay DE, Maratos-Flier E, Flier JS (2010) Combined neural inactivation of suppressor of cytokine signaling-3 and protein-tyrosine phosphatase-1B reveals additive, synergistic, and factor-specific roles in the regulation of body energy balance. Diabetes 59(12):3074–3084. https://doi.org/10.2337/db10-0481 CrossRefPubMedPubMedCentral

52.

Liu ZJ, Bian J, Zhao YL, Zhang X, Zou N, Li D (2011) Lentiviral vector-mediated knockdown of SOCS3 in the hypothalamus protects against the development of diet-induced obesity in rats. Diabetes Obes Metab 13(10):885–892. https://doi.org/10.1111/j.1463-1326.2011.01419.x CrossRefPubMed

53.

de Backer MW, Brans MA, van Rozen AJ, van der Zwaal EM, Luijendijk MC, Garner KG, de Krom M, van Beekum O, la Fleur SE, Adan RA (2010) Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance. J Mol Endocrinol 45(5):341–353. https://doi.org/10.1677/JME-10-0057 CrossRefPubMed

54.

Matarazzo V, Schaller F, Nedelec E, Benani A, Penicaud L, Muscatelli F, Moyse E, Bauer S (2012) Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. J Neurosci 32(48):17097–17107. https://doi.org/10.1523/JNEUROSCI.1669-12.2012 CrossRefPubMedPubMedCentral

55.

Kievit P, Howard JK, Badman MK, Balthasar N, Coppari R, Mori H, Lee CE, Elmquist JK, Yoshimura A, Flier JS (2006) Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab 4(2):123–132. https://doi.org/10.1016/j.cmet.2006.06.010 CrossRefPubMed

56.

Zhang R, Dhillon H, Yin H, Yoshimura A, Lowell BB, Maratos-Flier E, Flier JS (2008) Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology 149(11):5654–5661. https://doi.org/10.1210/en.2008-0805 CrossRefPubMedPubMedCentral

57.

Pedroso JAB, de Mendonca POR, Fortes MAS, Tomaz I, Pecorali VL, Auricino TB, Costa IC, Lima LB, Furigo IC, Bueno DN, Ramos-Lobo AM, Lotfi CFP, Donato J Jr (2017) SOCS3 expression in SF1 cells regulates adrenal differentiation and exercise performance. J Endocrinol 235(3):207–222. https://doi.org/10.1530/JOE-17-0255 CrossRefPubMed

58.

Ramos-Lobo AM, Teixeira PDS, Furigo IC, Donato J Jr (2017) SOCS3 ablation in SF1 cells causes modest metabolic effects during pregnancy and lactation. Neuroscience 365:114–124. https://doi.org/10.1016/j.neuroscience.2017.09.048 CrossRefPubMed

59.

Ramos-Lobo AM, Furigo IC, Teixeira PDS, Zampieri TT, Wasinski F, Buonfiglio DC, Donato J Jr (2018) Maternal metabolic adaptations are necessary for normal offspring growth and brain development. Phys. Rep. 6(5). https://doi.org/10.14814/phy2.13643

60.

Torisu T, Sato N, Yoshiga D, Kobayashi T, Yoshioka T, Mori H, Iida M, Yoshimura A (2007) The dual function of hepatic SOCS3 in insulin resistance in vivo. Genes Cells 12(2):143–154. https://doi.org/10.1111/j.1365-2443.2007.01044.x CrossRefPubMed

61.

Sachithanandan N, Fam BC, Fynch S, Dzamko N, Watt MJ, Wormald S, Honeyman J, Galic S, Proietto J, Andrikopoulos S, Hevener AL, Kay TW, Steinberg GR (2010) Liver-specific suppressor of cytokine signaling-3 deletion in mice enhances hepatic insulin sensitivity and lipogenesis resulting in fatty liver and obesity. Hepatology 52(5):1632–1642. https://doi.org/10.1002/hep.23861 CrossRefPubMed

62.

Bjorbaek C, El-Haschimi K, Frantz JD, Flier JS (1999) The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem 274(42):30059–30065CrossRefPubMed

63.

Ladyman SR, Augustine RA, Grattan DR (2010) Hormone interactions regulating energy balance during pregnancy. J Neuroendocrinol 22(7):805–817. https://doi.org/10.1111/j.1365-2826.2010.02017.x CrossRefPubMed

64.

Ladyman SR, Grattan DR (2005) Suppression of leptin receptor messenger ribonucleic acid and leptin responsiveness in the ventromedial nucleus of the hypothalamus during pregnancy in the rat. Endocrinology 146(9):3868–3874. https://doi.org/10.1210/en.2005-0194 CrossRefPubMed

65.

Ladyman SR, Grattan DR (2016) Central effects of leptin on glucose homeostasis are modified during pregnancy in the rat. J Neuroendocrinol 28(10). https://doi.org/10.1111/jne.12431

66.

Beauloye V, Willems B, de Coninck V, Frank SJ, Edery M, Thissen JP (2002) Impairment of liver GH receptor signaling by fasting. Endocrinology 143(3):792–800. https://doi.org/10.1210/endo.143.3.8692 CrossRefPubMed

67.

