Mitochondrial Dynamics in the Brain Are Associated With Feeding, Glucose Homeostasis, and Whole-Body Metabolism

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2020 Nov 26

PMID 33240218

Citations 11

Authors

Jessica L Haigh

Lauryn E New

Beatrice M Filippi

Affiliations

Soon will be listed here.

Abstract

The brain is responsible for maintaining whole-body energy homeostasis by changing energy input and availability. The hypothalamus and dorsal vagal complex (DVC) are the primary sites of metabolic control, able to sense both hormones and nutrients and adapt metabolism accordingly. The mitochondria respond to the level of nutrient availability by fusion or fission to maintain energy homeostasis; however, these processes can be disrupted by metabolic diseases including obesity and type II diabetes (T2D). Mitochondrial dynamics are crucial in the development and maintenance of obesity and T2D, playing a role in the control of glucose homeostasis and whole-body metabolism across neurons and glia in the hypothalamus and DVC.

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References

Bagnol D, Lu X, Kaelin C, Day H, Ollmann M, Gantz I . Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J Neurosci. 1999; 19(18):RC26. PMC: 6782481. View

Davies V, Hollins A, Piechota M, Yip W, Davies J, White K . Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. Hum Mol Genet. 2007; 16(11):1307-18. DOI: 10.1093/hmg/ddm079. View

Liu T, Kong D, Shah B, Ye C, Koda S, Saunders A . Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron. 2012; 73(3):511-22. PMC: 3278709. DOI: 10.1016/j.neuron.2011.11.027. View

Navale A, Paranjape A . Glucose transporters: physiological and pathological roles. Biophys Rev. 2017; 8(1):5-9. PMC: 5425736. DOI: 10.1007/s12551-015-0186-2. View

Martins de Brito O, Scorrano L . Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008; 456(7222):605-10. DOI: 10.1038/nature07534. View

Chan O, Zhu W, Ding Y, McCrimmon R, Sherwin R . Blockade of GABA(A) receptors in the ventromedial hypothalamus further stimulates glucagon and sympathoadrenal but not the hypothalamo-pituitary-adrenal response to hypoglycemia. Diabetes. 2006; 55(4):1080-7. DOI: 10.2337/diabetes.55.04.06.db05-0958. View

Cassidy-Stone A, Chipuk J, Ingerman E, Song C, Yoo C, Kuwana T . Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008; 14(2):193-204. PMC: 2267902. DOI: 10.1016/j.devcel.2007.11.019. View

Xue A, Wu Y, Zhu Z, Zhang F, Kemper K, Zheng Z . Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018; 9(1):2941. PMC: 6063971. DOI: 10.1038/s41467-018-04951-w. View

Serra D, Mera P, Malandrino M, Mir J, Herrero L . Mitochondrial fatty acid oxidation in obesity. Antioxid Redox Signal. 2012; 19(3):269-84. PMC: 3691913. DOI: 10.1089/ars.2012.4875. View

10.

Ibrahim N, Bosch M, Smart J, Qiu J, Rubinstein M, Ronnekleiv O . Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology. 2003; 144(4):1331-40. DOI: 10.1210/en.2002-221033. View

11.

Nuzzaci D, Cansell C, Lienard F, Nedelec E, Ben Fradj S, Castel J . Postprandial Hyperglycemia Stimulates Neuroglial Plasticity in Hypothalamic POMC Neurons after a Balanced Meal. Cell Rep. 2020; 30(9):3067-3078.e5. DOI: 10.1016/j.celrep.2020.02.029. View

12.

Williams E, Chang R, Strochlic D, Umans B, Lowell B, Liberles S . Sensory Neurons that Detect Stretch and Nutrients in the Digestive System. Cell. 2016; 166(1):209-21. PMC: 4930427. DOI: 10.1016/j.cell.2016.05.011. View

13.

Wan H, Hulsey M, Martin R . Intracerebroventricular administration of antisense oligodeoxynucleotide against GLUT2 glucose transporter mRNA reduces food intake, body weight change and glucoprivic feeding response in rats. J Nutr. 1998; 128(2):287-91. DOI: 10.1093/jn/128.2.287. View

14.

Roman C, Derkach V, Palmiter R . Genetically and functionally defined NTS to PBN brain circuits mediating anorexia. Nat Commun. 2016; 7:11905. PMC: 4912612. DOI: 10.1038/ncomms11905. View

15.

Ono H, Pocai A, Wang Y, Sakoda H, Asano T, Backer J . Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats. J Clin Invest. 2008; 118(8):2959-68. PMC: 2447927. DOI: 10.1172/JCI34277. View

16.

Fan X, Chan O, Ding Y, Zhu W, Mastaitis J, Sherwin R . Reduction in SGLT1 mRNA Expression in the Ventromedial Hypothalamus Improves the Counterregulatory Responses to Hypoglycemia in Recurrently Hypoglycemic and Diabetic Rats. Diabetes. 2015; 64(10):3564-72. PMC: 4587643. DOI: 10.2337/db15-0022. View

17.

Miki T, Liss B, Minami K, Shiuchi T, Saraya A, Kashima Y . ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci. 2001; 4(5):507-12. DOI: 10.1038/87455. View

18.

Leino R, Gerhart D, van Bueren A, McCall A, Drewes L . Ultrastructural localization of GLUT 1 and GLUT 3 glucose transporters in rat brain. J Neurosci Res. 1997; 49(5):617-26. DOI: 10.1002/(SICI)1097-4547(19970901)49:5<617::AID-JNR12>3.0.CO;2-S. View

19.

Wang R, Liu X, Hentges S, Dunn-Meynell A, Levin B, Wang W . The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. Diabetes. 2004; 53(8):1959-65. DOI: 10.2337/diabetes.53.8.1959. View

20.

Smith E, Shaw P, De Vos K . The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 2017; 710:132933. DOI: 10.1016/j.neulet.2017.06.052. View