Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance.

Adipose Tissue, White / metabolism Animals Diet, High-Fat / adverse effects Energy Metabolism / physiology Insulin Resistance / physiology Male Mast Cells / metabolism Mice, Inbred C57BL Mice, Knockout Obesity / etiology Serotonin / biosynthesis Thermogenesis Triglycerides / metabolism Tryptophan Hydroxylase / genetics Uncoupling Protein 1 / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
23 01 2020
Historique:
received: 23 07 2019
accepted: 16 12 2019
entrez: 25 1 2020
pubmed: 25 1 2020
medline: 25 4 2020
Statut: epublish

Résumé

Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1

Identifiants

DOI: 10.1038/s41467-019-14080-7 PMID: 31974364 PMC: PMC6978527
pubmed: 31974364
doi: 10.1038/s41467-019-14080-7
pii: 10.1038/s41467-019-14080-7
pmc: PMC6978527
doi:

Substances chimiques

Triglycerides 0
Ucp1 protein, mouse 0
Uncoupling Protein 1 0
Serotonin 333DO1RDJY
Tph1 protein, mouse EC 1.14.16.4
Tryptophan Hydroxylase EC 1.14.16.4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

463

Subventions

Organisme : CIHR
Pays : Canada

Références

Reilly, S. M. & Saltiel, A. R. Adapting to obesity with adipose tissue inflammation. Nat. Rev. Endocrinol. 13, 633–643 (2017).
pubmed: 28799554 doi: 10.1038/nrendo.2017.90
The GBD 2015 Obesity Collaborators, A. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 311, 13–27 (2017).
doi: 10.1056/NEJMoa1614362
Chouchani, E. T., Kazak, L. & Spiegelman, B. M. New advances in adaptive thermogenesis: ucp1 and beyond. Cell Metab. 29, 27–37 (2018).
Kajimura, S., Spiegelman, B. M. & Seale, P. Review brown and beige fat: physiological roles beyond heat generation. Cell Metab. 22, 546–559 (2015).
pubmed: 26445512 pmcid: 4613812 doi: 10.1016/j.cmet.2015.09.007
Kajimura, S. & Saito, M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu. Rev. Physiol. 76, 225–249 (2014).
pubmed: 24188710 doi: 10.1146/annurev-physiol-021113-170252 pmcid: 24188710
Shabalina, I. G. et al. UCP1 in Brite/Beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 5, 1196–1203 (2013).
pubmed: 24290753 doi: 10.1016/j.celrep.2013.10.044
Sharp, L. Z. et al. Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS ONE 7, e49452 (2012).
pubmed: 23166672 pmcid: 3500293 doi: 10.1371/journal.pone.0049452
Wu, J. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376 (2012).
pubmed: 22796012 pmcid: 3402601 doi: 10.1016/j.cell.2012.05.016
Jespersen, N. Z. et al. A classical brown adipose tissue mrna signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab. 17, 798–805 (2013).
pubmed: 23663743 doi: 10.1016/j.cmet.2013.04.011 pmcid: 23663743
Cypess, A. M. et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509–1517 (2009).
pubmed: 19357406 pmcid: 2859951 doi: 10.1056/NEJMoa0810780
van Marken Lichtenbelt, W. D. et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500–1508 (2009).
pubmed: 19357405 doi: 10.1056/NEJMoa0808718 pmcid: 19357405
Leitner, B. P. et al. Mapping of human brown adipose tissue in lean and obese young men. Proc. Natl Acad. Sci. USA 114, 8649–8654 (2017).
doi: 10.1073/pnas.1705287114
Crane, J. D. et al. Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat. Med. 21, 166–172 (2015).
doi: 10.1038/nm.3766
Oh, C.-M. et al. Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nat. Commun. 6, 6794 (2015).
pmcid: 4403443 doi: 10.1038/ncomms7794
Mawe, G. M. & Hoffman, J. M. Serotonin signalling in the gut-functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 10, 473–486 (2013).
pubmed: 23797870 pmcid: 4048923 doi: 10.1038/nrgastro.2013.105
Yabut, J. M. et al. Emerging roles for serotonin in regulating metabolism: new implications for an ancient molecule. Endocr. Rev. 40, 1092–1107 (2019).
pubmed: 30901029 doi: 10.1210/er.2018-00283 pmcid: 30901029
Sumara, G., Sumara, O., Kim, J. K. & Karsenty, G. Gut-derived serotonin is a multifunctional determinant to fasting adaptation. Cell Metab. 16, 588–600 (2012).
