Paraventricular hypothalamus mediates diurnal rhythm of metabolism.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 07 2020
30 07 2020
Historique:
received:
20
09
2019
accepted:
09
07
2020
entrez:
1
8
2020
pubmed:
1
8
2020
medline:
9
9
2020
Statut:
epublish
Résumé
Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening rhythmicity of GABAergic input to the PVH reduces diurnal rhythmicity in metabolism and causes obesity. Finally, BMAL1 deletion blunts PVH neuron responses to external stressors, an effect mimicked by HFD feeding. Thus, BMAL1-driven PVH neuron responsiveness in dynamic activity changes involving rhythmic GABAergic neurotransmission mediates diurnal rhythmicity in metabolism and is implicated in diet-induced obesity.
Identifiants
pubmed: 32732906
doi: 10.1038/s41467-020-17578-7
pii: 10.1038/s41467-020-17578-7
pmc: PMC7393104
doi:
Substances chimiques
ARNTL Transcription Factors
0
Bmal1 protein, mouse
0
Gabrg2 protein, mouse
0
Receptors, GABA-A
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3794Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK114037
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK113954
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD083092
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114279
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS108091
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH117089
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117281
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103555
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109934
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101379
Pays : United States
Références
Bechtold, D. A. & Loudon, A. S. Hypothalamic clocks and rhythms in feeding behaviour. Trends Neurosci. 36, 74–82 (2013).
pubmed: 23333345
Mohawk, J. A., Green, C. B. & Takahashi, J. S. Central and peripheral circadian clocks in mammals. Annu. Rev. Neurosci. 35, 445–462 (2012).
pubmed: 22483041
pmcid: 3710582
Colwell, C. S. Linking neural activity and molecular oscillations in the SCN. Nat. Rev. Neurosci. 12, 553–569 (2011).
pubmed: 21886186
pmcid: 4356239
Izumo, M. et al. Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant. eLife https://doi.org/10.7554/eLife.04617 (2014).
Satinoff, E. & Prosser, R. A. Suprachiasmatic nuclear lesions eliminate circadian rhythms of drinking and activity, but not of body temperature, in male rats. J. Biol. Rhythms 3, 1–22 (1988).
pubmed: 2979628
Turek, F. W. et al. Obesity and metabolic syndrome in circadian clock mutant mice. Science 308, 1043–1045 (2005).
pubmed: 15845877
pmcid: 3764501
Yang, S. et al. The role of mPer2 clock gene in glucocorticoid and feeding rhythms. Endocrinology 150, 2153–2160 (2009).
pubmed: 19179447
pmcid: 2671901
Gatfield, D. & Schibler, U. Circadian glucose homeostasis requires compensatory interference between brain and liver clocks. Proc. Natl Acad. Sci. USA 105, 14753–14754 (2008).
pubmed: 18812506
Kohsaka, A. et al. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 6, 414–421 (2007).
pubmed: 17983587
Hood, S. & Amir, S. The aging clock: circadian rhythms and later life. J. Clin. Invest. 127, 437–446 (2017).
pubmed: 28145903
pmcid: 5272178
Hatori, M. et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 15, 848–860 (2012).
pubmed: 22608008
pmcid: 3491655
Chaix, A., Zarrinpar, A., Miu, P. & Panda, S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 20, 991–1005 (2014).
pubmed: 25470547
pmcid: 4255155
van der Klaauw, A. A. & Farooqi, I. S. The hunger genes: pathways to obesity. Cell 161, 119–132 (2015).
pubmed: 25815990
Sandoval, D., Cota, D. & Seeley, R. J. The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. Annu. Rev. Physiol. 70, 513–535 (2008).
pubmed: 17988209
Sutton, A. K., Myers, M. G. Jr. & Olson, D. P. The role of PVH circuits in leptin action and energy balance. Annu. Rev. Physiol. 78, 207–221 (2016).
pubmed: 26863324
pmcid: 5087283
Atasoy, D., Betley, J. N., Su, H. H. & Sternson, S. M. Deconstruction of a neural circuit for hunger. Nature 488, 172–177 (2012).
pubmed: 22801496
pmcid: 3416931
Wu, Z. et al. GABAergic projections from lateral hypothalamus to paraventricular hypothalamic nucleus promote feeding. J. Neurosci. 35, 3312–3318 (2015).
