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Soraphen, an inhibitor of the acetyl-CoA carboxylase system, improves peripheral insulin sensitivity in mice fed a high-fat diet.

AbstractAIM:
Inhibition of the acetyl-CoA carboxylase (ACC) system, consisting of the isozymes ACC1 and ACC2, may be beneficial for treatment of insulin resistance and/or obesity by interfering with de novo lipogenesis and beta-oxidation. We have evaluated effects of pharmacological inhibition of ACC by soraphen (SP) on high fat (HF) diet-induced insulin resistance in mice.
METHOD:
Male C57Bl6/J mice were fed control chow, a HF diet or a HF diet supplemented with SP (50 or 100 mg/kg/day).
RESULTS:
Body weight gain and total body fat content of SP-treated animals were significantly reduced compared with HF-fed mice. Fractional synthesis of palmitate was significantly reduced in mice treated with SP, indicative for ACC1 inhibition. Plasma beta-hydroxybutyrate levels were significantly elevated by SP, reflecting simultaneous inhibition of ACC2 activity. Mice treated with SP showed improved peripheral insulin sensitivity, as assessed by hyperinsulinaemic euglycaemic clamps.
CONCLUSION:
Pharmacological inhibition of the ACC system is of potential use for treatment of key components of the metabolic syndrome.
AuthorsM Schreurs, T H van Dijk, A Gerding, R Havinga, D-J Reijngoud, F Kuipers
JournalDiabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 11 Issue 10 Pg. 987-91 (Oct 2009) ISSN: 1463-1326 [Electronic] England
PMID19519866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dietary Fats
  • Insulin
  • Macrolides
  • RNA, Mitochondrial
  • soraphen A
  • Palmitic Acid
  • RNA
  • Cholesterol
  • Acetyl-CoA Carboxylase
  • 3-Hydroxybutyric Acid
Topics
  • 3-Hydroxybutyric Acid (blood)
  • Acetyl-CoA Carboxylase (antagonists & inhibitors)
  • Animals
  • Cholesterol (metabolism)
  • Diet
  • Dietary Fats (administration & dosage)
  • Glucose Clamp Technique
  • Insulin (metabolism)
  • Insulin Resistance (physiology)
  • Liver (metabolism)
  • Macrolides (pharmacology)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Obesity (metabolism, physiopathology)
  • Palmitic Acid (metabolism)
  • Polymerase Chain Reaction (methods)
  • RNA (metabolism)
  • RNA, Mitochondrial
  • Weight Gain (drug effects)

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