Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.
Animals
Energy Metabolism
/ genetics
Hypothalamus
/ metabolism
Body Composition
Mice
Homeostasis
Eating
/ genetics
Mice, Knockout
Homeodomain Proteins
/ genetics
Diet, High-Fat
Transcription Factors
/ metabolism
Male
Mice, Inbred C57BL
Neurons
/ metabolism
Pro-Opiomelanocortin
/ metabolism
Insulin Resistance
/ genetics
Arcuate Nucleus of Hypothalamus
/ metabolism
Alx3
Body mass composition
Energy homeostasis
MC3R
Metabolic partitioning
Proopiomelanocortin
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
10
07
2023
accepted:
27
07
2024
revised:
03
07
2024
medline:
12
8
2024
pubmed:
12
8
2024
entrez:
11
8
2024
Statut:
epublish
Résumé
The coordination of food intake, energy storage, and expenditure involves complex interactions between hypothalamic neurons and peripheral tissues including pancreatic islets, adipocytes, muscle, and liver. Previous research shows that deficiency of the transcription factor Alx3 alters pancreatic islet-dependent glucose homeostasis. In this study we carried out a comprehensive assessment of metabolic alterations in Alx3 deficiency. We report that Alx3-deficient mice exhibit decreased food intake without changes in body weight, along with reduced energy expenditure and altered respiratory exchange ratio. Magnetic resonance imaging reveals increased adiposity and decreased muscle mass, which was associated with markers of motor and sympathetic denervation. By contrast, Alx3-deficient mice on a high-fat diet show attenuated weight gain and improved insulin sensitivity, compared to control mice. Gene expression analysis demonstrates altered lipogenic and lipolytic gene profiles. In wild type mice Alx3 is expressed in hypothalamic arcuate nucleus neurons, but not in major peripheral metabolic organs. Functional diffusion-weighted magnetic resonance imaging reveals selective hypothalamic responses to fasting in the arcuate nucleus of Alx3-deficient mice. Additionally, altered expression of proopiomelanocortin and melanocortin-3 receptor mRNA in the hypothalamus suggests impaired regulation of feeding behavior. This study highlights the crucial role for Alx3 in governing food intake, energy homeostasis, and metabolic nutrient partitioning, thereby influencing body mass composition.
Identifiants
pubmed: 39129011
doi: 10.1007/s00018-024-05384-z
pii: 10.1007/s00018-024-05384-z
doi:
Substances chimiques
Homeodomain Proteins
0
Transcription Factors
0
Pro-Opiomelanocortin
66796-54-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
343Informations de copyright
© 2024. The Author(s).
Références
Mirasierra M, Vallejo M (2006) The homeoprotein Alx3 expressed in pancreatic β-cells regulates insulin gene transcription by interacting with the basic helix-loop-helix protein E47. Mol Endocrinol 20:2876–2889. https://doi.org/10.1210/me.2005-0472
doi: 10.1210/me.2005-0472
pubmed: 16825292
Fernández-Pérez A, Vallejo M (2014) Pdx1 and USF transcription factors co-ordinately regulate Alx3 gene expression in pancreatic β-cells. Biochem J 463:287–296. https://doi.org/10.1042/BJ20140643
doi: 10.1042/BJ20140643
pubmed: 25040025
García-Sanz P, Mirasierra M, Vallejo M (2017) Embryonic defence mechanisms against glucose-dependent oxidative stress require enhanced expression of Alx3 to prevent malformations during diabetic pregnancy. Sci Rep 7:389. https://doi.org/10.1038/s41598-017-00334-1