pubmed: 23085101 pmcid: 3696514 doi: 10.1016/j.cmet.2012.09.014
Jeffery, E. et al. Characterization of Cre recombinase models for the study of adipose tissue. Adipocyte 3, 206–211 (2014).
pubmed: 25068087 pmcid: 4110097 doi: 10.4161/adip.29674
Feldmann, H. M., Golozoubova, V., Cannon, B. & Nedergaard, J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 9, 203–209 (2009).
pubmed: 19187776 doi: 10.1016/j.cmet.2008.12.014 pmcid: 19187776
Roh, H. C. et al. Warming induces significant reprogramming of beige, but not brown, adipocyte cellular identity. Cell Metab. 27, 1121–1137.e5 (2018).
pubmed: 29657031 pmcid: 5932137 doi: 10.1016/j.cmet.2018.03.005
Wu, C. et al. BioGPS: An extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol. 10, (2009).
pmcid: 3091323 doi: 10.1186/gb-2009-10-11-r130
Kalesnikoff, J. & Galli, S. J. New developments in mast cell biology. Nat. Immunol. 9, 1215–1223 (2008).
pmcid: 2856637 doi: 10.1038/ni.f.216
Liu, Q. et al. Discovery and characterization of novel tryptophan hydroxylase inhibitors that selectively inhibit serotonin synthesis in the gastrointestinal tract. J. Pharmacol. Exp. Ther. 325, 47–55 (2008).
doi: 10.1124/jpet.107.132670
Hellman, B., Larsson, S. & Westman, S. Mast cell content and fatty acid metabolism in the epididymal fat pad of obese mice. Acta Physiol. Scand. 58, 255–262 (1963).
pubmed: 13953609 doi: 10.1111/j.1748-1716.1963.tb02647.x pmcid: 13953609
Divoux, A. et al. Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes. J. Clin. Endocrinol. Metab. 97, E1677–E1685 (2012).
pubmed: 22745246 doi: 10.1210/jc.2012-1532 pmcid: 22745246
Zhou, Y. et al. Leptin deficiency shifts mast cells toward anti-inflammatory actions and protects mice from obesity and diabetes by polarizing M2 macrophages. Cell Metab. 22, 1–14 (2015).
doi: 10.1016/j.cmet.2015.09.013
Liu, J. et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15, 940–945 (2009).
pubmed: 19633655 pmcid: 2736875 doi: 10.1038/nm.1994
Gutierrez, D. A., Muralidhar, S., Feyerabend, T. B., Herzig, S. & Rodewald, H.-R. Hematopoietic kit deficiency, rather than lack of mast cells, protects mice from obesity and insulin resistance. Cell Metab. 21, 678–691 (2015).
pubmed: 25955205 doi: 10.1016/j.cmet.2015.04.013 pmcid: 25955205
Crane, J. D., Mottillo, E. P., Farncombe, T. H., Morrison, K. M. & Steinberg, G. R. A standardized infrared imaging technique that specifically detects UCP1-mediated thermogenesis invivo. Mol. Metab. 3, 490–494 (2014).
pmcid: 4060225 doi: 10.1016/j.molmet.2014.04.007
Zhang, X. et al. Functional inactivation of mast cells enhances subcutaneous adipose tissue browning in mice. Cell Rep. 28, 792–803.e4 (2019).
pmcid: 6662660 doi: 10.1016/j.celrep.2019.06.044
Cano, G. et al. Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure. J. Comp. Neurol. 460, 303–326 (2003).
doi: 10.1002/cne.10643
Madden, C. J. & Morrison, S. F. Serotonin potentiates sympathetic responses evoked by spinal NMDA. J. Physiol. 577, 525–537 (2006).
pmcid: 1890434 doi: 10.1113/jphysiol.2006.116574 pubmed: 1890434
Madden, C. J. & Morrison, S. F. Endogenous activation of spinal 5-hydroxytryptamine (5-HT) receptors contributes to the thermoregulatory activation of brown adipose tissue. AJP Regul. Integr. Comp. Physiol. 298, R776–R783 (2010).
doi: 10.1152/ajpregu.00614.2009
McGlashon, J. M. et al. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis. Cell Metab. 21, 692–705 (2015).
pmcid: 4565052 doi: 10.1016/j.cmet.2015.04.008 pubmed: 4565052
López, M. Hypothalamic AMPK and energy balance. Eur. J. Clin. Invest. 48, 1–10 (2018).
doi: 10.1111/eci.12996
Mottillo, E. P. et al. Lack of adipocyte AMPK exacerbates insulin resistance and hepatic steatosis through brown and beige adipose tissue function. Cell Metab. 24, 118–129 (2016).
