Lipoprotein Metabolism in the Horse

Watson, Timothy David George (1991) Lipoprotein Metabolism in the Horse. PhD thesis, University of Glasgow.

Abstract

Hyperlipaemia is a disease of ponies in which massive hypertriglyceridaemia is associated with fatty infiltration of body tissues and organ failure. The aim of the work described here was to identify the causal defect in lipoprotein metabolism. Plasma lipid transport in healthy horses and ponies was first characterised. The high density lipoproteins (HDL) predominated and were homogeneous with respect to particle size and density. Three subfractions were found within the low density lipoproteins (LDL), and although the very low density lipoproteins (VLDL) were heterogeneous in size, discrete subpopulations were not identified. Two apolipoprotein (apo) B-100 like proteins were present in VLDL and LDL, and VLDL contained a third shorter species that appeared of hepatic origin. Lipoprotein lipase (LPL) and hepatic lipase (HL) were isolated and used to develop a selective assay for their measurement in post-heparin plasma. The activity of lecithin:cholesterol acyl transferase was dependent upon apoA-I and determined the mass of cholesteryl esters in HDL. Equine plasma lacked cholesteryl ester transfer activity because of a deficiency of the protein rather the masking of its function by an inhibitory factor. The plasma concentrations of triglyceride and VLDL were higher in Shetland ponies than in Thoroughbred horses. Moderate hypertriglyceridaemia was prevalent in Shetland pony mares during the last trimester of pregnancy and was associated with changes in VLDL composition similar to those found in ponies with hyperlipaemia. Although adult ponies showed no evidence of post-prandial lipaemia in response to feeding or an oral fat tolerance test, chylomicrons were found in the plasma of suckling foals where triglyceride and VLDL concentrations, and the activities of LPL and LCAT were higher than in adults. The plasma concentrations of LDL were also higher in the foals, and these lipoproteins were enriched with free cholesterol and phospholipid, and contained albumin and apoA-I. In the mares, lactation was associated with increased LPL activity. The plasma concentrations of triglyceride and VLDL were increased by an average of 165 and 20 fold, respectively, in ponies with hyperlipaemia. This was due to the emergence of larger, more buoyant particles that were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters and protein, specifically of apoB-100. The plasma concentrations of free fatty acids (FFA) and the activities of LPL and HL were increased. These data suggested that hepatic overproduction of VLDL, rather than compromised catabolism, was responsible for the condition. This was confirmed by kinetic analysis of plasma FFA and VLDL-triglyceride (VLDL-TG) metabolism in two ponies with hyperlipaemia, where the hepatic synthesis of VLDL-TG was 30 times higher than that in four healthy control ponies. This was driven by an increased flux of FFA from plasma into the liver. The residence time and fractional catabolic rate of VLDL was unaltered. Recycling of FFA into the plasma precursor pool from VLDL-TG lipolysis became a significant component of the hepatic input. This thesis concludes that lipid lowering agents that reduce VLDL synthesis by reducing FFA flux to the liver should prove effective in treating equine hyperlipaemia and that such agents might be prescribed to those ponies identified at risk from hyperlipaemia, for example those mares in the last trimester of pregnancy.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Veterinary science, Animal sciences, Physiology
• Date of Award: 1991
• Depositing User: Enlighten Team
• Unique ID: glathesis:1991-78323
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:33
• Last Modified: 30 Jan 2020 15:33
• URI: https://theses.gla.ac.uk/id/eprint/78323