pubmed: 25716832
pmcid: 4339348
Mangieri, L. R. et al. A neural basis for antagonistic control of feeding and compulsive behaviors. Nat. Commun. 9, 52 (2018).
pubmed: 29302029
pmcid: 5754347
Liu, T. et al. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 73, 511–522 (2012).
pubmed: 22325203
pmcid: 3278709
Kim, E. R. et al. Hypothalamic non-AgRP, non-POMC GABAergic neurons are required for postweaning geeding and NPY hyperphagia. J. Neurosci. 35, 10440–10450 (2015).
pubmed: 26203139
pmcid: 4510285
Zhang, X. & van den Pol, A. N. Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis. Nat. Neurosci. 19, 1341–1347 (2016).
pubmed: 27548245
pmcid: 6402046
Vong, L. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142–154 (2011).
pubmed: 21745644
pmcid: 3134797
Li, A. J. et al. Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 302, R1313–R1326 (2012).
pubmed: 22492818
pmcid: 3378345
Girotti, M., Weinberg, M. S. & Spencer, R. L. Diurnal expression of functional and clock-related genes throughout the rat HPA axis: system-wide shifts in response to a restricted feeding schedule. Am. J. Physiol. Endocrinol. Metab. 296, E888–E897 (2009).
pubmed: 19190255
pmcid: 2670633
Wulff, P. et al. From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nat. Neurosci. 10, 923–929 (2007).
pubmed: 17572671
pmcid: 2092503
Cardinali, D. P. & Golombek, D. A. The rhythmic GABAergic system. Neurochem. Res. 23, 607–614 (1998).
pubmed: 9566598
Naum, O. G., Fernanda Rubio, M. & Golombek, D. A. Rhythmic variation in gamma-aminobutyric acid(A)-receptor subunit composition in the circadian system and median eminence of Syrian hamsters. Neurosci. Lett. 310, 178–182 (2001).
Tousson, E. & Meissl, H. Suprachiasmatic nuclei grafts restore the circadian rhythm in the paraventricular nucleus of the hypothalamus. J. Neurosci. 24, 2983–2988 (2004).
pubmed: 15044537
pmcid: 6729855
Kim, J. et al. Rapid, biphasic CRF neuronal responses encode positive and negative valence. Nat. Neurosci. 22, 576–585 (2019).
pubmed: 30833699
pmcid: 6668342
Xue, M., Atallah, B. V. & Scanziani, M. Equalizing excitation-inhibition ratios across visual cortical neurons. Nature 511, 596–600 (2014).
pubmed: 25043046
pmcid: 4117808
Sim, S., Antolin, S., Lin, C. W., Lin, Y. & Lois, C. Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4. J. Neurosci. 33, 7928–7940 (2013).
pubmed: 23637184
pmcid: 3853377
Patel, J. M. et al. Sensory perception drives food avoidance through excitatory basal forebrain circuits. eLife https://doi.org/10.7554/eLife.44548 (2019).
Melnick, I., Pronchuk, N., Cowley, M. A., Grove, K. L. & Colmers, W. F. Developmental switch in neuropeptide Y and melanocortin effects in the paraventricular nucleus of the hypothalamus. Neuron 56, 1103–1115 (2007).
pubmed: 18093530
Mehta, A., Prabhakar, M., Kumar, P., Deshmukh, R. & Sharma, P. L. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur. J. Pharmacol. 698, 6–18 (2013).
pubmed: 23123057
Ulrich-Lai, Y. M. & Herman, J. P. Neural regulation of endocrine and autonomic stress responses. Nat. Rev. Neurosci. 10, 397–409 (2009).
pubmed: 19469025
pmcid: 4240627
Panda, S. Circadian physiology of metabolism. Science 354, 1008–1015 (2016).
pubmed: 27885007
pmcid: 7261592
Krashes, M. J. et al. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature 507, 238–242 (2014).
pubmed: 24487620
pmcid: 3955843
Stachniak, T. J., Ghosh, A. & Sternson, S. M. Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus–>midbrain pathway for feeding behavior. Neuron 82, 797–808 (2014).
pubmed: 24768300
pmcid: 4306349
Garfield, A. S. et al. A neural basis for melanocortin-4 receptor-regulated appetite. Nat. Neurosci. 18, 863–871 (2015).
pubmed: 25915476
pmcid: 4446192
Sutton, A. K. et al. Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus. J. Neurosci. 34, 15306–15318 (2014).
