Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons

Nature Communications

Volumn 6, Issue , 2015, Pages

  Lee, Dong Kun ^a   Jeong, Jae Hoon ^a   Chun, Sung Kun ^a   Chua, Streamson ^a   Jo, Young Hwan ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; CALCIUM ION; GLUCOSE; GLUTAMIC ACID; JANUS KINASE 2; LEPTIN; MELANOCORTIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROOPIOMELANOCORTIN; TRANSIENT RECEPTOR POTENTIAL CHANNEL C; 4 AMINOBUTYRIC ACID RECEPTOR; GLUCOSE BLOOD LEVEL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LEPTIN RECEPTOR; LEPTIN RECEPTOR, MOUSE; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; METABOTROPIC RECEPTOR; PHOSPHOLIPASE C;

FAT; GENE EXPRESSION; GLUCOSE; HOMEOSTASIS; HORMONE; INHIBITION; NEUROLOGY; SIGNALING;

4 AMINOBUTYRIC ACID RELEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY COMPOSITION; CALCIUM CELL LEVEL; CONTROLLED STUDY; ENERGY BALANCE; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FAT INTAKE; FEMALE; GABAERGIC TRANSMISSION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; HYPERPOLARIZATION; MALE; MOUSE; NEGATIVE FEEDBACK; NERVE CELL; NERVE CELL NETWORK; NEUROTRANSMITTER RELEASE; NONHUMAN; POMC NEURON; POSTSYNAPTIC POTENTIAL; PRESYNAPTIC INHIBITION; PRESYNAPTIC POTENTIAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; SYNAPSE; SYNAPTOSOME; UPREGULATION; ZONA INCERTA; ANIMAL; BRAIN; DRUG EFFECTS; GENETICS; HOMEOSTASIS; LIPID DIET; METABOLISM; NERVE CELL INHIBITION; NERVE ENDING; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; BLOOD GLUCOSE; BRAIN; DIET, HIGH-FAT; GABAERGIC NEURONS; GLUCOSE; HOMEOSTASIS; JANUS KINASE 2; LEPTIN; MICE; MICE, TRANSGENIC; NEURAL INHIBITION; NEURONS; PHOSPHATIDYLINOSITOL 3-KINASES; PRESYNAPTIC TERMINALS; PRO-OPIOMELANOCORTIN; RECEPTOR, MELANOCORTIN, TYPE 3; RECEPTOR, MELANOCORTIN, TYPE 4; RECEPTORS, LEPTIN; RECEPTORS, METABOTROPIC GLUTAMATE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SYNAPSES; TRPC CATION CHANNELS; TYPE C PHOSPHOLIPASES;

EID: 84925834932     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms7618     Document Type: Article

References (53)

