The control of fatty acid composition of membrane phospholipids in the genetically obese (ob/ob) mouse

Abstract

The fatty acyl composition of membrane phospholipids of lean and obese mice was analysed by gas liquid chromatography. Alterations to the hepatic mitochondrial, microsomal and brown adipose tissue (BAT) mitochondrial phospholipid compositions were observed in obese mice, and involved reduced linoleic acid content, increased oleic acid content and increased polyunsaturated fatty acid components. Essential fatty acid desaturation was investigated as a possible mechanism for controlling membrane lipid composition. Hepatic Δ6-desaturase activity was primarily located in the mitochondrial fraction in mice. Both Δ6- and Δ5-desaturase activity were increased in the liver of obese mice. The increase in Δ6-desaturase activity did not occur until weaning. Restriction of food intake reduced but did not normalise the hepatic Δ6-desaturase activity of the obese mice. Both cold acclimation and tri-iodothyronine injection reduced hepatic Δ6-desaturase of obese mice to levels observed in lean mice. The elevated enzyme activity in the obese animals was maintained after the induction of hypothyroidism. Some changes in fatty acid desaturation could be related to membrane lipid compositional changes in obese mice. However, thyroid hormone treatment was only partially successful in normalising the hepatic mitochondrial phospholipid-fatty acyl composition. It was concluded that changes in desaturase activity could not be used to predict changes in membrane lipid composition. Activity of lysophosphatidylcholine (lysoPC) acyltransferase in obese mice exhibited normal substrate selectivity with regard to oleic and linoleic acids. In experimental conditions paralleling the triglyceride fatty acid composition of obese mice, hepatic microsomal lysoPC acyl-transferase from lean or obese mice incorporated increased levels of oleic acid and reduced levels of linoleic acid into phosphatidylcholine. Consequences of altered membrane lipid composition on membrane protein function were investigated. The Arrhenius break temperature of ATP-Pi exchange activity was increased in hepatic mitochondria of the obese mouse. This was interpreted to suggest that a protein component of the ATP-Pi exchange complex was sensitive to the membrane compositional changes. However, the Arrhenius characteristics of hepatic mitochondrial cytochrome oxidase and succinate-cytochrome C reductase were similar in lean and obese animals. BAT mitochondrial thermogenesis, assessed by the GDP binding assay, was similar in lean and obese mice housed at room temperature, or exposed to a cold environment for 1 hour. It was concluded that altered membrane lipid composition was not involved in the defective BAT mitochondrial thermogenesis of obese mice. (D68304/86)

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