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A study on the role of the molecular organisation of cell membranes in the development of obesity

A study on the role of the molecular organisation of cell membranes in the development of obesity
A study on the role of the molecular organisation of cell membranes in the development of obesity

The molecular organisation of the adipocyte plasma membrane from lean and genetically obese (ob/ob) mice has been investigated. No difference was detected in the protein or cholesterol to phospholipid ratio between the membranes from the two phenotypes. The location of phospholipid classes in the two halves of the membrane bilayer has been determined for the adipocyte plasma membrane, and again no difference was apparent in either the phospholipid composition or the asymmetric arrangement of these phospholipid classes between the membranes from both phenotypes. Using fluorescence depolarisation by probe labelled membranes, the fluidity of obese mouse adipocyte plasma membranes was found to be greatly increased compared to loan controls. The fluidity difference was largely due to an increase in long chain polyunsaturated fatty acids esterified to carbon atom 2 of phosphatidylethanolamine (PE). This phospholipid is confined to the inner half of the bilayer. The major fatty acid responsible for the fluidity change in obese mouse membranes is docosahexaenoic acid. Evidence is presented that the presence of thin fatty acid in membranes regulates a number of metabolic processes, particularly the hormonal stimulation of adenylate cyclase. This concept is extended to form a general hypothesis that the presence of increased docosahexaenoyl PE in membranes forms the basis of many of the observed metabolic changes in the obese condition. As obesity is a disorder of energy balance, the locus of the regulation of cellular metabolic efficiency is postulated to reside at the level or the phospholipid composition of the plasma membrane.

University of Southampton
Hyslop, Paul Andrew
96bb2d37-ddcb-463d-85e7-47fec2001dc7
Hyslop, Paul Andrew
96bb2d37-ddcb-463d-85e7-47fec2001dc7
York, David
e5ba1de7-50b5-44ab-ad1b-485706ec369a

Hyslop, Paul Andrew (1981) A study on the role of the molecular organisation of cell membranes in the development of obesity. University of Southampton, Doctoral Thesis, 324pp.

Record type: Thesis (Doctoral)

Abstract

The molecular organisation of the adipocyte plasma membrane from lean and genetically obese (ob/ob) mice has been investigated. No difference was detected in the protein or cholesterol to phospholipid ratio between the membranes from the two phenotypes. The location of phospholipid classes in the two halves of the membrane bilayer has been determined for the adipocyte plasma membrane, and again no difference was apparent in either the phospholipid composition or the asymmetric arrangement of these phospholipid classes between the membranes from both phenotypes. Using fluorescence depolarisation by probe labelled membranes, the fluidity of obese mouse adipocyte plasma membranes was found to be greatly increased compared to loan controls. The fluidity difference was largely due to an increase in long chain polyunsaturated fatty acids esterified to carbon atom 2 of phosphatidylethanolamine (PE). This phospholipid is confined to the inner half of the bilayer. The major fatty acid responsible for the fluidity change in obese mouse membranes is docosahexaenoic acid. Evidence is presented that the presence of thin fatty acid in membranes regulates a number of metabolic processes, particularly the hormonal stimulation of adenylate cyclase. This concept is extended to form a general hypothesis that the presence of increased docosahexaenoyl PE in membranes forms the basis of many of the observed metabolic changes in the obese condition. As obesity is a disorder of energy balance, the locus of the regulation of cellular metabolic efficiency is postulated to reside at the level or the phospholipid composition of the plasma membrane.

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81169643 - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: 1981

Identifiers

Local EPrints ID: 459589
URI: http://eprints.soton.ac.uk/id/eprint/459589
PURE UUID: 37cd1e01-67c3-467b-8c80-b4570fe01529

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Date deposited: 04 Jul 2022 17:14
Last modified: 16 Mar 2024 18:31

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Contributors

Author: Paul Andrew Hyslop
Thesis advisor: David York

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