pubmed: 25392498
pmcid: 4228133
Zhan, C. et al. Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. J. Neurosci. 33, 3624–3632 (2013).
pubmed: 23426689
pmcid: 6619547
Xi, D., Gandhi, N., Lai, M. & Kublaoui, B. M. Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. PLoS ONE 7, e36453 (2012).
pubmed: 22558467
pmcid: 3338647
Kalsbeek, A. et al. Circadian control of the daily plasma glucose rhythm: an interplay of GABA and glutamate. PLoS ONE 3, e3194 (2008).
pubmed: 18791643
pmcid: 2527681
van Dijk, G. & Strubbe, J. H. Time-dependent effects of neuropeptide Y infusion in the paraventricular hypothalamus on ingestive and associated behaviors in rats. Physiol. Behav. 79, 575–580 (2003).
pubmed: 12954397
Chiesa, J. J., Cambras, T., Carpentieri, A. R. & Diez-Noguera, A. Arrhythmic rats after SCN lesions and constant light differ in short time scale regulation of locomotor activity. J. Biol. Rhythms 25, 37–46 (2010).
pubmed: 20075299
Li, M. M. et al. The paraventricular hypothalamus regulates satiety and prevents obesity via two genetically distinct circuits. Neuron 102, 653–667 e656 (2019).
pubmed: 30879785
pmcid: 6508999
Balthasar, N. et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493–505 (2005).
pubmed: 16269339
Xu, Y. et al. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab. 18, 860–870 (2013).
pubmed: 24315371
Vella, K. R. et al. NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways. Cell Metab. 14, 780–790 (2011).
pubmed: 22100407
pmcid: 3261758
Herman, J. P. & Tasker, J. G. Paraventricular hypothalamic mechanisms of chronic stress adaptation. Front. Endocrinol. (Lausanne) 7, 137 (2016).
Swanson, L. W. & Sawchenko, P. E. Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms. Neuroendocrinology 31, 410–417 (1980).
pubmed: 6109264
Wu, Y. E. et al. Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus. Proc. Natl Acad. Sci. USA 115, E9469–E9478 (2018).
pubmed: 30228120
Iremonger, K. J. & Bains, J. S. Dynamic synapses in the hypothalamic-neurohypophyseal system. Prog. Brain Res. 170, 119–128 (2008).
pubmed: 18655877
Li, C. et al. Defined paraventricular hypothalamic populations exhibit differential responses to food contingent on caloric state. Cell Metab, https://doi.org/10.1016/j.cmet.2018.10.016 (2018).
Li, D. P. & Pan, H. L. Glutamatergic regulation of hypothalamic presympathetic neurons in hypertension. Curr. Hypertens. Rep. 19, 78 (2017).
pubmed: 28929331
de Lartigue, G. Role of the vagus nerve in the development and treatment of diet-induced obesity. J. Physiol. 594, 5791–5815 (2016).
pubmed: 26959077
pmcid: 5063945
Horvath, T. L. et al. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc. Natl Acad. Sci. USA 107, 14875–14880 (2010).
pubmed: 20679202
Mazier, W. et al. mTORC1 and CB1 receptor signaling regulate excitatory glutamatergic inputs onto the hypothalamic paraventricular nucleus in response to energy availability. Mol. Metab. 28, 151–159 (2019).
pubmed: 31420305
pmcid: 6822143
Kong, D. et al. GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure. Cell 151, 645–657 (2012).
pubmed: 23101631
pmcid: 3500616
Liu, T., Wang, Q., Berglund, E. D. & Tong, Q. Action of neurotransmitter: a key to unlock the AgRP neuron feeding circuit. Front. Neurosci. 6, 200 (2012).
pubmed: 23346045
Lorez, M., Benke, D., Luscher, B., Mohler, H. & Benson, J. A. Single-channel properties of neuronal GABAA receptors from mice lacking the 2 subunit. J. Physiol. 527(Pt 1), 11–31 (2000).
pubmed: 10944167
pmcid: 2270058
Luquet, S., Perez, F. A., Hnasko, T. S. & Palmiter, R. D. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310, 683–685 (2005).
pubmed: 16254186
Storch, K. F. et al. Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information. Cell 130, 730–741 (2007).
pubmed: 17719549
pmcid: 2040024
Chen, T. W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
pubmed: 23868258
pmcid: 3777791