Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons

Journal of Neuroscience

Volumn 30, Issue 7, 2010, Pages 2472-2479

  Williams, Kevin W ^a   Margatho, Lisandra O ^a   Lee, Charlotte E ^a   Choi, Michelle ^a   Lee, Syann ^a   Scott, Michael M ^a   Elias, Carol F ^a   Elmquist, Joel K ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN; LEPTIN; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE;

ANIMAL EXPERIMENT; ARCUATE NUCLEUS; ARCUATE PROOPIOMELANOCORTIN CELL; ARTICLE; BRAIN MAPPING; CONTROLLED STUDY; ELECTROPHYSIOLOGY; ENZYME ACTIVATION; HYPOTHALAMUS; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NERVE CELL; NERVE CELL NETWORK; NONHUMAN; PATCH CLAMP; PRIORITY JOURNAL;

ACTION POTENTIALS; ANIMALS; GENE EXPRESSION REGULATION; GREEN FLUORESCENT PROTEINS; HYPOTHALAMUS; INSULIN; LEPTIN; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NEURONS; ONCOGENE PROTEINS V-FOS; PATCH-CLAMP TECHNIQUES; PRO-OPIOMELANOCORTIN; RECEPTOR, INSULIN; RNA, MESSENGER;

EID: 77249146406     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3118-09.2010     Document Type: Article

References (51)

1. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382:250-252.
2. Al-Qassab H, Smith MA, Irvine EE, Guillermet-Guibert J, Claret M, Choudhury AI, Selman C, Piipari K, Clements M, Lingard S, Chandarana K, Bell JD, Barsh GS, Smith AJ, Batterham RL, Ashford ML, Vanhaesebroeck B, Withers DJ (2009) Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab 10:343-354.
3. Baker RA, Herkenham M (1995) Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat. J Comp Neurol 358:518-530.
4. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr, Elmquist JK, Lowell BB (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983-991.
5. Bates SH, StearnsWH,Dundon TA, Schubert M, Tso AW, Wang Y, Banks AS, Lavery HJ, Haq AK, Maratos-Flier E, Neel BG, Schwartz MW, Myers MG Jr (2003) STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421:856-859.
6. Carvalheira JB, Torsoni MA, Ueno M, Amaral ME, Araújo EP, Velloso LA, Gontijo JA, Saad MJ (2005) Cross-talk between the insulin and leptin signaling systems in rat hypothalamus. Obes Res 13:48-57.
7. Cheung CC, Clifton DK, Steiner RA (1997) Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138:4489-4492.
8. Choudhury AI, Heffron H, Smith MA, Al-Qassab H, Xu AW, Selman C, Simmgen M, Clements M, Claret M, Maccoll G, Bedford DC, Hisadome K, Diakonov I, Moosajee V, Bell JD, Speakman JR, Batterham RL, Barsh GS, Ashford ML, Withers DJ (2005) The role of insulin receptor substrate 2 in hypothalamic and beta cell function. J Clin Invest 115:940-950.
9. Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, Clements M, Al-Qassab H, Heffron H, Xu AW, Speakman JR, Barsh GS, Viollet B, Vaulont S, Ashford ML, Carling D, Withers DJ (2007) AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest 117:2325-2336.
10. Cohen P, Zhao C, Cai X, Montez JM, Rohani SC, Feinstein P, Mombaerts P, Friedman JM (2001) Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 108:1113-1121.
11. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-484.
12. Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, Kenny CD, Christiansen LM, White RD, Edelstein EA, Coppari R, Balthasar N, Cowley MA, Chua S Jr, Elmquist JK, Lowell BB (2006) Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49:191-203.
13. Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, Kuhar MJ, Saper CB, Elmquist JK (1998) Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21:1375-1385.
14. Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS, Bjorbaek C, Flier JS, Saper CB, Elmquist JK (1999) Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23:775-786.
15. Elias CF, Kelly JF, Lee CE, Ahima RS, Drucker DJ, Saper CB, Elmquist JK (2000) Chemical characterization of leptin-activated neurons in the rat brain. J Comp Neurol 423:261-281.
16. Fukuda M, Jones JE, Olson D, Hill J, Lee CE, Gautron L, Choi M, Zigman JM, Lowell BB, Elmquist JK (2008) Monitoring FoxO1 localization in chemically identified neurons. J Neurosci 28:13640-13648.
17. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543-546.
18. Hill JW, Williams KW, Ye C, Luo J, Balthasar N, Coppari R, Cowley MA, Cantley LC, Lowell BB, Elmquist JK (2008) Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest 118:1796-1805.
19. Hill JW, Elias CF, Fukuda M, Williams KW, Berglund ED, Holland WL, Cho Y, Chuang J, Xu Y, Choi M, Lauzon D, Lee CE, Coppari R, Richardson JA, Zigman JM, Chua S, Scherer PE, Lowell BB, Br̈uning JC, Elmquist JK (2010) Direct insulin and leptin action in pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metabolism, in press.
20. Hoffman GE, Lyo D (2002) Anatomical markers of activity in neuroendocrine systems: are we all 'fos-ed out'? J Neuroendocrinol 14:259-268.
21. Hoffman GE, Smith MS, Verbalis JG (1993) c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. Front Neuroendocrinol 14:173-213.
22. Kennedy GC (1953) The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 140:578-596.
23. Könner AC, Janoschek R, Plum L, Jordan SD, Rother E, Ma X, Xu C, Enriori P, Hampel B, Barsh GS, Kahn CR, Cowley MA, Ashcroft FM, Brüning JC (2007) Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab 5:438-449.
24. Liu H, Kishi T, Roseberry AG, Cai X, Lee CE, Montez JM, Friedman JM, Elmquist JK (2003) Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter. J Neurosci 23:7143-7154.
25. Luckman SM, Dyball RE, Leng G (1994) Induction of c-fos expression in hypothalamic magnocellular neurons requires synaptic activation and not simply increased spike activity. J Neurosci 14:4825-4830.
26. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, et al (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155-1161.
27. Mirshamsi S, Laidlaw HA, Ning K, Anderson E, Burgess LA, Gray A, Sutherland C, Ashford ML (2004) Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation. BMC Neurosci 5:54.
28. Morrison CD, Morton GJ, Niswender KD, Gelling RW, Schwartz MW (2005) Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling. Am J Physiol Endocrinol Metab 289:E1051-1057.
29. Morton GJ, Gelling RW, Niswender KD, Morrison CD, Rhodes CJ, Schwartz MW (2005) Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab 2:411-420.
30. Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG Jr, Schwartz MW (2001) Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 413:794-795.
31. Obici S, Zhang BB, Karkanias G, Rossetti L (2002) Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 8:1376-1382.
32. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, Lowell BB (2007) Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449:228-232.
33. Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, et al. (2006) Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J Clin Invest 116:1886-1901.
34. Rahmouni K, Haynes WG, Morgan DA, Mark AL (2003) Intracellular mechanisms involved in leptin regulation of sympathetic outflow. Hypertension 41:763-767.
35. Ramadori G, Lee CE, Bookout AL, Lee S, Williams KW, Anderson J, Elmquist JK, Coppari R (2008) Brain SIRT1: anatomical distribution and regulation by energy availability. J Neurosci 28:9989-9996.
36. Sagar SM, Sharp FR, Curran T (1988) Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science 240:1328-1331.
37. Schwartz MW, Porte D Jr (2005) Diabetes, obesity, and the brain. Science 307:375-379.
38. Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML (2000) Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 3:757-758.
39. Spiegelman BM, Flier JS (2001) Obesity and the regulation of energy balance. Cell 104:531-543.
40. Swanson LW, Kuypers HG (1980) A direct projection from the ventrome-dial nucleus and retrochiasmatic area of the hypothalamus to the medulla and spinal cord of the rat. Neurosci Lett 17:307-312.
41. Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, Friedman JM (1996) Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 14:95-97.
42. Williams KW, Smith BN (2006) Rapid inhibition of neural excitability in the nucleus tractus solitarii by leptin: implications for ingestive behaviour. J Physiol 573:395-412.
43. WilliamsKW,ZsombokA, SmithBN (2007) Rapid inhibition of neurons in the dorsal motor nucleus of the vagus by leptin. Endocrinology 148:1868-1881.
44. Woods SC, Lotter EC, McKay LD, Porte D Jr (1979) Chronic intracerebro-ventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282:503-505.
45. Woods SC, Figlewicz Lattemann DP, Schwartz MW, Porte D Jr (1990) A re-assessment of the regulation of adiposity and appetite by the brain insulin system. Int J Obes 14 [Suppl 3]:69-73; discussion 74-66.
46. Woods SC, Chavez M, Park CR, Riedy C, Kaiyala K, Richardson RD, Figlewicz DP, Schwartz MW, Porte D Jr, Seeley RJ (1996) The evaluation of insulin as a metabolic signal influencing behavior via the brain. Neurosci Biobehav Rev 20:139-144.
47. Xu AW, Kaelin CB, Takeda K, Akira S, SchwartzMW,Barsh GS (2005) PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest 115:951-958.
48. Xu AW, Ste-Marie L, Kaelin CB, Barsh GS (2007) Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology 148:72-80.
49. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425-432.
50. Zhao AZ, Huan JN, Gupta S, Pal R, Sahu A (2002) A phosphatidylinositol 3-kinase phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding. Nat Neurosci 5:727-728.
51. Zheng H, Patterson LM, Phifer CB, Berthoud HR (2005) Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projections. Am J Physiol Regul Integr Comp Physiol 289:R247-R258.