Sex difference in physical activity, energy expenditure and obesity driven by a subpopulation of hypothalamic POMC neurons

Molecular Metabolism

Volumn 5, Issue 3, 2016, Pages 245-252

  Burke, Luke K ^a,b   Doslikova, Barbora ^b   D'Agostino, Giuseppe ^a,b   Greenwald Yarnell, Megan ^c   Georgescu, Teodora ^a   Chianese, Raffaella ^a   Martinez de Morentin, Pablo B ^a   Ogunnowo Bada, Emmanuel ^b   Cansell, Celine ^a   Valencia Torres, Lourdes ^a,b   Garfield, Alastair S ^b   Apergis Schoute, John ^b   Lam, Daniel D ^c   Speakman, John R ^d,e   Rubinstein, Marcelo ^f   Low, Malcolm J ^c   Rochford, Justin J ^a   Myers, Martin G ^c   Evans, Mark L ^b   Heisler, Lora K ^a  

^a ROWETT RESEARCH INSTITUTE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF ABERDEEN   (United Kingdom)

^e INSTITUTE OF GENETICS AND DEVELOPMENTAL BIOLOGY   (China)

^f INSTITUTO DE INVESTIGACIONES EN INGENIERÍA GENÉTICA Y BIOLOGÍA MOLECULAR   (Argentina)

Author keywords

5 HT2c receptor; Brown adipose tissue; Energy expenditure; Hyperinsulinemia; Hypothalamus; Obesity; Pro opiomelanocortin (Pomc); Sexual dimorphism

Indexed keywords

INSULIN; PROOPIOMELANOCORTIN; SEROTONIN 2C AGONIST;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APPETITE; ARCUATE NUCLEUS; ARTICLE; BODY WEIGHT; BROWN ADIPOSE TISSUE; CALORIC INTAKE; CONTROLLED STUDY; ENERGY BALANCE; ENERGY EXPENDITURE; FEEDING BEHAVIOR; FEMALE; FOOD INTAKE; HOMEOSTASIS; HORMONE SYNTHESIS; HUMAN; INSULIN SENSITIVITY; INSULIN TOLERANCE TEST; MALE; MOUSE; NERVE CELL; NONHUMAN; OBESITY; PHYSICAL ACTIVITY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PRO OPIOMELANOCORTIN NEURON; SEX DIFFERENCE;

EID: 84959140900     PISSN: None     EISSN: 22128778     Source Type: Journal    
DOI: 10.1016/j.molmet.2016.01.005     Document Type: Article

References (33)

