Wim Martinet

By Dorien M. Schrijvers, Guido R.Y. De Meyer and Wim Martinet

Part of the book: Atherogenesis

By Ilse Van Brussel, Hidde Bult, Wim Martinet, Guido R.Y. De Meyer and Dorien M. Schrijvers

Part of the book: Current Trends in Atherogenesis

By Wilhelmus J. Kwanten, Wim Martinet and Sven M. Francque

Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients. The potential role of autophagy in disease is increasingly recognised and investigated. To date, a key role of autophagy in hepatic lipid metabolism is recognised and dysfunctional autophagy might be an underlying cause of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the exact role of autophagy in lipid metabolism remains controversial, with both a lipolytic function of autophagy and lipogenic function reported. This chapter aims to review the current knowledge on autophagy in NAFLD, with a special focus on its role in hepatic lipid metabolism, hepatic glucose metabolism and insulin resistance, steatohepatitis, hepatocellular injury and hepatic fibrogenesis. Finally, interaction with another cellular homeostatic process, the unfolded protein response (UPR), will be briefly discussed.

Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology

By Dorien G. De Munck, Guido R.Y. De Meyer and Wim Martinet

Food restriction is a promising therapy for many age-associated pathologies as it stimulates the health-supportive mechanism autophagy. Because atherosclerosis is an inflammatory, age-related disease, dietary modification can be an important strategy in preventing atherosclerotic plaque development. A cholesterol-supplemented diet, used to induce plaque formation in rabbits, induces a pronounced hypercholesterolemia, which can be reversed after 4 weeks of normal diet. However, food restriction induces a further increase in circulating LDL cholesterol. These elevated cholesterol levels are associated with the induction of autophagy. Although neither a short-term normal diet nor food restriction alters plaque size, rabbits fed a normal diet show signs of increased plaque stability such as elevated collagen content and decreased expression of vascular cell adhesion molecule (VCAM)-1. Surprisingly, these favorable effects are not present after 4 weeks of food restriction. On the contrary, atherosclerotic plaques of food-restricted rabbits displayed enhanced apoptosis, a process known to further undermine plaque stability. In conclusion, severe short-term food restriction in rabbits prevents stabilization of atherosclerotic plaques as observed after regular cholesterol withdrawal via a normal diet.

Part of the book: Atherosclerosis