An approach toward CNS dysfunction associated with metabolic syndrome; Implication of leptin, which is a key molecule of obesity, in depression associated with obesity

Nobuko Goto, Goro Katsuura, Yukari Ochi, Kazuwa Nakao

Research output: Contribution to journalArticle

2 Citations (Scopus)


Obesity is the most critical factor in the pathology of metabolic syndrome (MetS), and is associated with an increased risk of depression. The imbalance of hormones and neural peptides which are involved in energy regulation are observed in obesity. It becomes evident that these hormones and neural peptides also affect mood. Leptin plays a pivotal role in energy regulation mainly acting in the hypothalamus of the brain. Although obese humans and rodents usually have high circulating levels of leptin, leptin neither reduces food intake nor increases energy expenditure. This paradoxical situation in obesity has been termed "leptin resistance", which is considered to be a central dogma for obesity. Based on these observations, we examined the functional significance of leptin in the regulation of the depressive state in diet-induced obese (DIO) mice. Our recent study demonstrated that DIO mice showed severe depressive behavior without response to the antidepressant effect of leptin, which is, in part, due to the impairment of leptin action in the hippocampus (Yamada, et al., Endocrinology, 2011). MetS and CNS dysfunction might have common pathological bases vulnerable to these disorders. Our future direction is to investigate a new treatment strategy of MetS by analyzing CNS dysfunction associated with obesity.

Original languageEnglish
Pages (from-to)245-250
Number of pages6
JournalJapanese Journal of Neuropsychopharmacology
Issue number5-6
Publication statusPublished - 2012 Nov 1
Externally publishedYes



  • CNS dysfunction
  • Depression
  • Leptin resistance
  • Metabolic syndrome
  • Obesity

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology
  • Pharmacology (medical)
  • Pharmacology

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