Dysregulation of arcuate nucleus preproneuropeptide Y mRNA in diet-induced obese rats.

Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) produce metabolic and physiological effects that promote the development and maintenance of obesity. In turn, NPY metabolism in these neurons is inhibited by dopamine release. In this study, ARC prepro-NPY mRNA and ARC/median eminence (ME) dopamine turnover were assessed in chow-fed male Sprague-Dawley rats prone to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a high-energy (HE) diet. By in situ hybridization, DIO-prone rats had 39% more ARC NPY mRNA expression than DR-prone rats under chow-fed conditions. DIO-prone rat ARC/ME dopamine levels were 14% higher, but dopamine half-life was 176% longer and turnover was 59% less than DR-prone rats. Neither a 48-h fast nor 50% energy intake restriction for 5 days affected the already increased ARC NPY mRNA levels in DIO-prone rats. Both manipulations increased NPY expression to the level of DIO-prone rats in DR-prone rats by 23 and 35%, respectively. Finally, when fed HE diet for 2 wk, neither DIO- nor DR-prone rats altered their ARC NPY expression despite the development of obesity and hyperinsulinemia in DIO rats. Thus DIO-prone rats overexpress and fail to regulate ARC NPY mRNA to energy restriction or hyperinsulinemia. This dysregulation is possibly secondary to reduced inhibition because of defective ARC/ME dopamine turnover. Both may be important predisposing factors in the development of DIO.
AuthorsB E Levin, A A Dunn-Meynell
JournalThe American journal of physiology (Am J Physiol) Vol. 272 Issue 5 Pt 2 Pg. R1365-70 (May 1997) ISSN: 0002-9513 [Print] UNITED STATES
PMID9176325 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Neuropeptide Y
  • Protein Precursors
  • RNA, Messenger
  • preproneuropeptide Y
  • Dopamine
  • Norepinephrine
  • Animals
  • Arcuate Nucleus of Hypothalamus (physiopathology)
  • Dopamine (metabolism)
  • Energy Intake
  • Gene Expression
  • Male
  • Neuropeptide Y (genetics)
  • Norepinephrine (urine)
  • Obesity (etiology, genetics, physiopathology)
  • Protein Precursors (genetics)
  • RNA, Messenger (genetics)
  • Rats
  • Rats, Sprague-Dawley

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