Studies on the relationship between fatty acid biosynthesis and esterification in rat adipocytes

Henderson, Robert James (1977) Studies on the relationship between fatty acid biosynthesis and esterification in rat adipocytes. PhD thesis, University of Glasgow.

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This thesis describes studies in which rat adipocytes, prepared by collagenase digestion of parametrial adipose tissue, were used to examine the relationship between the synthesis of fatty acids and their subsequent esterification into triacylglycerols. The introductory chapter reviews the literature available to date concerning fatty acid and triacylglycerol biosynthesis in adipose tissue, and discusses the control of each separately. It is noted that although lipogenesis in adipose tissue has been studied extensively, its relationship to the synthesis of the final product, triacylglycerols, is poorly understood particularly with respect to any effect on the esterification of fatty acids into particular positions of the triacylglycerol molecule. Studies have therefore been made of the manner in which fatty acids of exogenous origin were utilised for triacylglycerol biosynthesis by the adipocyte in vitro in comparison to fatty acids synthesized de novo by the cell from low molecular weight precursors or by modification of preformed fatty acids. A comparison was made between the rates of esterification of fatty acids supplied to the adipocytes individually or as components of a fatty acid mixture of a composition similar to that likely to be available to the cell. Whilst most of the fatty acids in each instance were taken up and esterified into triacylglycerols, a significant proportion were recovered in diacylglycerols having a slow rate of conversion to triacylglycerols. No differences in the rates of esterification into acylglycerols were obvious between palmitic, stearic, oleic and linoleic acids when supplied individually but oleic acid had the highest rate of esterification into triacylglycerols when the same fatty acids were incubated as a mixture. Using a stereo-specific analysis procedure, the positional distribution of esterified extracellular fatty acids in triacylglycerols was shown to differ from the natural distribution of fatty acids in rat adipocyte triacyl-glycerols and oleic acid formed by the desaturation of exogenous stearic acid was located predominantly in position sn-5. Tripalmitoyl-glycerol was found to be synthesized by adipocytes incubated with palmitic acid on its own at a high concentration. The rate of desaturation of stearic acid was greater when the stearic acid substrate was supplied to the fat-cells alone than in the presence of other fatty acids, and in both instances the oleic acid product was rapidly esterified into acylglycerols, predominantly triacylglycerols. Experiments on fatty acid synthesis de novo from acetate or glucose showed that the rate of fatty acid synthesis decreased with the age of the rat from which the adipocytes were prepared. Preparative G.L.C. with subsequent measurement of radioactivity was used to study the fatty acids synthesized from 14C-labelled acetate or glucose and esterified into triacyl- and diacylglycerols. The pattern of fatty acids formed from acetate was found to be dependent on age, with a higher proportion of oleic acid being formed by adipocytes isolated from young rats. The effect of exogenous fatty acids on the synthesis and esterification of endogenous fatty acids was studied by incubating adipocytes simultaneously with a mixture of fatty acids and either 14C-labelled acetate or glucose, or tritiated water. Whereas the ncorporation of acetate and 3H2O into fatty acids was decreased in the presence of extracellular fatty acids, fatty acid synthesis from glucose was not inhibited. The pattern of triacylglycerol fatty acids formed from acetate was influenced by the presence of fatty acids in the incubation medium, under which circumstances the proportion of newly-synthesized fatty acids incorporated into position sn-3 of triacyl-sn-glycerols decreased. In all experiments, diacylglycerol was the only intermediate in the sn-glycerol 3-phosphate pathway that tended to accumulate, and in particular with adipocytes from mature rats an accumulation in diacyl-glycerols of fatty acids newly-synthesized from acetate was observed at high acetate concentrations. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: W W Christie
Keywords: Physiology
Date of Award: 1977
Depositing User: Enlighten Team
Unique ID: glathesis:1977-73133
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56

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