Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions

Cell Reports

Volumn 16, Issue 11, 2016, Pages 3003-3015

  Kaneko, Kentaro ^a   Xu, Pingwen ^a   Cordonier, Elizabeth L ^a   Chen, Siyu S ^a   Ng, Amy ^a   Xu, Yong ^a   Morozov, Alexei ^b,c   Fukuda, Makoto ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^c VIRGINIA TECH CARILION SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LEPTIN; RAP1 PROTEIN; BENZENE DERIVATIVE; ESI-05; GLUCOSE; RAP1 PROTEIN, MOUSE; SULFONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL LOSS; CONTROLLED STUDY; DISEASE ASSOCIATION; ENDOPLASMIC RETICULUM STRESS; ENERGY BALANCE; GLUCOSE HOMEOSTASIS; INSULIN RESISTANCE; LIPID DIET; METABOLIC DISORDER; METABOLIC REGULATION; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; WEIGHT REDUCTION; ANIMAL; C57BL MOUSE; CENTRAL NERVOUS SYSTEM; DEFICIENCY; DRUG EFFECTS; ENERGY METABOLISM; FEMALE; HOMEOSTASIS; METABOLISM; NERVE CELL; OVERNUTRITION; PATHOLOGY; REPRODUCIBILITY;

ANIMALS; BENZENE DERIVATIVES; CENTRAL NERVOUS SYSTEM; DIET, HIGH-FAT; ENDOPLASMIC RETICULUM STRESS; ENERGY METABOLISM; FEMALE; GLUCOSE; HOMEOSTASIS; INSULIN RESISTANCE; LEPTIN; MICE, INBRED C57BL; NEURONS; OBESITY; OVERNUTRITION; RAP1 GTP-BINDING PROTEINS; REPRODUCIBILITY OF RESULTS; SULFONES;

EID: 84994807642     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.08.039     Document Type: Article

References (60)

