Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency

Xinxia Zhu, Stephanie M. Krasnow, Quinn R. Roth-Carter, Peter R. Levasseur, Theodore P. Braun, Aaron J. Grossberg, Daniel L. Marks

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Animals exhibit a rapid and sustained anorexia when fed a diet that is deficient in a single indispensable amino acid (IAA). The chemosensor for IAA deficiency resides within the anterior piriform cortex (APC). Although the cellular and molecular mechanisms by which the APC detects IAA deficiency are well established, the efferent neural pathways that reduce feeding in response to an IAA-deficient diet remain to be fully characterized. In the present work, we investigated whether 1) central melanocortin signaling is involved in IAA deficiency-induced anorexia (IAADA) and 2) IAADA engages other key appetite-regulating neuronal populations in the hypothalamus. Rats and mice that consumed a valine-deficient diet (VDD) for 2-3 wk exhibited marked reductions in food intake, body weight, fat and lean body mass, body temperature, and white adipose tissue leptin gene expression, as well as a paradoxical increase in brown adipose tissue uncoupling protein-1 mRNA. Animals consuming the VDD had altered hypothalamic gene expression, typical of starvation. Pharmacological and genetic blockade of central melanocortin signaling failed to increase long-term food intake in this model. Chronic IAA deficiency was associated with a marked upregulation of corticotropin-releasing hormone expression in the lateral hypothalamus, particularly in the parasubthalamic nucleus, an area heavily innervated by efferent projections from the APC. Our observations indicate that the hypothalamic melanocortin system plays a minor role in acute, but not chronic, IAADA and suggest that the restraint on feeding is analogous to that observed after chronic dehydration.

Original languageEnglish (US)
Pages (from-to)E1446-E1458
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number12
StatePublished - Dec 15 2012


  • Corticotropin-releasing hormone
  • Essential amino acid
  • Parasubthalamic nucleus
  • Valine
  • Wmelanocortin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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