doi: 10.1038/s41598-017-00334-1
pubmed: 28341857
pmcid: 5428206
Mirasierra M, Vallejo M (2016) Glucose-dependent downregulation of glucagon gene expression mediated by selective interactions between ALX3 and PAX6 in mouse alpha cells. Diabetologia 59:766–775. https://doi.org/10.1007/s00125-015-3849-4
doi: 10.1007/s00125-015-3849-4
pubmed: 26739814
Mirasierra M, Fernández-Pérez A, Díaz-Prieto N, Vallejo M (2011) Alx3-deficient mice exhibit decreased insulin in beta cells, altered glucose homeostasis and increased apoptosis in pancreatic islets. Diabetologia 54:403–414. https://doi.org/10.1007/s00125-010-1975-6
doi: 10.1007/s00125-010-1975-6
pubmed: 21104068
Beverdam A, Brouwer A, Reijnen M, Korving J, Meijlink F (2001) Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. Development 128:3975–3986. https://doi.org/10.1242/dev.128.20.3975
doi: 10.1242/dev.128.20.3975
pubmed: 11641221
Lakhwani S, Garcia-Sanz P, Vallejo M (2010) Alx3-deficient mice exhibit folic acid-resistant craniofacial midline and neural tube closure defects. Dev Biol 344:869–880. https://doi.org/10.1016/j.ydbio.2010.06.002
doi: 10.1016/j.ydbio.2010.06.002
pubmed: 20534379
Mallarino R, Henegar C, Mirasierra M et al (2016) Developmental mechanisms of stripe patterns in rodents. Nature 359:518–523. https://doi.org/10.1038/nature20109
doi: 10.1038/nature20109
Twigg SRF, Versnel SL, Nurnberg G et al (2009) Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by recessive mutations in the ALX3 homeobox gene. Am J Hum Genet 84:1–8. https://doi.org/10.1016/j.ajhg.2009.04.009
doi: 10.1016/j.ajhg.2009.04.009
García MC, Wernstedt I, Berndtsson A et al (2006) Mature-onset obesity in interleukin-1 receptor I knockout mice. Diabetes 55:1205–1213. https://doi.org/10.2337/db05-1304
doi: 10.2337/db05-1304
pubmed: 16644674
Tang H, Vasselli JR, Wu EX, Boozer C, Gallagher D (2002) High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats. Am J Physiol Regul Integr Comp Physiol 282:R890–R899. https://doi.org/10.1152/ajpregu.0527.2001
doi: 10.1152/ajpregu.0527.2001
pubmed: 11832412
Solís O, García-Montes JR, García-Sanz P et al (2017) Human COMT over-expression confers a heightened susceptibility to dyskinesia in mice. Neurobiol Dis 102:133–139. https://doi.org/10.1016/j.nbd.2017.03.006
doi: 10.1016/j.nbd.2017.03.006
pubmed: 28315782
pmcid: 5481205
Del Río-Martín A, Pérez-Taboada I, Fernandez-Pérez A, Moratalla R, De la Villa P, Vallejo M (2019) Hypomorphic expression of Pitx3 disrupts circadian clocks and prevents metabolic entrainment of Energy Expenditure. Cell Rep 29:3678–3692. https://doi.org/10.1016/j.celrep.2019.11.027
doi: 10.1016/j.celrep.2019.11.027
pubmed: 31825844
Perez LJ, Rios L, Trivedi P et al (2017) Validation of optimal reference genes for quantitative real time PCR in muscle and adipose tissue for obesity and diabetes research. Sci Rep 7:3612. https://doi.org/10.1038/s41598-017-03730-9
doi: 10.1038/s41598-017-03730-9
pubmed: 28620170
pmcid: 5472619
Livak K, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2
doi: 10.1006/meth.2001.1262
pubmed: 11846609
Cowley MA, Smart JL, Rubinstein M et al (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480–484. https://doi.org/10.1038/35078085
doi: 10.1038/35078085
pubmed: 11373681
Estañ MC, Fernández-Núñez E, Zaki MS et al (2019) Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy. Nat Commun 10:797. https://doi.org/10.1038/s41467-019-08548-9