1. Bates, S.H., Stearns, W.H., Dundon, T.A., Schubert, M., Tso, A.W., Wang, Y., Banks, A.S., Lavery, H.J., Haq, A.K., Maratos-Flier, E., et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421 (2003), 856-859.
2. Bence, K.K., Delibegovic, M., Xue, B., Gorgun, C.Z., Hotamisligil, G.S., Neel, B.G., Kahn, B.B., Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat. Med. 12 (2006), 917-924.
3. Bjørbaek, C., Elmquist, J.K., Frantz, J.D., Shoelson, S.E., Flier, J.S., Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol. Cell 1 (1998), 619-625.
4. Cakir, I., Cyr, N.E., Perello, M., Litvinov, B.P., Romero, A., Stuart, R.C., Nillni, E.A., Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing. J. Biol. Chem. 288 (2013), 17675-17688.
5. Coll, A.P., Farooqi, I.S., O'Rahilly, S., The hormonal control of food intake. Cell 129 (2007), 251-262.
6. Cook, W.S., Unger, R.H., Protein tyrosine phosphatase 1B: a potential leptin resistance factor of obesity. Dev. Cell 2 (2002), 385-387.
7. de Rooij, J., Zwartkruis, F.J., Verheijen, M.H., Cool, R.H., Nijman, S.M., Wittinghofer, A., Bos, J.L., Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396 (1998), 474-477.
8. De Souza, C.T., Araujo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Saad, M.J., Velloso, L.A., Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146 (2005), 4192-4199.
9. Dietrich, M.O., Horvath, T.L., Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends Neurosci. 36 (2013), 65-73.
10. Frederich, R.C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B.B., Flier, J.S., Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat. Med. 1 (1995), 1311-1314.
11. Fukuda, M., Williams, K.W., Gautron, L., Elmquist, J.K., Induction of leptin resistance by activation of cAMP-Epac signaling. Cell Metab. 13 (2011), 331-339.
12. Gao, Q., Wolfgang, M.J., Neschen, S., Morino, K., Horvath, T.L., Shulman, G.I., Fu, X.Y., Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc. Natl. Acad. Sci. USA 101 (2004), 4661-4666.
13. Gloerich, M., Bos, J.L., Regulating Rap small G-proteins in time and space. Trends Cell Biol. 21 (2011), 615-623.
14. Halaas, J.L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D.A., Friedman, J.M., Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc. Natl. Acad. Sci. USA 94 (1997), 8878-8883.
15. Hosoi, T., Sasaki, M., Miyahara, T., Hashimoto, C., Matsuo, S., Yoshii, M., Ozawa, K., Endoplasmic reticulum stress induces leptin resistance. Mol. Pharmacol. 74 (2008), 1610-1619.
16. Hosoi, T., Yamaguchi, R., Noji, K., Matsuo, S., Baba, S., Toyoda, K., Suezawa, T., Kayano, T., Tanaka, S., Ozawa, K., Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress. EMBO Mol. Med. 6 (2014), 335-346.
17. Howard, J.K., Cave, B.J., Oksanen, L.J., Tzameli, I., Bjørbaek, C., Flier, J.S., Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat. Med. 10 (2004), 734-738.
18. Kälin, S., Heppner, F.L., Bechmann, I., Prinz, M., Tschöp, M.H., Yi, C.X., Hypothalamic innate immune reaction in obesity. Nat Rev Endocrinol 11 (2015), 339-351.
19. Kai, A.K., Lam, A.K., Chen, Y., Tai, A.C., Zhang, X., Lai, A.K., Yeung, P.K., Tam, S., Wang, J., Lam, K.S., et al. Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome. FASEB J. 27 (2013), 4122-4135.
20. Kawasaki, H., Springett, G.M., Mochizuki, N., Toki, S., Nakaya, M., Matsuda, M., Housman, D.E., Graybiel, A.M., A family of cAMP-binding proteins that directly activate Rap1. Science 282 (1998), 2275-2279.
21. Kim, S., Mizoguchi, A., Kikuchi, A., Takai, Y., Tissue and subcellular distributions of the smg-21/rap1/Krev-1 proteins which are partly distinct from those of c-ras p21s. Mol. Cell. Biol. 10 (1990), 2645-2652.
22. Kleinridders, A., Schenten, D., Könner, A.C., Belgardt, B.F., Mauer, J., Okamura, T., Wunderlich, F.T., Medzhitov, R., Brüning, J.C., MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab. 10 (2009), 249-259.
23. Könner, A.C., Brüning, J.C., Selective insulin and leptin resistance in metabolic disorders. Cell Metab. 16 (2012), 144-152.
24. Liu, X.B., Murray, K.D., Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: location, location, location. Epilepsia 53:Suppl 1 (2012), 45-52.
25. Liu, J., Lee, J., Salazar Hernandez, M.A., Mazitschek, R., Ozcan, U., Treatment of obesity with celastrol. Cell 161 (2015), 999-1011.
26. Locke, A.E., Kahali, B., Berndt, S.I., Justice, A.E., Pers, T.H., Day, F.R., Powell, C., Vedantam, S., Buchkovich, M.L., Yang, J., et al. LifeLines Cohort Study ADIPOGen Consortium AGEN-BMI Working Group CARDIOGRAMplusC4D Consortium CKDGen Consortium GLGC ICBP MAGIC Investigators MuTHER Consortium MIGen Consortium PAGE Consortium ReproGen Consortium GENIE Consortium, International Endogene Consortium. Genetic studies of body mass index yield new insights for obesity biology. Nature 518 (2015), 197-206.
27. Loh, K., Fukushima, A., Zhang, X., Galic, S., Briggs, D., Enriori, P.J., Simonds, S., Wiede, F., Reichenbach, A., Hauser, C., et al. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance. Cell Metab. 14 (2011), 684-699.
28. Manning, B.D., Cantley, L.C., AKT/PKB signaling: navigating downstream. Cell 129 (2007), 1261-1274.
29. Metlakunta, A.S., Sahu, M., Sahu, A., Hypothalamic phosphatidylinositol 3-kinase pathway of leptin signaling is impaired during the development of diet-induced obesity in FVB/N mice. Endocrinology 149 (2008), 1121-1128.
30. Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D.E., Tsukumo, D.M., Anhe, G., Amaral, M.E., Takahashi, H.K., et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J. Neurosci. 29 (2009), 359-370.
31. Minichiello, L., Korte, M., Wolfer, D., Kühn, R., Unsicker, K., Cestari, V., Rossi-Arnaud, C., Lipp, H.P., Bonhoeffer, T., Klein, R., Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24 (1999), 401-414.
32. Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K.R., Yasukawa, H., Yoshimura, A., Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat. Med. 10 (2004), 739-743.
33. Morton, G.J., Cummings, D.E., Baskin, D.G., Barsh, G.S., Schwartz, M.W., Central nervous system control of food intake and body weight. Nature 443 (2006), 289-295.
34. Myers, M.G. Jr., Olson, D.P., Central nervous system control of metabolism. Nature 491 (2012), 357-363.
35. Myers, M.G. Jr., Leibel, R.L., Seeley, R.J., Schwartz, M.W., Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol. Metab. 21 (2010), 643-651.
36. Neves, S.R., Ram, P.T., Iyengar, R., G protein pathways. Science 296 (2002), 1636-1639.
37. Ozcan, U., Yilmaz, E., Ozcan, L., Furuhashi, M., Vaillancourt, E., Smith, R.O., Görgün, C.Z., Hotamisligil, G.S., Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313 (2006), 1137-1140.
38. Ozcan, L., Ergin, A.S., Lu, A., Chung, J., Sarkar, S., Nie, D., Myers, M.G. Jr., Ozcan, U., Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 9 (2009), 35-51.
39. Pan, B.X., Vautier, F., Ito, W., Bolshakov, V.Y., Morozov, A., Enhanced cortico-amygdala efficacy and suppressed fear in absence of Rap1. J. Neurosci. 28 (2008), 2089-2098.
40. Pedroso, J.A., Buonfiglio, D.C., Cardinali, L.I., Furigo, I.C., Ramos-Lobo, A.M., Tirapegui, J., Elias, C.F., Donato, J. Jr., Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity. Mol. Metab. 3 (2014), 608-618.
41. Rahmouni, K., Haynes, W.G., Morgan, D.A., Mark, A.L., Selective resistance to central neural administration of leptin in agouti obese mice. Hypertension 39 (2002), 486-490.
42. Reed, A.S., Unger, E.K., Olofsson, L.E., Piper, M.L., Myers, M.G. Jr., Xu, A.W., Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes 59 (2010), 894-906.
43. Rehmann, H., Epac-inhibitors: facts and artefacts. Sci. Rep., 3, 2013, 3032.
44. Ryan, K.K., Woods, S.C., Seeley, R.J., Central nervous system mechanisms linking the consumption of palatable high-fat diets to the defense of greater adiposity. Cell Metab. 15 (2012), 137-149.
45. Sands, W.A., Woolson, H.D., Milne, G.R., Rutherford, C., Palmer, T.M., Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol. Cell. Biol. 26 (2006), 6333-6346.
46. Schneeberger, M., Dietrich, M.O., Sebastián, D., Imbernón, M., Castaño, C., Garcia, A., Esteban, Y., Gonzalez-Franquesa, A., Rodríguez, I.C., Bortolozzi, A., et al. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 155 (2013), 172-187.
47. Schwartz, M.W., Peskind, E., Raskind, M., Boyko, E.J., Porte, D. Jr., Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat. Med. 2 (1996), 589-593.
48. Song, W.J., Mondal, P., Li, Y., Lee, S.E., Hussain, M.A., Pancreatic β-cell response to increased metabolic demand and to pharmacologic secretagogues requires EPAC2A. Diabetes 62 (2013), 2796-2807.
49. Spilker, C., Kreutz, M.R., RapGAPs in brain: multipurpose players in neuronal Rap signalling. Eur. J. Neurosci. 32 (2010), 1-9.
50. Tsalkova, T., Mei, F.C., Li, S., Chepurny, O.G., Leech, C.A., Liu, T., Holz, G.G., Woods, V.L. Jr., Cheng, X., Isoform-specific antagonists of exchange proteins directly activated by cAMP. Proc. Natl. Acad. Sci. USA 109 (2012), 18613-18618.
51. Vaisse, C., Halaas, J.L., Horvath, C.M., Darnell, J.E. Jr., Stoffel, M., Friedman, J.M., Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat. Genet. 14 (1996), 95-97.
52. Walter, P., Ron, D., The unfolded protein response: from stress pathway to homeostatic regulation. Science 334 (2011), 1081-1086.
53. Williams, K.W., Liu, T., Kong, X., Fukuda, M., Deng, Y., Berglund, E.D., Deng, Z., Gao, Y., Liu, T., Sohn, J.W., et al. Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis. Cell Metab. 20 (2014), 471-482.
54. Won, J.C., Jang, P.G., Namkoong, C., Koh, E.H., Kim, S.K., Park, J.Y., Lee, K.U., Kim, M.S., Central administration of an endoplasmic reticulum stress inducer inhibits the anorexigenic effects of leptin and insulin. Obesity (Silver Spring) 17 (2009), 1861-1865.
55. Yan, J., Mei, F.C., Cheng, H., Lao, D.H., Hu, Y., Wei, J., Patrikeev, I., Hao, D., Stutz, S.J., Dineley, K.T., et al. Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1. Mol. Cell. Biol. 33 (2013), 918-926.
56. Zabolotny, J.M., Bence-Hanulec, K.K., Stricker-Krongrad, A., Haj, F., Wang, Y., Minokoshi, Y., Kim, Y.B., Elmquist, J.K., Tartaglia, L.A., Kahn, B.B., Neel, B.G., PTP1B regulates leptin signal transduction in vivo. Dev. Cell 2 (2002), 489-495.
57. Zhang, E.E., Chapeau, E., Hagihara, K., Feng, G.S., Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc. Natl. Acad. Sci. USA 101 (2004), 16064-16069.
58. Zhang, R., Dhillon, H., Yin, H., Yoshimura, A., Lowell, B.B., Maratos-Flier, E., Flier, J.S., Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology 149 (2008), 5654-5661.
59. Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., Cai, D., Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135 (2008), 61-73.
60. Zhang, C.L., Katoh, M., Shibasaki, T., Minami, K., Sunaga, Y., Takahashi, H., Yokoi, N., Iwasaki, M., Miki, T., Seino, S., The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. Science 325 (2009), 607-610.