Caralluma fimbriata extract activity involves the 5-HT2c receptor in PWS Snord116 deletion mouse model

Brain Behav. 2018 Dec;8(12):e01102. doi: 10.1002/brb3.1102. Epub 2018 Oct 23.

Abstract

Introduction: In Prader-Willi syndrome (PWS), nonprotein coding small nucleolar (sno) RNAs are involved in the paternally deleted region of chromosome 15q11.2-q13, which is believed to cause the hyperphagic phenotype of PWS. Central to this is SnoRNA116. The supplement Caralluma fimbriata extract (CFE) has been shown to decrease appetite behavior in some individuals with PWS. We therefore investigated the mechanism underpinning the effect of CFE on food intake in the Snord116del mouse. Experiments utilized appetite stimulants which included a 5-hydroxytryptamine (5-HT) 2c receptor antagonist (SB242084), as the 5-HT2cR is implicated in central signaling of satiety.

Methods: After 9-week chronic CFE treatment (33 mg or 100 mg kg-1 day-1 ) or placebo, the 14-week-old Snord116del (SNO) and wild-type mice (n = 72) were rotated through intraperitoneal injections of (a) isotonic saline; (b) 400 mg/kg of 2-deoxyglucose (2DG) (glucose deprivation); (c) 100 mglkg beta-mercaptoacetate (MA), fatty acid signaling; and (d) SB242084 (a selective 5HT2cR antagonist), with 5 days between reagents. Assessments of food intake were from baseline to 4 hr, followed by immunohistochemistry of neural activity utilizing c-Fos, neuropeptide Y, and alpha-melanocyte-stimulating hormone within hypothalamic appetite pathways.

Results: Caralluma fimbriata extract administration decreased food intake more strongly in the SNO100CFE group with significantly stimulated food intake demonstrated during coadministration with SB242084. Though stimulatory deprivation was expected to stimulate food intake, 2DG and MA resulted in lower intake in the snord116del mice compared to the WT animals (p = <0.001). Immunohistochemical mapping of hypothalamic neural activity was consistent with the behavioral studies.

Conclusions: This study identifies a role for the 5-HT2cR in CFE-induced appetite suppression and significant stimulatory feeding disruptions in the snord116del mouse model.

Keywords: 5-HT2c receptor; Caralluma Fimbriata extract; Prader-Willi syndrome (PWS); appetite signaling; cactus supplement; snord116 deletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Apocynaceae*
  • Appetite Depressants / pharmacology
  • Chromosome Deletion
  • Disease Models, Animal
  • Eating / drug effects
  • Female
  • Gene Deletion
  • Humans
  • Hypothalamus / metabolism
  • Indoles / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Phenotype
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Prader-Willi Syndrome / drug therapy*
  • RNA, Small Nucleolar / genetics
  • Random Allocation
  • Receptor, Serotonin, 5-HT2C / drug effects*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology

Substances

  • 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
  • Aminopyridines
  • Appetite Depressants
  • Indoles
  • Plant Extracts
  • RNA, Small Nucleolar
  • Receptor, Serotonin, 5-HT2C
  • SNORD116 RNA, mouse
  • Serotonin 5-HT2 Receptor Antagonists