Inhibition of hypothalamic neuropeptide Y gene expression by insulin.
Abstract
Insulin acts in the brain to suppress feeding, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting lowers plasma insulin levels and increases hypothalamic synthesis of NPY, we proposed that insulin may inhibit hypothalamic NPY gene expression. To test this hypothesis, we used RIA and in situ hybridization histochemistry to determine if centrally administered insulin could reduce levels of both NPY and its messenger RNA (mRNA) in discreet hypothalamic regions during fasting. Three groups of Long-Evans rats were entered into a 72-h study protocol. One group was fed ad libitum during this period, while the others were fasted. Fed rats received intracerebroventricular (icv) injections of saline vehicle at 12-h intervals, whereas fasted groups received icv vehicle alone or with insulin (4 mU/12 h). In vehicle-only treated rats, fasting significantly increased expression of preproNPY mRNA in the arcuate nucleus to 179 +/- 20% of fed controls. Administration of icv insulin during fasting abolished this increase (99 +/- 14% of fed controls; P less than 0.05 vs. fasted, vehicle-treated rats). Central insulin administration during fasting also reduced immunoreactive NPY concentrations in samples punched from the paraventricular nucleus (PVN) (875 +/- 122 pg/punch) to levels below vehicle-only treated rats (1396 +/- 435 pg/punch; P less than 0.05), similar to free-feeding control values (814 +/- 170 pg/punch). By comparison, neither fasting nor central insulin administration altered NPY levels in four other hypothalamic regions (supraoptic, ventromedial, dorsomedial, and arcuate nuclei). Continuous icv insulin infusion at a lower dose (2 mU/day) produced a similar result during a shorter period (48 h) of food deprivation in Wistar rats. In this study, central insulin infusion also inhibited the fasting-related increase in arcuate preproNPY mRNA levels and did not affect plasma glucose or insulin levels. This suggests that insulin acts locally to inhibit hypothalamic NPY mRNA expression. We conclude that the increase of levels of NPY in the PVN and preproNPY mRNA in the arcuate nucleus during fasting are inhibited by icv insulin. Fasting, therefore, increases NPY biosynthesis along an arcuate nucleus-PVN pathway in the hypothalamus via a mechanism dependent on low insulin levels.
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Insulin inhibits NPY expression in AgRP/NPY neurons, which are known to secrete the orexigenic neuropeptides NPY and AgRP.
“In contrast to its pro-opiomelanocortin-stimulating action, insulin inhibits NPY expression144 in Agouti-related peptide (AgRP/NPY) neurons, which are known to secrete the orexigenic neuropeptides NPY145, 146, 147 and AgRP.148, 149”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [144]
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- Authors
- Schwartz, M. W., Sipols, A. J., Marks, J. L., Sanacora, G., White, J. D., Scheurink, A., Kahn, S. E., Baskin, D. G., Woods, S. C., & Figlewicz, D. P.
- Affiliations
- University of Washington (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1992-06
- Volume
- 130
- Issue
- 6
- Pages
- 3608-3616
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2088777766
- Cited by
- 555
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 12 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 7 · 2016: 17 · 2015: 15 · 2014: 17 · 2013: 23 · 2012: 25
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Institutes of Health (2r01dk012829-36)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, DK17844, DK-17047, P30DK017047)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- neuropeptide Y, insulin, hypothalamus, fasting, arcuate nucleus, paraventricular nucleus, food intake regulation, feeding inhibition, rats, Wistar rats, Long-Evans rats, food deprivation, plasma glucose, plasma insulin
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Cerebral Ventricles, Eating, Fasting, Hypothalamus, Injections, Intraventricular, Insulin, Male, Neuropeptide Y, Organ Specificity, Protein Precursors, RNA, Messenger, Gene Expression, Rats
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