doi: 10.1038/s41467-019-08548-9
pubmed: 30770808
pmcid: 6377633
Benoit B, Meugnier E, Castelli M et al (2017) Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Nat Med 23:990–996. https://doi.org/10.1038/nm.4363
doi: 10.1038/nm.4363
pubmed: 28650457
Molinero A, Fernandez-Pérez A, Mogas A et al (2017) Role of muscle IL-6 in gender-specific metabolism in mice. PLoS ONE 12:e0173675. https://doi.org/10.1371/journal.pone.0173675
doi: 10.1371/journal.pone.0173675
pubmed: 28319140
pmcid: 5358764
García-Sanz P, Fernández-Pérez A, Vallejo M (2013) Differential configurations involving binding of USF transcription factors and Twist1 regulate Alx3 promoter activity in mesenchymal and pancreatic cells. Biochem J 450:199–208. https://doi.org/10.1042/BJ20120962
doi: 10.1042/BJ20120962
pubmed: 23181698
Cantó C, Suárez E, Lizcano JM et al (2004) Neuregulin signaling on glucose transport in muscle cells. J Biol Chem 279:12260–12268. https://doi.org/10.1074/jbc.M308554200
doi: 10.1074/jbc.M308554200
pubmed: 14711829
Steculorum SM, Paeger L, Bremser S et al (2015) Hypothalamic UDP increases in obesity and promotes feeding via P2Y6-Dependent activation of AgRP neurons. Cell 162:1404–1417. https://doi.org/10.1016/j.cell.2015.08.032
doi: 10.1016/j.cell.2015.08.032
pubmed: 26359991
Ma Y, Smith D, Hof PR et al (2008) In vivo 3D digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Front Neuroanat 2:1. https://doi.org/10.3389/neuro.05.001.2008
doi: 10.3389/neuro.05.001.2008
pubmed: 18958199
pmcid: 2525925
Lizarbe B, Benítez A, Sánchez-Montañés M et al (2013) Imaging hypothalamic activity using diffusion weighted magnetic resonance imaging in the mouse and human brain. NeuroImage 64:448–457. https://doi.org/10.1016/j.neuroimage.2012.09.033
doi: 10.1016/j.neuroimage.2012.09.033
pubmed: 23000787
Franklin KBJ, Paxinos G (2008) The mouse brain in stereotaxic coordinates. Elsevier, Amsterdam
Lizarbe B, Fernández-Pérez A, Caz V et al (2019) Systemic Glucose Administration Alters Water Diffusion and Microvascular Blood Flow in mouse hypothalamic nuclei - an fMRI study. Front Neurosci 13:921. https://doi.org/10.3389/fnins.2019.00921
doi: 10.3389/fnins.2019.00921
pubmed: 31551685
pmcid: 6733885
Rubio WB, Cortopassi MD, Banks AS (2023) Indirect calorimetry to assess Energy Balance in mice: Measurement and Data Analysis. Methods Mol Biol 2662:103–115. https://doi.org/10.1007/978-1-0716-3167-6_9
doi: 10.1007/978-1-0716-3167-6_9
pubmed: 37076674
Campillo BW, Galguera D, Cerdán S, López-Larrubia P, Lizarbe B (2022) Short-term high-fat diet alters the mouse brain magnetic resonance imaging parameters consistently with neuroinflammation on males and metabolic rearrangements on females. A pre-clinical study with an optimized selection of linear mixed-effects models. Front NeuroSci 16:1025108. https://doi.org/10.3389/fnins.2022.1025108
doi: 10.3389/fnins.2022.1025108
pubmed: 36507349
pmcid: 9729798
Yu S, Meng S, Xiang M, Ma H (2021) Phosphoenolpyruvate carboxykinase in cell metabolism: roles and mechanisms beyond gluconeogenesis. Mol Metabolism 53:101257. https://doi.org/10.1016/j.molmet.2021.101257
doi: 10.1016/j.molmet.2021.101257
Zeng W, Pirzgalska RM, Pereira MM et al (2015) Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell 163:84–94. https://doi.org/10.1016/j.cell.2015.08.055
doi: 10.1016/j.cell.2015.08.055
pubmed: 26406372