Ueki K, Kondo T, Kahn CR (2004) Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol 24(12):5434–5446. https://doi.org/10.1128/MCB.24.12.5434-5446.2004 CrossRefPubMedPubMedCentral

68.

Senn JJ, Klover PJ, Nowak IA, Zimmers TA, Koniaris LG, Furlanetto RW, Mooney RA (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278(16):13740–13746. https://doi.org/10.1074/jbc.M210689200 CrossRefPubMed

69.

Shi H, Tzameli I, Bjorbaek C, Flier JS (2004) Suppressor of cytokine signaling 3 is a physiological regulator of adipocyte insulin signaling. J Biol Chem 279(33):34733–34740. https://doi.org/10.1074/jbc.M403886200 CrossRefPubMed

70.

Yang Z, Hulver M, McMillan RP, Cai L, Kershaw EE, Yu L, Xue B, Shi H (2012) Regulation of insulin and leptin signaling by muscle suppressor of cytokine signaling 3 (SOCS3). PLoS One 7(10):e47493. https://doi.org/10.1371/journal.pone.0047493 CrossRefPubMedPubMedCentral

71.

Tups A, Benzler J, Sergi D, Ladyman SR, Williams LM (2017) Central regulation of glucose homeostasis. Compr Physiol 7(2):741–764. https://doi.org/10.1002/cphy.c160015 CrossRefPubMed

72.

Donato J Jr (2012) The central nervous system as a promising target to treat diabetes mellitus. Curr Top Med Chem 12(19):2070–2081CrossRefPubMed

73.

Havrankova J, Roth J, Brownstein M (1978) Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272(5656):827–829CrossRefPubMed

74.

Obici S, Zhang BB, Karkanias G, Rossetti L (2002) Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 8(12):1376–1382. https://doi.org/10.1038/nm798 CrossRefPubMed

75.

Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289(5487):2122–2125CrossRefPubMed

76.

Denroche HC, Huynh FK, Kieffer TJ (2012) The role of leptin in glucose homeostasis. J Diabetes Investig 3(2):115–129. https://doi.org/10.1111/j.2040-1124.2012.00203.x CrossRefPubMedPubMedCentral

77.

Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in Ob/Ob mice. Science 269(5223):540–543CrossRefPubMed

78.

Hedbacker K, Birsoy K, Wysocki RW, Asilmaz E, Ahima RS, Farooqi IS, Friedman JM (2010) Antidiabetic effects of IGFBP2, a leptin-regulated gene. Cell Metab 11(1):11–22. https://doi.org/10.1016/j.cmet.2009.11.007 CrossRefPubMed

79.

Hidaka S, Yoshimatsu H, Kondou S, Tsuruta Y, Oka K, Noguchi H, Okamoto K, Sakino H, Teshima Y, Okeda T, Sakata T (2002) Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. FASEB J 16(6):509–518. https://doi.org/10.1096/fj.01-0164com CrossRefPubMed

80.

Meek TH, Morton GJ (2012) Leptin, diabetes, and the brain Indian journal of endocrinology and metabolism. 16(Suppl 3):S534–S542. https://doi.org/10.4103/2230-8210.105568

81.

Pocai A, Morgan K, Buettner C, Gutierrez-Juarez R, Obici S, Rossetti L (2005) Central leptin acutely reverses diet-induced hepatic insulin resistance. Diabetes 54(11):3182–3189. https://doi.org/10.2337/diabetes.54.11.3182 CrossRefPubMed

82.

Seufert J (2004) Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 53(Suppl 1):S152–S158CrossRefPubMed

83.

Scheller EL, Hankenson KD, Reuben JS, Krebsbach PH (2011) Zoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production. J Cell Biochem 112(11):3364–3372. https://doi.org/10.1002/jcb.23267 CrossRefPubMedPubMedCentral

84.

Whitaker M, Guo J, Kehoe T, Benson G (2012) Bisphosphonates for osteoporosis--where do we go from here? N Engl J Med 366(22):2048–2051. https://doi.org/10.1056/NEJMp1202619 CrossRefPubMed

85.

He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5(7):522–531. https://doi.org/10.1038/nrg1379 CrossRefPubMed

86.

Soriano A, Jubierre L, Almazan-Moga A, Molist C, Roma J, de Toledo JS, Gallego S, Segura MF (2013) microRNAs as pharmacological targets in cancer. Pharmacol Res 75:3–14. https://doi.org/10.1016/j.phrs.2013.03.006 CrossRefPubMed

87.

Li Y, Luo T, Wang L, Wu J, Guo S (2016) MicroRNA-19a-3p enhances the proliferation and insulin secretion, while it inhibits the apoptosis of pancreatic beta cells via the inhibition of SOCS3. Int J Mol Med 38(5):1515–1524. https://doi.org/10.3892/ijmm.2016.2748 CrossRefPubMed

88.