pubmed: 27411013 pmcid: 5239668 doi: 10.1016/j.cmet.2016.06.006
Hu, F., Xu, Y. & Liu, F. Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis. Am. J. Physiol. - Endocrinol. Metab. 310, E994–E1002 (2016).
pubmed: 27166282 pmcid: 4935144 doi: 10.1152/ajpendo.00121.2016
Polak, P. et al. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 8, 399–410 (2008).
pubmed: 19046571 doi: 10.1016/j.cmet.2008.09.003 pmcid: 19046571
Jung, S. M. et al. Non-canonical mTORC2 signaling regulates brown adipocyte lipid catabolism through SIRT6-FoxO1. Mol. Cell 75, 807–822.e8 (2019).
pubmed: 31442424 doi: 10.1016/j.molcel.2019.07.023
Li, Y., Calvo, S. E., Gutman, R., Liu, J. S. & Mootha, V. K. Expansion of biological pathways based on evolutionary inference. Cell 158, 213–225 (2014).
pubmed: 24995987 pmcid: 4171950 doi: 10.1016/j.cell.2014.05.034
Ikeda, K. et al. UCP1-independent signaling involving SERCA2bmediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat. Med. 23, 1454–1465 (2017).
pubmed: 29131158 pmcid: 5727902 doi: 10.1038/nm.4429
Chen, Y. et al. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature 565, 180–185 (2019).
pubmed: 30568302 doi: 10.1038/s41586-018-0801-z pmcid: 30568302
Lilla, J. N. et al. Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1 fl/fl mice. Blood 118, 6930–6938 (2011).
pubmed: 22001390 pmcid: 3245213 doi: 10.1182/blood-2011-03-343962
Nowak, E. C. et al. Tryptophan hydroxylase-1 regulates immune tolerance and inflammation. J. Exp. Med. 209, 2127–2135 (2012).
pmcid: 3478935 doi: 10.1084/jem.20120408
Reber, L. L., Marichal, T. & Galli, S. J. New models for analyzing mast cell functions in vivo. Trends Immunol. 33, 613–625 (2012).
pubmed: 23127755 pmcid: 3572764 doi: 10.1016/j.it.2012.09.008
Pettersson, U. S., Waldén, T. B., Carlsson, P. O., Jansson, L. & Phillipson, M. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS ONE 7, e46057 (2012).
Gaudenzio, N. et al. Analyzing the functions of mast cells in vivo using mast cell knock-in mice. J. Vis. Exp. 99, 1–11 (2015).
Watts, S. W., Morrison, S. F., Davis, R. P. & Barman, S. M. Serotonin and blood pressure regulation. Pharmacol. Rev. 64, 359–388 (2012).
pubmed: 22407614 pmcid: 3310484 doi: 10.1124/pr.111.004697
Morecroft, I. et al. Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension. Hypertension 49, 232–236 (2007).
pubmed: 17130306 doi: 10.1161/01.HYP.0000252210.58849.78 pmcid: 17130306
Kay, J. M., Keane, P. M. & Suyama, K. L. Pulmonary hypertension induced in rats by monocrotaline and chronic hypoxia is reduced by p-chlorophenylalanine. Respiration 47, 48–56 (1985).
pubmed: 3156395 doi: 10.1159/000194748 pmcid: 3156395
Kushnir-Sukhov, N. M., Brown, J. M., Wu, Y., Kirshenbaum, A. & Metcalfe, D. D. Human mast cells are capable of serotonin synthesis and release. J. Allergy Clin. Immunol. 119, 498–499 (2007).
doi: 10.1016/j.jaci.2006.09.003
Côté, F. et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc. Natl Acad. Sci. USA 100, 13525–13530 (2003).
pubmed: 14597720 doi: 10.1073/pnas.2233056100 pmcid: 14597720
Yadav, V. K. et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135, 825–837 (2008).
pubmed: 19041748 pmcid: 2614332 doi: 10.1016/j.cell.2008.09.059
Grimbaldeston, M. A. et al. Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am. J. Pathol. 167, 835–848 (2005).
pubmed: 16127161 pmcid: 1698741 doi: 10.1016/S0002-9440(10)62055-X
Kimura, I., Moritani, Y. & Tanizaki, Y. Basophils in bronchial asthma with reference to reagin‐type allergy. Clin. Exp. Allergy 3, 195–202 (1973).
doi: 10.1111/j.1365-2222.1973.tb01321.x
Wang, B. et al. Maternal retinoids increase PDGFRα+ progenitor population and beige adipogenesis in progeny by stimulating vascular development. EBioMedicine 18, 288–299 (2017).
pubmed: 28408241 pmcid: 5405191 doi: 10.1016/j.ebiom.2017.03.041
Folch, J., Lees, M. & Stanley, G. H. S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).