Hatori M, Vollmers C, Zarrinpar A et al (2012) Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15:848–860. https://doi.org/10.1016/j.cmet.2012.04.019
doi: 10.1016/j.cmet.2012.04.019
pubmed: 22608008
pmcid: 3491655
Vaughan SK, Sutherland NM, Valdez G (2019) Attenuating Cholinergic Transmission increases the number of Satellite cells and preserves muscle Mass in Old Age. Front Aging Neurosci 11:262. https://doi.org/10.3389/fnagi.2019.00262
doi: 10.3389/fnagi.2019.00262
pubmed: 31616286
pmcid: 6768977
Moresi V, Williams AH, Meadows E et al (2010) Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell 143:35–45. https://doi.org/10.1016/j.cell.2010.09.004
doi: 10.1016/j.cell.2010.09.004
pubmed: 20887891
pmcid: 2982779
Méjat A, Ramond F, Bassel-Duby R, Khochbin S, Olson EN, Schaeffer L (2005) Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nat Neurosci 8:313–321. https://doi.org/10.1038/nn1408
doi: 10.1038/nn1408
pubmed: 15711539
Henderson CE, Phillips HS, Pollock RA et al (1994) GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. Science 266:1062–1064. https://doi.org/10.1126/science.7973664
doi: 10.1126/science.7973664
pubmed: 7973664
Stanga S, Brambilla L, Tasiaux B et al (2018) A role for GDNF and Soluble APP as biomarkers of amyotrophic lateral sclerosis pathophysiology. Front Neurol 9:384. https://doi.org/10.3389/fneur.2018.00384
doi: 10.3389/fneur.2018.00384
pubmed: 29899726
pmcid: 5988896
Baczek J, Silkiewicz M, Wojszel ZB (2020) Myostatin as a biomarker of muscle wasting and other pathologies-State of the art and knowledge gaps. Nutrients 12:E2401. https://doi.org/10.3390/nu12082401
doi: 10.3390/nu12082401
Kim JK, Jha NN, Feng Z et al (2020) Muscle-specific SMN reduction reveals motor neuron-independent disease in spinal muscular atrophy models. J Clin Invest 130:1271–1287. https://doi.org/10.1172/JCI131989
doi: 10.1172/JCI131989
pubmed: 32039917
pmcid: 7269591
Alkaslasi MR, Piccus ZE, Hareendran S et al (2021) Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord. Nat Commun 12:2471. https://doi.org/10.1038/s41467-021-22691-2
doi: 10.1038/s41467-021-22691-2
pubmed: 33931636
pmcid: 8087807
Khan MM, Lustrino D, Silveira WA et al (2016) Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease. Proc Natl Acad Sci U S A 113:746–750. https://doi.org/10.1073/pnas.1524272113
doi: 10.1073/pnas.1524272113
pubmed: 26733679
pmcid: 4725522
Rodrigues ACZ, Messi ML, Wang ZM et al (2019) The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability. Acta Physiol 225:e13195. https://doi.org/10.1111/apha.13195
doi: 10.1111/apha.13195
Lorenzo-Martín LF, Menacho-Márquez M, Fabbiano S et al (2019) Vagal afferents contribute to sympathoexcitation-driven metabolic dysfunctions. J Endocrinol 240:483–496. https://doi.org/10.1530/JOE-18-0623
doi: 10.1530/JOE-18-0623
pubmed: 30703063
pmcid: 6368248
Krashes MJ, Shah BP, Madara JC et al (2014) An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature 507:238–242. https://doi.org/10.1038/nature12956
doi: 10.1038/nature12956
pubmed: 24487620
pmcid: 3955843
Orozco-Solís R, Aguilar-Arnal L, Murakami M et al (2016) The circadian clock in the ventromedial hypothalamus controls cyclic energy expenditure. Cell Metab 23:467–478. https://doi.org/10.1016/j.cmet.2016.02.003
doi: 10.1016/j.cmet.2016.02.003
pubmed: 26959185
pmcid: 5373494
