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Medicine

Lipid Biology

Lipids are a heterogeneous group of hydrophobic molecules with a wide range of biological functions including structural roles in cell membranes, triacylglycerol storage in adipocytes and acting as signalling molecules.  Lipid composition is a major determinant of membrane protein activitiy and active synthesis of phospholipid is critically important for successful cell division.

In Medicine, we are studying the consequences of failure to acquire or maintain cell type-specific membrane lipid compositions, though sub-optimal development, disease or inadequate nutrition, on post-natal development of preterm infants, immune cell functions, inflammatory processes, and alcoholic and non-alcoholic fatty liver disease.  There are two major groups in the Faculty with complementary facilities for lipid analyses, based in Human Development and Health (Professor Philip Calder, PI) and Inflammation, Infection & Immunity (Professor Tony Postle, PI).  The Calder group employs gas chromatography (GC) to analyse fatty acids in samples representing the transport, structural and functional pools of fatty acids. The Postle group uses a range of electrospray ionisation-FMS methodologies to quantify compositions, rates of synthesis, hydrolysis and oxidation, and concentrations of intact individual molecular species of lipids.  These activities are co-ordinated through the Southampton Centre for Biomedical Research (SCBR) MS Unit and support a large number of collaborative projects within the faculty, across the University and externally.  They form one of the core contributors to the Lipid Biology research theme of the Institute for Life Sciences at the University of Southampton.

Current research projects within the Lipid Biology theme in the Faculty of Medicine are outlined below.

Synthesis and turnover of lung surfactant phospholipids in preterm infants, children and adults with respiratory failure, using incorporation of stable isotope labelled D9choline into phosphatidylcholine (PC)
Professors Tony Postle , Howard Clark & Mike Grocott, Dr John Pappachan See Figure 1.

Postnatal lipid nutrition and immune cell function, investigating the effects of intravenous feeding on neutrophil functions and defence mechanisms against infection
Professors Tony Postle & Howard Clark , Dr Alison Leaf

High accuracy Fourier-transformed Ion Cyclotron Resonance (FT-ICR) MS for characterisation of lipid oxidation :

Macrophage phospholipid metabolism in Crohn's disease
Professor Tony Postle

Peritoneal fluid lipids, mesothelial cells and wound healing
Miss Ying Cheong & Professor Tony Postle

Phospholipase activities of snake neurotoxins
Professor Tony Postle

Bioavailability and biodisposition of omega-3 fatty acids consumed in different chemical forms
Professor Philip Calder & Dr Graham Burdge

Influence of omega-3 fatty acids on post-prandial and chronic low grade inflammatory processes in lean and obese humans
Professor Philip Calder

Mechanisms of action of fatty acids on inflammatory processes in macrophages
Professor Philip Calder

Effect of high dose, pharmaceutical grade omega-3 fatty acids on serum fibrosis markers, insulin sensitivity, macrovascular and microvascualr function and cardiovascular risk markers in patients with non alcoholic fatty liver disease
Professors Christopher Byrne , Philip Calder , Geraldine Clough & Nick Curzen and Drs Kathryn Nash, Nick Sheron, Mark Wright and Charles Peebles

Polyunsaturated fatty acid biosynthesis and macrophage function
Doctors Graham Burdge & Karen Lillycrop , Professors Philip Calder & Cliff Shearman

Influence of maternal fat intake on cardiovascular function in the offspring
Doctors Graham Burdge , Karen Lillycrop & Christopher Torrens and Professors Mark Hanson , Geraldine Clough & Philip Calder

Influence of salmon intake in pregnant women on markers and manifestations of allergic disease in their offspring
Professor Philip Calder

Fatty acids and functional responses of cord blood immune cells
Professor Philip Calder

Lung surfactant

Figure 1

Lung surfactant is the lipid:protein complex secreted by the alveolar type 2 epithelial cell of the lungs.  The phospholipid content of lung surfactant  generates low surface tension/high surface pressure at the air:liquid interface, prevents collapse of the gas exchange regions of the lung and is essential for breathing.  Absence or inactivation of surfactant  causes severe respiratory failure both in preterm infants and in  adults.

Decreased lung surfactant

Figure 2

Decreased lung surfactant in acute respiratory distress syndrome can be due to impaired  synthesis and secretion by the type 2 epithelial cells or to increased hydrolysis and oxidation in the air space.

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