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. 1990 Jan;85(1):291–295. doi: 10.1172/JCI114425

Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.

P Valet 1, M Berlan 1, M Beauville 1, F Crampes 1, J L Montastruc 1, M Lafontan 1
PMCID: PMC296417  PMID: 2104880

Abstract

Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells.

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Selected References

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  1. Adrian T. E., Ferri G. L., Bacarese-Hamilton A. J., Fuessl H. S., Polak J. M., Bloom S. R. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology. 1985 Nov;89(5):1070–1077. doi: 10.1016/0016-5085(85)90211-2. [DOI] [PubMed] [Google Scholar]
  2. Berlan M., Lafontan M. Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha 2 adrenoceptor properties. Eur J Clin Invest. 1985 Dec;15(6):341–348. doi: 10.1111/j.1365-2362.1985.tb00282.x. [DOI] [PubMed] [Google Scholar]
  3. Cannon B., Nedergaard J., Lundberg J. M., Hökfelt T., Terenius L., Goldstein M. 'Neuropeptide tyrosine' (NPY) is co-stored with noradrenaline in vascular but not in parenchymal sympathetic nerves of brown adipose tissue. Exp Cell Res. 1986 Jun;164(2):546–550. doi: 10.1016/0014-4827(86)90052-2. [DOI] [PubMed] [Google Scholar]
  4. DOLE V. P., MEINERTZ H. Microdetermination of long-chain fatty acids in plasma and tissues. J Biol Chem. 1960 Sep;235:2595–2599. [PubMed] [Google Scholar]
  5. Fain J. N., Garcĩa-Sáinz J. A. Adrenergic regulation of adipocyte metabolism. J Lipid Res. 1983 Aug;24(8):945–966. [PubMed] [Google Scholar]
  6. Galitzky J., Mauriege P., Berlan M., Lafontan M. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists. J Pharmacol Exp Ther. 1989 May;249(2):583–591. [PubMed] [Google Scholar]
  7. Glover I. D., Barlow D. J., Pitts J. E., Wood S. P., Tickle I. J., Blundell T. L., Tatemoto K., Kimmel J. R., Wollmer A., Strassburger W. Conformational studies on the pancreatic polypeptide hormone family. Eur J Biochem. 1984 Jul 16;142(2):379–385. doi: 10.1111/j.1432-1033.1984.tb08298.x. [DOI] [PubMed] [Google Scholar]
  8. Kassis S., Olasmaa M., Terenius L., Fishman P. H. Neuropeptide Y inhibits cardiac adenylate cyclase through a pertussis toxin-sensitive G protein. J Biol Chem. 1987 Mar 15;262(8):3429–3431. [PubMed] [Google Scholar]
  9. Kather H., Schröder F., Simon B. Microdetermination of glycerol using bacterial NADH-linked luciferase. Clin Chim Acta. 1982 Apr 23;120(3):295–300. doi: 10.1016/0009-8981(82)90370-9. [DOI] [PubMed] [Google Scholar]
  10. Lluis F., Thompson J. C. Neuroendocrine potential of the colon and rectum. Gastroenterology. 1988 Mar;94(3):832–844. doi: 10.1016/0016-5085(88)90262-4. [DOI] [PubMed] [Google Scholar]
  11. Mauriege P., Galitzky J., Berlan M., Lafontan M. Heterogeneous distribution of beta and alpha-2 adrenoceptor binding sites in human fat cells from various fat deposits: functional consequences. Eur J Clin Invest. 1987 Apr;17(2):156–165. doi: 10.1111/j.1365-2362.1987.tb02395.x. [DOI] [PubMed] [Google Scholar]
  12. Murayama T., Ui M. Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J Biol Chem. 1983 Mar 10;258(5):3319–3326. [PubMed] [Google Scholar]
  13. Pappas T. N., Debas H. T., Goto Y., Taylor I. L. Peptide YY inhibits meal-stimulated pancreatic and gastric secretion. Am J Physiol. 1985 Jan;248(1 Pt 1):G118–G123. doi: 10.1152/ajpgi.1985.248.1.G118. [DOI] [PubMed] [Google Scholar]
  14. Potter E. K. Neuropeptide Y as an autonomic neurotransmitter. Pharmacol Ther. 1988;37(2):251–273. doi: 10.1016/0163-7258(88)90028-9. [DOI] [PubMed] [Google Scholar]
  15. RODBELL M. METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. J Biol Chem. 1964 Feb;239:375–380. [PubMed] [Google Scholar]
  16. Rouot B., Carrette J., Lafontan M., Lan Tran P., Fehrentz J. A., Bockaert J., Toutant M. The adipocyte Go alpha-immunoreactive polypeptide is different from the alpha subunit of the brain Go protein. Biochem J. 1989 May 15;260(1):307–310. doi: 10.1042/bj2600307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Servin A. L., Rouyer-Fessard C., Balasubramaniam A., Saint Pierre S., Laburthe M. Peptide-YY and neuropeptide-Y inhibit vasoactive intestinal peptide-stimulated adenosine 3',5'-monophosphate production in rat small intestine: structural requirements of peptides for interacting with peptide-YY-preferring receptors. Endocrinology. 1989 Feb;124(2):692–700. doi: 10.1210/endo-124-2-692. [DOI] [PubMed] [Google Scholar]
  18. Taouis M., Berlan M., Montastruc P., Lafontan M. Characterization of dog fat cell adrenoceptors: variations in alpha-2 and beta adrenergic receptors distribution according to the extent of the fat deposits and the anatomical location. J Pharmacol Exp Ther. 1987 Sep;242(3):1041–1049. [PubMed] [Google Scholar]
  19. Valet P., Montastruc J. L., Berlan M., Tran M. A., Lafontan M., Montastruc P. Differential regulation of fat cell beta-2 and beta-1 adrenoceptors by endogenous catecholamines in dog. J Pharmacol Exp Ther. 1989 Apr;249(1):271–277. [PubMed] [Google Scholar]
  20. Whitehead T. P., Kricka L. J., Carter T. J., Thorpe G. H. Analytical luminescence: its potential in the clinical laboratory. Clin Chem. 1979 Sep;25(9):1531–1546. [PubMed] [Google Scholar]
  21. Zukowska-Grojec Z., Konarska M., McCarty R. Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats. Life Sci. 1988;42(17):1615–1624. doi: 10.1016/0024-3205(88)90440-7. [DOI] [PubMed] [Google Scholar]

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