Schneeberger M, Gomis R, Claret M (2014) Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J Endocrinol 220:T25–T46. https://doi.org/10.1530/JOE-13-0398
doi: 10.1530/JOE-13-0398
pubmed: 24222039
Bischof JM, Stewart CL, Wevrick R (2007) Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome. Hum Mol Genet 16:2713–2719. https://doi.org/10.1093/hmg/ddm225
doi: 10.1093/hmg/ddm225
pubmed: 17728320
Oncul M, Dilsiz P, Oz EA et al (2018) Impaired melanocortin pathway function in Prader-Willi syndrome gene-Magel2 deficient mice. Hum Mol Genet 27:3129–3136. https://doi.org/10.1093/hmg/ddy216
doi: 10.1093/hmg/ddy216
pubmed: 29878108
Orquera DP, Tavella MB, de Souza FSJ, Nasif S, Low MJ, Rubinstein M (2019) The Homeodomain transcription factor NKX2.1 is essential for the early specification of Melanocortin Neuron Identity and activates Pomc expression in the developing hypothalamus. J Neurosci 39:4023–4035. https://doi.org/10.1523/jneurosci.2924-18.2019
doi: 10.1523/jneurosci.2924-18.2019
pubmed: 30886014
pmcid: 6529873
Jin T, Kim SG (2008) Functional changes of apparent diffusion coefficient during visual stimulation investigated by diffusion-weighted gradient-echo fMRI. NeuroImage 41:801–812. https://doi.org/10.1016/j.neuroimage.2008.03.014
doi: 10.1016/j.neuroimage.2008.03.014
pubmed: 18450483
Abe Y, Tsurugizawa T, Le Bihan D (2017) Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia. PLoS Biol 15:e2001494. https://doi.org/10.1371/journal.pbio.2001494
doi: 10.1371/journal.pbio.2001494
pubmed: 28406906
pmcid: 5390968
Williams KW, Elmquist JK (2012) From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci 15:1350–1355. https://doi.org/10.1038/nn.3217
doi: 10.1038/nn.3217
pubmed: 23007190
pmcid: 3763714
Lau J, Herzog H (2014) CART in the regulation of appetite and energy homeostasis. Front Neurosci 8:313. https://doi.org/10.3389/fnins.2014.00313
doi: 10.3389/fnins.2014.00313
pubmed: 25352770
pmcid: 4195273
Yang L, Qi Y, Yang Y (2015) Astrocytes control food intake by inhibiting AGRP neuron activity via adenosine A1 receptors. Cell Rep 11:798–807. https://doi.org/10.1016/j.celrep.2015.04.002
doi: 10.1016/j.celrep.2015.04.002
pubmed: 25921535
Secher A, Jelsing J, Baquero AF et al (2014) The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest 124:4473–4488. https://doi.org/10.1172/JCI75276
doi: 10.1172/JCI75276
pubmed: 25202980
pmcid: 4215190
Teng R, Gavrilova O, Suzuki N et al (2011) Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production. Nat Commun 2:250. https://doi.org/10.1038/ncomms1526
doi: 10.1038/ncomms1526
Butler AA, Kesterson RA, Khong K et al (2000) A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141:3518–3521. https://doi.org/10.1210/endo.141.9.7791
doi: 10.1210/endo.141.9.7791
pubmed: 10965927
Chen AS, Marsh DJ, Trumbauer ME et al (2000) Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 26:97–102. https://doi.org/10.1038/79254
doi: 10.1038/79254
pubmed: 10973258
Marks DL, Hruby V, Brookhart G, Cone RD (2006) The regulation of food intake by selective stimulation of the type 3 melanocortin receptor (MC3R). Peptides 27:259–264. https://doi.org/10.1016/j.peptides.2005.01.025
doi: 10.1016/j.peptides.2005.01.025
pubmed: 16274853
Lee M, Kim A, Conwell IM et al (2008) Effects of selective modulation of the central melanocortin-3-receptor on food intake and hypothalamic POMC expression. Peptides 29:440–447. https://doi.org/10.1016/j.peptides.2007.11.005