Auteurs

Julian M Yabut (JM)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.

Eric M Desjardins (EM)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.

Eric J Chan (EJ)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.

Emily A Day (EA)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.

Julie M Leroux (JM)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.

Bo Wang (B)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
ORCID: 0000-0003-0604-1607

Elizabeth D Crane (ED)

Department of Biology, Northeastern University, Boston, MA, 02115, USA.

Wesley Wong (W)

Department of Biology, Northeastern University, Boston, MA, 02115, USA.
ORCID: 0000-0003-3333-6689

Katherine M Morrison (KM)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Department of Pediatrics, McMaster University, 1280 Main St. W, Hamilton, ON, Canada, L8N 3Z5.
ORCID: 0000-0002-1737-256X

Justin D Crane (JD)

Department of Biology, Northeastern University, Boston, MA, 02115, USA.
ORCID: 0000-0002-5380-5676

Waliul I Khan (WI)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Farncombe Family Digestive Health Research Institute, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5.

Gregory R Steinberg (GR)

Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5. gsteinberg@mcmaster.ca.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5. gsteinberg@mcmaster.ca.
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON, Canada, L8N 3Z5. gsteinberg@mcmaster.ca.
ORCID: 0000-0001-5425-8275

Articles similaires

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Meal Timing and Anthropometric and Metabolic Outcomes: A Systematic Review and Meta-Analysis.

Hiu Yee Liu, Ashley A Eso, Nathan Cook et al.
1.00
Humans Meals Time Factors Female Adult

Classifications MeSH

questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux blanc › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Eucaryotes › Animaux › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Métabolisme › Métabolisme énergétique › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Insulinorésistance › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Mastocytes › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Sérotonine › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Phénomènes biologiques › Adaptation biologique › Adaptation physiologique › Régulation de la température corporelle › Thermogenèse › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Lipides › Glycérides › Triglycéride › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxygénases › Mixed function oxygenases › Tryptophane 5-monooxygenase › Genetic deletion of mast cell serotonin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Protéines de transport de la membrane mitochondriale › Protéines de découplage mitochondrial › Protéine-1 de découplage › Genetic deletion of mast cell serotonin...