Journal article
Leptin's hunger-suppressing effects are mediated by the hypothalamic-pituitary-adrenocortical axis in rodents
Proceedings of the National Academy of Sciences - PNAS, Vol.116(27), pp.13670-13679
07/02/2019
DOI: 10.1073/pnas.1901795116
PMCID: PMC6613139
PMID: 31213533
Abstract
Leptin informs the brain about sufficiency of fuel stores. When insufficient, leptin levels fall, triggering compensatory increases in appetite. Falling leptin is first sensed by hypothalamic neurons, which then initiate adaptive responses. With regard to hunger, it is thought that leptin-sensing neurons work entirely via circuits within the central nervous system (CNS). Very unexpectedly, however, we now show this is not the case. Instead, stimulation of hunger requires an intervening endocrine step, namely activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Increased corticosterone then activates AgRP neurons to fully increase hunger. Importantly, this is true for 2 forms of low leptin-induced hunger, fasting and poorly controlled type 1 diabetes. Hypoglycemia, which also stimulates hunger by activating CNS neurons, albeit independently of leptin, similarly recruits and requires this pathway by which HPA axis activity stimulates AgRP neurons. Thus, HPA axis regulation of AgRP neurons is a previously underappreciated step in homeostatic regulation of hunger.
Details
- Title: Subtitle
- Leptin's hunger-suppressing effects are mediated by the hypothalamic-pituitary-adrenocortical axis in rodents
- Creators
- Rachel J Perry - Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520Jon M Resch - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215Amelia M Douglass - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215Joseph C Madara - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215Aviva Rabin-Court - Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520Hakan Kucukdereli - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215Chen Wu - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215Joongyu D Song - Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520Bradford B Lowell - Program in Neuroscience, Harvard Medical School, Boston, MA 02215Gerald I Shulman - Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.116(27), pp.13670-13679
- DOI
- 10.1073/pnas.1901795116
- PMID
- 31213533
- PMCID
- PMC6613139
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences; United States
- Grant note
- UL1 TR000142 / NCATS NIH HHS R01 DK096010 / NIDDK NIH HHS R01 DK089044 / NIDDK NIH HHS U24 DK059635 / NIDDK NIH HHS R01 DK113984 / NIDDK NIH HHS T32 DK007058 / NIDDK NIH HHS K99 HL144923 / NHLBI NIH HHS K99 CA215315 / NCI NIH HHS R00 CA215315 / NCI NIH HHS P30 DK057521 / NIDDK NIH HHS R01 DK111401 / NIDDK NIH HHS R01 DK075632 / NIDDK NIH HHS P30 DK046200 / NIDDK NIH HHS T32 DK101019 / NIDDK NIH HHS UL1 TR001863 / NCATS NIH HHS R01 NS087568 / NINDS NIH HHS
- Language
- English
- Date published
- 07/02/2019
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984065750402771
Metrics
37 Record Views