doi: 10.1016/j.peptides.2007.11.005
pubmed: 18155809
Montgomery MK, Hallahan NL, Brown SH et al (2013) Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding. Diabetologia 56:1129–1139. https://doi.org/10.1007/s00125-013-2846-8
doi: 10.1007/s00125-013-2846-8
pubmed: 23423668
Chua S, Li Y, Liu SM et al (2010) A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8. Kidney Int 78:453–462. https://doi.org/10.1038/ki.2010.160
doi: 10.1038/ki.2010.160
pubmed: 20520596
pmcid: 3998677
Krashes MJ, Lowell BB, Garfield AS (2016) Melanocortin-4 receptor-regulated energy homeostasis. Nat Neurosci 19:206–219. https://doi.org/10.1038/nn.4202
doi: 10.1038/nn.4202
pubmed: 26814590
pmcid: 5244821
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155–157. https://doi.org/10.1038/509
doi: 10.1038/509
pubmed: 9620771
Lee M, Poh LK, Kek BL, Loke KY (2008) Novel melanocortin 4 receptor mutations in severely obese children. Clin Endocrinol 68:529–535. https://doi.org/10.1111/j.1365-2265.2007.03071.x
doi: 10.1111/j.1365-2265.2007.03071.x
Yu H, Chhabra KH, Thompson Z et al (2020) Hypothalamic POMC deficiency increases circulating adiponectin despite obesity. Mol Metab 35:100957. https://doi.org/10.1016/j.molmet.2020.01.021
doi: 10.1016/j.molmet.2020.01.021
pubmed: 32244188
pmcid: 7082555
Timper K, Brüning JC (2017) Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis Model Mech 10:679–689. https://doi.org/10.1242/dmm.026609
doi: 10.1242/dmm.026609
pubmed: 28592656
pmcid: 5483000
Ghamari-Langroudi M, Cakir I, Lippert RN et al (2018) Regulation of energy rheostasis by the melanocortin-3 receptor. Sci Adv 4:eaat0866. https://doi.org/10.1126/sciadv.aat0866
doi: 10.1126/sciadv.aat0866
pubmed: 30140740
pmcid: 6105298
Di Micioni E, Botticelli L, Tomassoni D, Tayebati SK, Di Micioni MV, Cifani C (2020) The Melanocortin System behind the dysfunctional eating behaviors. Nutrients 12:3502. https://doi.org/10.3390/nu12113502
doi: 10.3390/nu12113502
Nogueiras R, Wiedmer P, Perez-Tilve D et al (2007) The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest 117:3475–3488. https://doi.org/10.1172/JCI31743
doi: 10.1172/JCI31743
pubmed: 17885689
pmcid: 1978426
Morgan DA, McDaniel LN, Yin T et al (2015) Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus. Diabetes 64:1976–1987. https://doi.org/10.2337/db14-1257
doi: 10.2337/db14-1257
pubmed: 25605803
pmcid: 4439564
Braun TP, Marks DL (2011) Hypothalamic regulation of muscle metabolism. Curr Opin Clin Nutr Metab Care 14:237–242. https://doi.org/10.1097/MCO.0b013e328345bbcd
doi: 10.1097/MCO.0b013e328345bbcd
pubmed: 21502918
Lin EE, Scott-Solomon E, Kuruvilla R (2021) Peripheral innervation in the regulation of glucose homeostasis. Trends Neurosci 44:189–202. https://doi.org/10.1016/j.tins.2020.10.015
doi: 10.1016/j.tins.2020.10.015
pubmed: 33229051
Franckhauser S, Munoz S, Elias I, Ferre T, Bosch F (2006) Adipose overexpression of phosphoenolpyruvate carboxykinase leads to high susceptibility to diet-induced insulin resistance and obesity. Diabetes 55:273–280. https://doi.org/10.2337/diabetes.55.02.06.db05-0482
doi: 10.2337/diabetes.55.02.06.db05-0482
pubmed: 16443757
Frasson D, Boschini RP, Chaves VE et al (2012) The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats. Metabolism 61:1473–1485. https://doi.org/10.1016/j.metabol.2012.03.014
doi: 10.1016/j.metabol.2012.03.014
pubmed: 22592131
