Characterisation of chylomicron size distribution in subjects with metabolic syndrome: The effect of dietary fatty acid composition.

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Metabolic syndrome (MetS) is a cluster of metabolic abnormalities characterised by dysglycemia, raised blood pressure, elevated triglyceride concentration, low high density lipoprotein (HDL) cholesterol level and obesity (central adiposity) (Alberti et al., 2009). In Australia, up to approximately one third of the population is diagnosed with metabolic syndrome (Cameron, Magliano, Zimmet, Welborn, & Shaw, 2007). These numbers are only expected to increase in the coming years. The most unifying concept of metabolic syndrome is insulin resistance (Bremer, Mietus-Snyder, & Lustig, 2012). There is ample evidence suggesting altered lipoprotein homeostasis in insulin resistant state (Avramoglu, Basciano, & Adeli, 2006). Chylomicrons are lipoprotein particles that transport dietary fat from the intestine to tissues expressing lipoprotein lipase (LPL) such as skeletal muscle and adipose tissue. In insulin resistance, chylomicron homeostasis is impaired: either due to overproduction and/or delayed removal of chylomicron particles from circulation. The balance between chylomicron production and remnant clearance will determine the exposure of arterial tissues to pro-atherogenic remnants. In the fasting state, the circulating concentration of chylomicron particles is elevated in insulin resistance compared to normal controls (Curtin et al., 1996). Following a lipid-rich meal these defects are further manifested with elevated concentrations of chylomicrons persisting in circulation for a longer time compared to insulin sensitive controls (Avramoglu et al., 2006). As humans spend most of their lives in a postprandial state due to ingestion of several meals eaten in sequence, these insulin resistant subjects would be placed at greater risk of developing atherosclerosis, particularly if remnant (small, lipid-poor) chylomicron particles accumulate. Very little is known about the distribution profile of the chylomicron remnant fractions in the postprandial state, though it has been shown that these smaller particles have greater atherogenicity (Nakajima et al., 2010; Nakajima et al., 2011; Nakajima et al., 2012; Pang, Chan, Barrett, & Watts, 2012). The overarching aims of this project is to determine whether subjects with metabolic syndrome exhibit a more atherogenic size distribution of chylomicron particles than control subjects in the fasting and postprandial states. Furthermore, since dietary modification is an important supportive therapy for diabetes, metabolic syndrome and CVD, one aspect that may be important is the fatty acid composition of a meal. There is some evidence that dietary fatty acid composition may affect chylomicron homeostasis and fat oxidation rate (DeLany, Windhauser, Champagne, & Bray, 2000; Perez-Martinez et al., 2011; Silva et al., 2003). Thus this study will also investigate the effect of meals containing a range of vegetable oils each with differing fatty acids on the postprandial size distribution of chylomicron particles. Of particular interest is the effect of an edible oil, rice bran oil, that has been shown to have beneficial effects on cholesterol and hepatic lipoprotein concentration (Lai, Chen, Chen, Chang, & Cheng, 2012; Most, Tulley, Morales, & Lefevre, 2005).

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