1. World Health Organisation Global Health Observatory (GHO) obesity situation and trends 2014.
2. Williams K.W., Elmquist J.K. From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nature Neuroscience 2012 Oct, 15(10):1350-1355.
3. Ellacott K.L., Cone R.D. The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse models. Philosophical Transactions of the Royal Society B: Biological Sciences 2006 Jul, 361(1471):1265-1274.
4. Yeo G.S., Heisler L.K. Unraveling the brain regulation of appetite: lessons from genetics. Nature Neuroscience 2012 Oct, 15(10):1343-1349.
5. Ramachandrappa S., Farooqi I.S. Genetic approaches to understanding human obesity. Journal of Clinical Investigation 2011 Jun, 121(6):2080-2086.
6. Mori H., Inoki K., Münzberg H., Opland D., Faouzi M., Villanueva E.C., et al. Critical role for hypothalamic mTOR activity in energy balance. Cell Metabolism 2009 Apr, 9(4):362-374.
7. Yang S.B., Tien A.C., Boddupalli G., Xu A.W., Jan Y.N., Jan L.Y. Rapamycin ameliorates age-dependent obesity associated with increased mTOR signaling in hypothalamic POMC neurons. Neuron 2012 Aug, 75(3):425-436.
8. Newton A.J., Hess S., Paeger L., Vogt M.C., Fleming Lascano J., Nillni E.A., et al. AgRP innervation onto POMC neurons increases with age and is accelerated with chronic high-fat feeding in male mice. Endocrinology 2013 Jan, 154(1):172-183.
9. Heisler L.K., Cowley M.A., Tecott L.H., Fan W., Low M.J., Smart J.L., et al. Activation of central melanocortin pathways by fenfluramine. Science 2002 Jul, 297(5581):609-611.
10. Lam D.D., Przydzial M.J., Ridley S.H., Yeo G.S., Rochford J.J., O'Rahilly S., et al. Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology 2008 Mar, 149(3):1323-1328.
11. Burke L.K., Doslikova B., D'Agostino G., Garfield A.S., Farooq G., Burdakov D., et al. 5-HT obesity medication efficacy via POMC activation is maintained during aging. Endocrinology 2014 Jul, en20141223.
12. Berglund E.D., Liu C., Sohn J.W., Liu T., Kim M.H., Lee C.E., et al. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. Journal of Clinical Investigation 2013 Nov.
13. Bumaschny V.F., Yamashita M., Casas-Cordero R., Otero-Corchón V., de Souza F.S., Rubinstein M., et al. Obesity-programmed mice are rescued by early genetic intervention. Journal of Clinical Investigation 2012 Nov, 122(11):4203-4212.
14. Garfield A.S., Patterson C., Skora S., Gribble F.M., Reimann F., Evans M.L., et al. Neurochemical characterization of body weight-regulating leptin receptor neurons in the nucleus of the solitary tract. Endocrinology 2012 Oct, 153(10):4600-4607.
15. Lam D.D., Leinninger G.M., Louis G.W., Garfield A.S., Marston O.J., Leshan R.L., et al. Leptin does not directly affect CNS serotonin neurons to influence appetite. Cell Metabolism 2011 May, 13(5):584-591.
16. Paxinos G., Watson C. The rat brain - in stereotaxic coordinates - preface 1998, ix-+ p. 4th ed.
17. Leinninger G.M., Opland D.M., Jo Y.H., Faouzi M., Christensen L., Cappellucci L.A., et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metabolism 2011 Sep, 14(3):313-323.
18. Soliman G.A., Ishida-Takahashi R., Gong Y., Jones J.C., Leshan R.L., Saunders T.L., et al. A simple qPCR-based method to detect correct insertion of homologous targeting vectors in murine ES cells. Transgenic Research 2007 Oct, 16(5):665-670.
19. Martin C.K., Redman L.M., Zhang J., Sanchez M., Anderson C.M., Smith S.R., et al. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. Journal of Clinical Endocrinology and Metabolism 2011 Mar, 96(3):837-845.
20. Doslikova B., Garfield A.S., Shaw J., Evans M.L., Burdakov D., Billups B., et al. 5-HT2C receptor agonist anorectic efficacy potentiated by 5-HT1B receptor agonist coapplication: an effect mediated via increased proportion of pro-opiomelanocortin neurons activated. Journal of Neuroscience 2013 Jun, 33(23):9800-9804.
21. Harms M., Seale P. Brown and beige fat: development, function and therapeutic potential. Nature Medicine 2013 Oct, 19(10):1252-1263.
22. Virtue S., Vidal-Puig A. Assessment of brown adipose tissue function. Frontiers in Physiology 2013, 4:128.
23. Rossi J., Balthasar N., Olson D., Scott M., Berglund E., Lee C.E., et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metabolism 2011 Feb, 13(2):195-204.
24. Berglund E.D., Liu T., Kong X., Sohn J.W., Vong L., Deng Z., et al. Melanocortin 4 receptors in autonomic neurons regulate thermogenesis and glycemia. Nature Neuroscience 2014 Jul, 17(7):911-913.
25. Sohn J.W., Harris L.E., Berglund E.D., Liu T., Vong L., Lowell B.B., et al. Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell 2013 Jan, 152(3):612-619.
26. Elias C.F., Lee C., Kelly J., Aschkenasi C., Ahima R.S., Couceyro P.R., et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 1998 Dec, 21(6):1375-1385.
27. Swanson L.W., Kuypers H.G. A direct projection from the ventromedial nucleus and retrochiasmatic area of the hypothalamus to the medulla and spinal cord of the rat. Neuroscience Letters 1980 May, 17(3):307-312.
28. Bamshad M., Song C.K., Bartness T.J. CNS origins of the sympathetic nervous system outflow to brown adipose tissue. American Journal of Physiology 1999 Jun, 276(6 Pt 2):R1569-R1578.
29. Rothwell N.J., Stock M.J. Effect of diet and fenfluramine on thermogenesis in the rat: possible involvement of serotonergic mechanisms. International Journal of Obesity 1987, 11(4):319-324.
30. Lowell B.B., Flier J.S. Brown adipose tissue, beta 3-adrenergic receptors, and obesity. Annual Review of Medicine 1997, 48:307-316.
31. Chhabra K.H., Adams J.M., Fagel B., Lam D.D., Qi N., Rubinstein M., et al. Hypothalamic POMC-deficiency improves glucose tolerance despite insulin resistance by increasing glycosuria. Diabetes 2015 Oct.
32. Lam D.D., Attard C.A., Mercer A.J., Myers M.G., Rubinstein M., Low M.J. Conditional expression of Pomc in the Lepr-positive subpopulation of POMC neurons is sufficient for normal energy homeostasis and metabolism. Endocrinology 2015 Apr, 156(4):1292-1302.
33. Xu Y., Nedungadi T.P., Zhu L., Sobhani N., Irani B.G., Davis K.E., et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metabolism 2011 Oct, 14(4):453-465.