Pantheric Acids A–C from a Poisonous Mushroom, <i>Amanita pantherina</i>, Promote Lipid Accumulation in Adipocytes

Abstract

<i>Amanita pantherina</i> is a poisonous mushroom that causes muscle cramps, insanity, and audiovisual disorders. As part of our systematic study on Korean mushrooms, a chemical investigation of <i>A. pantherina</i> fruiting bodies resulted in the isolation and structural identification of three new fatty acid derivatives, pantheric acids A-C (<b>1</b>-<b>3</b>), and a known compound, 1,10-dimethyl ester-2-decenedioic acid (<b>4</b>). Although 1,10-dimethyl ester-2-decenedioic acid (<b>4</b>) was previously reported as a synthetic product, it was structurally identified from a natural source for the first time. The structures of the new compounds were established by detailed analysis of 1D and 2D (¹H-¹H COSY, HSQC, and HMBC) NMR, HRMS, and LC/MS/MS data. The absolute configurations of compounds <b>1</b> and <b>2</b> were unambiguously determined by a recently developed method using competing enantioselective acylation coupled with LC/MS analysis. The isolated compounds (<b>1</b>-<b>4</b>) were evaluated for their effects on lipid accumulation during adipocyte maturation. Pantheric acids A-C (<b>1</b>-<b>3</b>) promoted the enlargement of lipid droplets in 3T3-L1 adipocytes and altered lipid metabolism by inducing lipogenesis and inhibiting lipolysis. Our findings provide experimental evidence suggesting the potential adverse effects of pantheric acids A-C from a poisonous mushroom on lipid metabolism.