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Soraphen, an inhibitor of the acetyl‐CoA carboxylase system, improves peripheral insulin sensitivity in mice fed a high‐fat diet
Author(s) -
Schreurs M.,
Van Dijk T. H.,
Gerding A.,
Havinga R.,
Reijngoud D.J.,
Kuipers F.
Publication year - 2009
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2009.01078.x
Subject(s) - acetyl coa carboxylase , lipogenesis , medicine , endocrinology , insulin resistance , pyruvate carboxylase , insulin , insulin sensitivity , fatty acid synthesis , obesity , metabolism , chemistry , biology , enzyme , biochemistry
Aim: 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 β‐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 β‐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.