Obesity and post-prandial lipid metabolism. Feast or famine? Ian J. Martins a, *, Trevor G. Redgrave b a Centre for Human Genetics, Edith Cowan University, Joondalup Drive, Joondalup, Perth 6027, Australia b Physiology, School of Biomedical and Chemical Sciences, The University of Western Australia, Stirling Highway, Crawley, Perth 6009, Australia Received 17 September 2003; received in revised form 15 October 2003; accepted 21 October 2003 Abstract Both in Western countries and in third world countries there is an increasing incidence of obesity. Obesity per se or insulin resistance associated with obesity may increase cardiovascular risk factors including dyslipidemia, hypertension and Type 2 diabetes. Over the past decade the understanding has increased of specific mediators in the hypothalamus that are involved in regulating food intake and body weight. In obese humans fasting plasma lipids can be normal but postprandial lipid metabolism is abnormal with an accumulation of triglyceride-rich remnant lipoproteins. In viscerally obese men chylomicron remnant catabolism was markedly decreased when compared with lean individuals. The decreased clearance of chylomicron remnants in viscerally obese subjects may be explained by competition between chylomicron remnants and the increased hepatic production of VLDL for clearance by low density lipoprotein receptors. Increased food intake in rodent models of obesity was shown to be associated with a delay in the catabolism of remnant lipoprotein particles. Prevention of hyperphagia was found to correct the impairment in the metabolism of remnant lipoproteins. Under fasting and food restricted conditions the improvement of remnant metabolism was associated with an increased oxidation of remnant lipids as determined by a novel stable isotope breath test. Anti-obesity and lipid lowering drugs have been used for the treatment of obesity. Inhibitors of cholesterol synthesis inhibitors (statins) have been shown to be effective in treating dyslipidemia. Inhibition of cholesterol synthesis with Atorvastatin was shown to improve chylomicron metabolism by increasing chylomicron remnant catabolism in obese subjects as assessed by the newly developed stable isotope breath test. © 2004 Elsevier Inc. All rights reserved. Keywords: Chylomicron remnant; Obesity; Post-prandial; Stable isotope; Breath test; Hyperphagia; Food restriction; Dyslipidemia 1. Introduction In epidemiological studies, human obesity is clearly as- sociated with the increased risk for atherosclerosis, contrib- uting to the early onset of coronary artery disease. Obesity also has a well-documented association with Type 2 diabe- tes. Visceral obesity in particular increases the risk of ath- erosclerosis owing to both insulin resistance and dysli- poproteinemia. The metabolic basis for this association has not been established. Risk factors for atherosclerosis that could be exacera- bated by obesity include hypertension and hyperlipidemia, particularly hypertriglyceridemia. The contribution of post- prandial lipids to hypertriglyceridemia is attracting increas- ing attention. It is possible that the high risk of atherosclerosis is mainly due to the presence in plasma of these post-prandial lipoproteins since most individuals are in the post-prandial state for most of the day. Consistent with this view is that post-prandial hyperlipidemia is exacerbated in obesity. Post-prandial hyperlipidemia is mostly due to increased amounts of chylomicrons (CM) and chylomicron remnants (CR), their partially lipolyzed catabolic products. Currently there are limitations in the existing methods for assessing CR metabolism, which has hindered the understanding of the contribution of cholesterol-rich remnants to the devel- opment of coronary artery disease. The capacity to metab- olize CR contributes to the risk of atherosclerosis in man, as measured by the progression of coronary atherosclerosis determined angiographically [1,2]. The role of a new stable isotope breath test for CR metab- olism has been evaluated in rodent models of obesity and in viscerally obese humans. The associated hyperphagia with obese mice in common with postprandial hyperlipidemia has been assessed. The effects of food restriction on postprandial hyperlipidemia in obese mice as well as other interventions in man, lipid lowering drugs and exercise will be discussed. * Corresponding author. Tel.: +61-8-9400-5714; fax: +61-8-9400- 5851. E-mail address: imartins@cyllene.uwa.edu.au (I.J. Martins). Journal of Nutritional Biochemistry 15 (2004) 130 –141 0955-2863/04/$ – see front matter © 2004 Elsevier Inc. All rights reserved. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2003.10.006