Neuroendocrinology of insulin resistance: metabolic and endocrine aspects of adiposity

G van Dijk*, K de Vries, L Benthem, C Nyakas, B Buwalda, AJW Scheurink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)
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Abstract

Abdominal obesity is a major risk factor to attract the insulin resistance syndrome. It is proposed that abdominal obesity exposes the liver to elevated levels of free fatty acids, which activate a neuroendocrine reflex, leading to increased circulating levels of glucocorticoids. Besides directly attenuating peripheral insulin signaling, glucocorticoids oppose the activity of central nervous regulatory systems that stimulate insulin action. Among the factors that promote insulin action is leptin. Leptin regulates peripheral fuel partitioning and insulin action mainly through hypothalamic neuronal networks, which in turn, regulate endocrine activity of adipose tissue in a way comparable to thiazolidinediones. These are a class of insulin-sensitizing drugs, which exert their antidiabetic effects through the gamma isoform of peroxisome proliferator-activated receptor (PPAR-gamma). Since glucocorticoids oppose leptin action at several levels of control (including the central nervous system, CNS), it is argued that subjects easily develop obesity and associated metabolic disorders. (C) 2003 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)31-42
Number of pages12
JournalEuropean Journal of Pharmacology
Volume480
Issue number1-3
DOIs
Publication statusPublished - 7-Nov-2003
Event3rd EJP Spring Meeting on Drug Targets for Psychiatric Disorders - , Netherlands
Duration: 13-Jun-200316-Jun-2003

Keywords

  • fatty acid
  • glucocorticoid
  • leptin
  • adiponectin
  • PPARy (peroxisome proliferator-activated receptor)
  • hypothalamus
  • MELANIN-CONCENTRATING HORMONE
  • COMPLEMENT-RELATED PROTEIN
  • STEAROYL-COA DESATURASE-1
  • OBESE ZUCKER RATS
  • CHAIN FATTY-ACIDS
  • NEUROPEPTIDE-Y
  • MELANOCORTIN RECEPTORS
  • PPAR-GAMMA
  • SYMPATHETIC ACTIVATION
  • GLUCOSE-UTILIZATION

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