Journal article
Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus
Diabetes (New York, N.Y.), Vol.64(6), pp.1976-1987
06/2015
DOI: 10.2337/db14-1257
PMCID: PMC4439564
PMID: 25605803
Abstract
Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4R(LHA) signaling regulates glucose tolerance and sympathetic nerve activity. Restoring expression of MC4Rs specifically in the LHA improves glucose intolerance in obese MC4R-null mice without affecting body weight or circulating insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake identifies the interscapular brown adipose tissue (iBAT) as a primary source where glucose uptake is increased in MC4R(LHA) mice. Direct multifiber sympathetic nerve recording further reveals that sympathetic traffic to iBAT is significantly increased in MC4R(LHA) mice, which accompanies a significant elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation prevents the glucoregulatory effect of MC4R(LHA) signaling. These results identify a novel role for MC4R(LHA) signaling in the control of sympathetic nerve activity and glucose tolerance independent of energy balance.
Details
- Title: Subtitle
- Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the lateral hypothalamus
- Creators
- Donald A Morgan - Department of Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IALatisha N McDaniel - Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IATerry Yin - Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IAMichael Khan - Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IAJingwei Jiang - Department of Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IAMichael R Acevedo - Small Animal Imaging Core, University of Iowa, Carver College of Medicine, Iowa City, IASusan A Walsh - Small Animal Imaging Core, University of Iowa, Carver College of Medicine, Iowa City, IALaura L Boles Ponto - Department of Radiology, University of Iowa, Carver College of Medicine, Iowa City, IA Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IAAndrew W Norris - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IAMichael Lutter - Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Carver College of Medicine, Iowa City, IA Obesity Research and Education Initiative, University of Iowa, Carver College of Medicine, Iowa City, IAKamal Rahmouni - Department of Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IA Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Carver College of Medicine, Iowa City, IA Obesity Research and Education Initiative, University of Iowa, Carver College of Medicine, Iowa City, IAHuxing Cui - Department of Pharmacology, University of Iowa, Carver College of Medicine, Iowa City, IA Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Carver College of Medicine, Iowa City, IA huxing-cui@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.64(6), pp.1976-1987
- Publisher
- United States
- DOI
- 10.2337/db14-1257
- PMID
- 25605803
- PMCID
- PMC4439564
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- MH-084058-01A1 / NIMH NIH HHS K08 MH084058 / NIMH NIH HHS R01 DK097820 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS HL-084207 / NHLBI NIH HHS (01-DK-097820 / NIDDK NIH HHS
- Language
- English
- Date published
- 06/2015
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Endocrinology and Diabetes; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984025295402771
Metrics
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