Hindbrain leptin stimulation induces anorexia and hyperthermia mediated by hindbrain melanocortin receptors

Karolina P. Skibicka, Harvey J. Grill

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Of the central nervous system receptors that could mediate the energy balance effects of leptin, those of the hypothalamic arcuate nucleus receive the greatest attention. Melanocortin receptors (MC-Rs) contribute to the feeding and energetic effects of hypothalamically delivered leptin. Energy balance effects of leptin are also mediated by extrahypothalamic neurons including the hindbrain nucleus tractus solitarius. Hindbrain leptin receptors play a role in leptin's anorectic effects, but their contribution to its energetic effects and their functional interaction with melanocortin systems within the hindbrain remains unexplored. Here rats implanted with telemetric devices for recording energetic/cardiovascular responses were examined to determine whether: 1) hindbrain (fourth ventricular) leptin receptor stimulation triggers energetic and cardiovascular effects, 2) these effects are altered by a 6-wk high-fat diet maintenance, and 3) hindbrain MC-Rs mediate the thermogenic, cardiovascular, and anorexic effects of hindbrain leptin delivery. Results show that hindbrain leptin receptor stimulation produced long-lasting (>6 h) increases in core temperature and heart rate and also decreased food intake and body weight. These responses were not altered by high-fat maintenance, in contrast to what has been reported for forebrain leptin delivery. Fourth ventricular pretreatment with MC-R antagonist SHU 9119 completely abolished the hyperthermia, anorexia, and body weight loss seen with hindbrain-directed leptin but had no effects of its own. These data highlight a role for hindbrain leptin receptors in the initiation of energetic and anorexic responses and show that MCRs are part of the downstream mediation of hindbrain leptin-induced energy balance effects, paralleling effects observed for hypothalamic leptin receptors.

Original languageEnglish (US)
Pages (from-to)1705-1711
Number of pages7
JournalEndocrinology
Volume150
Issue number4
DOIs
StatePublished - Apr 1 2009

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Melanocortin Receptors
Rhombencephalon
Anorexia
Leptin
Fever
Leptin Receptors
Receptor, Melanocortin, Type 3
Body Weight
Maintenance
Melanocortins
Appetite Depressants
Arcuate Nucleus of Hypothalamus
Solitary Nucleus
High Fat Diet
Prosencephalon
Weight Loss
Central Nervous System
Eating
Heart Rate
Fats

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

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abstract = "Of the central nervous system receptors that could mediate the energy balance effects of leptin, those of the hypothalamic arcuate nucleus receive the greatest attention. Melanocortin receptors (MC-Rs) contribute to the feeding and energetic effects of hypothalamically delivered leptin. Energy balance effects of leptin are also mediated by extrahypothalamic neurons including the hindbrain nucleus tractus solitarius. Hindbrain leptin receptors play a role in leptin's anorectic effects, but their contribution to its energetic effects and their functional interaction with melanocortin systems within the hindbrain remains unexplored. Here rats implanted with telemetric devices for recording energetic/cardiovascular responses were examined to determine whether: 1) hindbrain (fourth ventricular) leptin receptor stimulation triggers energetic and cardiovascular effects, 2) these effects are altered by a 6-wk high-fat diet maintenance, and 3) hindbrain MC-Rs mediate the thermogenic, cardiovascular, and anorexic effects of hindbrain leptin delivery. Results show that hindbrain leptin receptor stimulation produced long-lasting (>6 h) increases in core temperature and heart rate and also decreased food intake and body weight. These responses were not altered by high-fat maintenance, in contrast to what has been reported for forebrain leptin delivery. Fourth ventricular pretreatment with MC-R antagonist SHU 9119 completely abolished the hyperthermia, anorexia, and body weight loss seen with hindbrain-directed leptin but had no effects of its own. These data highlight a role for hindbrain leptin receptors in the initiation of energetic and anorexic responses and show that MCRs are part of the downstream mediation of hindbrain leptin-induced energy balance effects, paralleling effects observed for hypothalamic leptin receptors.",
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Hindbrain leptin stimulation induces anorexia and hyperthermia mediated by hindbrain melanocortin receptors. / Skibicka, Karolina P.; Grill, Harvey J.

In: Endocrinology, Vol. 150, No. 4, 01.04.2009, p. 1705-1711.

Research output: Contribution to journalArticle

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