Klein S, Gastaldelli A, Yki-Järvinen H, Scherer PE (2022) Why does obesity cause diabetes? Cell Metabol 34:11–20. https://doi.org/10.1016/j.cmet.2021.12.012
doi: 10.1016/j.cmet.2021.12.012
Stern JH, Rutkowski JM, Scherer PE (2016) Adiponectin, Leptin, and fatty acids in the Maintenance of Metabolic Homeostasis through adipose tissue crosstalk. Cell Metab 23:770–784. https://doi.org/10.1016/j.cmet.2016.04.011
doi: 10.1016/j.cmet.2016.04.011
pubmed: 27166942
pmcid: 4864949
Zurlo F, Larson K, Bogardus C, Ravussin E (1990) Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 85:1423–1427. https://doi.org/10.1172/JCI114857
doi: 10.1172/JCI114857
Mengeste AM, Rustan AC, Lund J (2021) Skeletal muscle energy metabolism in obesity. Obesity 29:1582–1595. https://doi.org/10.1002/oby.23227
doi: 10.1002/oby.23227
pubmed: 34464025
Yagi S, Kadota M, Aihara KI et al (2014) Association of lower limb muscle mass and energy expenditure with visceral fat mass in healthy men. Diabetol Metab Syndr 26:27. https://doi.org/10.1186/1758-5996-6-27
doi: 10.1186/1758-5996-6-27
Benarroch E (2024) What is the role of the sympathetic system in skeletal muscle? Neurology 102:e209488. https://doi.org/10.1212/wnl.0000000000209488
doi: 10.1212/wnl.0000000000209488
pubmed: 38710007
Delbono O, Rodrigues ACZ, Bonilla HJ, Messi ML (2021) The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia. Ageing Res Rev 67:101305. https://doi.org/10.1016/j.arr.2021.101305
doi: 10.1016/j.arr.2021.101305
pubmed: 33610815
pmcid: 8049122
Straka T, Vita V, Prokshi K et al (2018) Postnatal Development and Distribution of Sympathetic Innervation in mouse skeletal muscle. Int J Mol Sci 1935. https://doi.org/10.3390/ijms19071935
Wang ZM, Messi ML, Rodrigues ACZ, Delbono O (2022) Skeletal muscle sympathetic denervation disrupts the neuromuscular junction postterminal organization: a single-cell quantitative approach. Mol Cell Neurosci 120:103730. https://doi.org/10.1016/j.mcn.2022.103730
doi: 10.1016/j.mcn.2022.103730
pubmed: 35489637
pmcid: 9793435
Vanhaesebrouck AE, Beeson D (2019) The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies. Curr Opin Neurol 32:696–703. https://doi.org/10.1097/WCO.0000000000000736
doi: 10.1097/WCO.0000000000000736
pubmed: 31361628
pmcid: 6735524
McMacken GM, Spendiff S, Whittaker RG et al (2019) Salbutamol modifies the neuromuscular junction in a mouse model of ColQ myasthenic syndrome. Hum Mol Genet 28:2339–2351. https://doi.org/10.1093/hmg/ddz059
doi: 10.1093/hmg/ddz059
pubmed: 31220253
pmcid: 6606850
Wang ZM, Messi ML, Grinevich V, Budygin E, Delbono O (2020) Postganglionic sympathetic neurons, but not locus coeruleus optostimulation, activates neuromuscular transmission in the adult mouse in vivo. Mol Cell Neurosci 109:103563. https://doi.org/10.1016/j.mcn.2020.103563
doi: 10.1016/j.mcn.2020.103563
pubmed: 33039519
pmcid: 8049128
Joassard OR, Bélanger G, Karmouch J et al (2015) HuR mediates changes in the Stability of AChR β-Subunit mRNAs after skeletal muscle denervation. J Neurosci 35:10949–10962. https://doi.org/10.1523/JNEUROSCI.1043-15.2015
doi: 10.1523/JNEUROSCI.1043-15.2015
pubmed: 26245959
pmcid: 6605275
Nishino T, Ranade SS, Pelonero A et al (2023) Single-cell multimodal analyses reveal epigenomic and transcriptomic basis for birth defects in maternal diabetes. Nat Cardiovasc Res 2:1190–1203. https://doi.org/10.1038/s44161-023-00367-y
doi: 10.1038/s44161-023-00367-y