Bao L, Fu X, Si M, Wang Y, Ma R, Ren X, Lv H (2015) MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes. PLoS One 10(2):e0116067. https://doi.org/10.1371/journal.pone.0116067 CrossRefPubMedPubMedCentral

89.

Davalos A, Suarez Y (2013) MiRNA-based therapy: from bench to bedside. Pharmacol Res 75:1–2. https://doi.org/10.1016/j.phrs.2013.06.010 CrossRefPubMed

90.

Nybo L (2003) CNS fatigue and prolonged exercise: effect of glucose supplementation. Med Sci Sports Exerc 35(4):589–594. https://doi.org/10.1249/01.MSS.0000058433.85789.66 CrossRefPubMed

91.

Fujikawa T, Castorena CM, Lee S, Elmquist JK (2017) The hypothalamic regulation of metabolic adaptations to exercise. J Neuroendocrinol 29(10). https://doi.org/10.1111/jne.12533

92.

Beltowski J, Wojcicka G, Marciniak A, Jamroz A (2004) Oxidative stress, nitric oxide production, and renal sodium handling in leptin-induced hypertension. Life Sci 74(24):2987–3000. https://doi.org/10.1016/j.lfs.2003.10.029 CrossRefPubMed

93.

Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest 100(2):270–278. https://doi.org/10.1172/JCI119532 CrossRefPubMedPubMedCentral

94.

Zhang DY, Anderson AS (2014) The sympathetic nervous system and heart failure. Cardiol Clin 32(1):33–45, vii. https://doi.org/10.1016/j.ccl.2013.09.010 CrossRefPubMedPubMedCentral

Titel: SOCS3 as a future target to treat metabolic disorders
verfasst von: João A.B. Pedroso
Angela M. Ramos-Lobo
Jose Donato Jr
Publikationsdatum: 01.06.2019
Verlag: Springer International Publishing
Erschienen in: Hormones / Ausgabe 2/2019
Print ISSN: 1109-3099
Elektronische ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-018-0078-5

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Methylation profile of genes involved in inflammation, in the blood from pregnancies with maternal preeclampsia due to untreated gestational diabetes mellitus

Original Article

The effects of acarbose on chemokine and cytokine production in human monocytic THP-1 cells

Original Article

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

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Studie zur HIFU bei Prostatakrebs lässt viele Fragen offen

22.01.2025
Prostatakarzinom
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Führt eine HIFU-Ablation beim Prostatakarzinom im Vergleich mit einer radikalen Prostatektomie zu ähnlichen onkologischen, aber besseren funktionalen Ergebnissen? Interimsdaten der französischen HIFI-Studie sind uneindeutig. In einem Kommentar zur Studie werden zumindest drei allgemeine Erkenntnisse herausgearbeitet.

Leitlinienkonformes Management thermischer Verletzungen

22.01.2025
Verbrennung
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Thermische Verletzungen gehören zu den schwerwiegendsten Traumen und hinterlassen oft langfristige körperliche und psychische Spuren. Die aktuelle S2k-Leitlinie „Behandlung thermischer Verletzungen im Kindesalter (Verbrennung, Verbrühung)“ bietet eine strukturierte Übersicht über das empfohlene Vorgehen.

Frühe Hyperoxie nach Reanimation schlecht für die Prognose?

22.01.2025
Kardiopulmonale Reanimation
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Kommt es sehr früh nach einer kardiopulmonalen Reanimation zu einem Zustand der Hyperoxie, ist dies bei Patientinnen und Patienten nach einem Herzstillstand mit schlechteren funktionellen Ergebnissen assoziiert. Das zeigt eine Sekundäranalyse der TTM-2-Studie.

Infektanfälligkeit in früher Kindheit: eine bleibende Last?

22.01.2025
Pädiatrische Infektiologie
Nachrichten

Wenn Kinder in den ersten Lebensjahren immer wieder Infekte durchmachen, lässt dies Schlüsse auf die Infektneigung in der weiteren Kindheit zu.

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

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Update Innere Medizin

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Springer Medizin

SOCS3 as a future target to treat metabolic disorders

Abstract

Weitere Artikel der Ausgabe 2/2019

Evaluation of growth and puberty in a child with a novel TBX19 gene mutation and review of the literature

A novel FGF8 mutation in a female patient with isolated congenital anosmia

Non-functioning pituitary macroadenoma: surgical outcomes, tumor regrowth, and alterations in pituitary function—3-year experience from the Iranian Pituitary Tumor Registry

Medical therapy for non-functioning pituitary tumors—a critical approach

Methylation profile of genes involved in inflammation, in the blood from pregnancies with maternal preeclampsia due to untreated gestational diabetes mellitus

The effects of acarbose on chemokine and cytokine production in human monocytic THP-1 cells

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Neu im Fachgebiet Innere Medizin

Studie zur HIFU bei Prostatakrebs lässt viele Fragen offen

Leitlinienkonformes Management thermischer Verletzungen

Frühe Hyperoxie nach Reanimation schlecht für die Prognose?

Infektanfälligkeit in früher Kindheit: eine bleibende Last?

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

Update Innere Medizin

Springer Medizin

Abstract

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