1. Flier, J. S. Obesity wars: molecular progress confronts an expanding epidemic. Cell 116, 337-350 (2004).
2. Friedman, J. M. Obesity in the new millennium. Nature 404, 632-634 (2000).
3. Patterson, C. M., Leshan, R. L., Jones, J. C. & Myers, Jr. M. G. Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells. Brain Res. 1378, 18-28 (2011).
4. Elmquist, J. K., Bjorbaek, C., Ahima, R. S., Flier, J. S. & Saper, C. B. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395, 535-547 (1998).
5. Cone, R. D. Anatomy and regulation of the central melanocortin system. Nat. Neurosci. 8, 571-578 (2005).
6. Belgardt, B. F., Okamura, T. & Bruning, J. C. Hormone and glucose signalling in POMC and AgRP neurons. J. Physiol. 587, 5305-5314 (2009).
7. Yaswen, L., Diehl, N., Brennan, M. B. & Hochgeschwender, U. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat. Med. 5, 1066-1070 (1999).
8. Challis, B. G. et al. Mice lacking pro-opiomelanocortin are sensitive to highfat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). Proc. Natl Acad. Sci. USA 101, 4695-4700 (2004).
9. Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131-141 (1997).
10. Butler, A. A. et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141, 3518-3521 (2000).
11. Krude, H. et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 19, 155-157 (1998).
12. Jackson, R. S. et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat. Genet. 16, 303-306 (1997).
13. Yeo, G. S. et al. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 20, 111-112 (1998).
14. Vaisse, C., Clement, K., Guy-Grand, B. & Froguel, P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113-114 (1998).
15. Qiu, J., Fang, Y., Ronnekleiv, O. K. & Kelly, M. J. Leptin excites proopiomelanocortin neurons via activation of TRPC channels. J. Neurosci. 30, 1560-1565 (2010).
16. Plum, L. et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J. Clin. Invest. 116, 1886-1901 (2006).
17. Hill, J. W. et al. Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J. Clin. Invest. 118, 1796-1805 (2008).
18. Al-Qassab, H. et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab. 10, 343-354 (2009).
19. Ernst, M. B. et al. Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity. J. Neurosci. 29, 11582-11593 (2009).
20. Reed, A. S. et al. Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes 59, 894-906 (2010).
21. Bates, S. H. et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421, 856-859 (2003).
22. Minokoshi, Y. et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428, 569-574 (2004).
23. Dagon, Y. et al. p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake. Cell Metab. 16, 104-112 (2012).
24. Martin, T. L. et al. Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle. J. Biol. Chem. 281, 18933-18941 (2006).
25. Claret, M. et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J. Clin. Invest. 117, 2325-2336 (2007).
26. Parton, L. E. et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449, 228-232 (2007).
27. Enriori, P. J. et al. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab. 5, 181-194 (2007).
28. Cowley, M. A. et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411, 480-484 (2001).
29. Vong, L. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142-154 (2011).
30. Ha, S. et al. Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons. PLoS ONE 8, e77622 (2013).
31. Balthasar, N. et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42, 983-991 (2004).
32. Chun, S. K. & Jo, Y. H. Loss of leptin receptors on hypothalamic POMC neurons alters synaptic inhibition. J. Neurophysiol. 104, 2321-2328 (2010).
33. Knight, Z. A. et al. Molecular profiling of activated neurons by phosphorylated ribosome capture. Cell 151, 1126-1137 (2012).
34. Munzberg, H. et al. Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling. J. Neurosci. 27, 69-74 (2007).
35. Munsch, T., Freichel, M., Flockerzi, V. & Pape, H. C. Contribution of transient receptor potential channels to the control of GABA release from dendrites. Proc. Natl Acad. Sci. USA 100, 16065-16070 (2003).
36. Qiu, J. et al. Insulin excites anorexigenic proopiomelanocortin neurons via activation of canonical transient receptor potential channels. Cell Metab. 19, 682-693 (2014).
37. Yang, Y., Atasoy, D., Su, H. H. & Sternson, S. M. Hunger states switch a flipflop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell 146, 992-1003 (2011).
38. Mirshamsi, S. et al. Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation. BMC Neurosci. 5, 54 (2004).
39. Smith, M. A. et al. Melanocortins and agouti-related protein modulate the excitability of two arcuate nucleus neuron populations by alteration of resting potassium conductances. J. Physiol. 578, 425-438 (2007).
40. Pennock, R. L. & Hentges, S. T. Differential expression and sensitivity of presynaptic and postsynaptic opioid receptors regulating hypothalamic proopiomelanocortin neurons. J. Neurosci. 31, 281-288 (2011).
41. Yee, C. L., Wang, Y., Anderson, S., Ekker, M. & Rubenstein, J. L. Arcuate nucleus expression of NKX2.1 and DLX and lineages expressing these transcription factors in neuropeptide Y(+), proopiomelanocortin(+), and tyrosine hydroxylase(+) neurons in neonatal and adult mice. J. Comp. Neurol. 517, 37-50 (2009).
42. Hentges, S. T., Otero-Corchon, V., Pennock, R. L., King, C. M. & Low, M. J. Proopiomelanocortin expression in both GABA and glutamate neurons. J. Neurosci. 29, 13684-13690 (2009).
43. Collin, M. et al. Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight. Eur. J. Neurosci. 18, 1265-1278 (2003).
44. Bodnar, R. J. Endogenous opioids and feeding behavior: a 30-year historical perspective. Peptides 25, 697-725 (2004).
45. Glass, M. J., Billington, C. J. & Levine, A. S. Opioids and food intake: distributed functional neural pathways? Neuropeptides 33, 360-368 (1999).
46. Kalra, S. P. & Horvath, T. L. Neuroendocrine interactions between galanin, opioids, and neuropeptide Y in the control of reproduction and appetite. Ann. N. Y. Acad. Sci. 863, 236-240 (1998).
47. Aponte, Y., Atasoy, D. & Sternson, S. M. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat. Neurosci. 14, 351-355 (2011).
48. Williams, K. W. et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J. Neurosci. 30, 2472-2479 (2010).
49. Xu, A. W., Ste-Marie, L., Kaelin, C. B. & Barsh, G. S. 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 (2007).
50. Strubing, C., Krapivinsky, G., Krapivinsky, L. & Clapham, D. E. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29, 645-655 (2001).
51. Lin, S., Thomas, T. C., Storlien, L. H. & Huang, X. F. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int. J. Obes. Relat. Metab. Disord. 24, 639-646 (2000).
52. Munzberg, H., Flier, J. S. & Bjorbaek, C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 145, 4880-4889 (2004).
53. El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjorbaek, C. & Flier, J. S. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J. Clin. Invest. 105, 1827-1832 (2000).