chapter  9
38 Pages

Triacylglycerols and Cholesterol Metabolism

ByMichel Beylot, Fabien Forcheron, Dominique Letexier

CONTENTS General Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 Intake of Exogenous TAG and Cholesterol: Digestion

and Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 TAG Metabolism in Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

Sources of Fatty Acids Used for TAG Synthesis . . . . . . . . . . . . . . . . . . . . . . . 168 Circulating NEFA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 De Novo Lipogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 Uptake of Circulating Lipoproteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

Synthesis, Storage, and Secretion of TAGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172 TAG Metabolism in White Adipose Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

TAG Synthesis and Storage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 Sources of Fatty Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 Sources of Glycerol-3-phosphate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 TAG Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176

TAG Lipolysis and Release of Fatty Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 Hormone-Sensitive Lipase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 Other Lipases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 Perilipin and HSL Tranlocation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

TAG Metabolism in Other Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 Cholesterol Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182

Synthesis and Uptake of Cholesterol by Cells . . . . . . . . . . . . . . . . . . . . . . . . . 182 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

Triacylglycerols (TAGs) and cholesterol are quantitatively themost important circulating lipids. Both have important physiological roles and abnormalities in their metabolism are implicated in major pathologies such as obesity, insulin resistance, type 2 diabetes, dyslipidemia, and atherosclerosis. This chapter will present an overview of TAG metabolism and of its regulation

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of

with emphasis on intra-cellular metabolism and on recent findings. For cholesterol, the chapter focuses mainly on the mechanisms of cholesterol entry into and exit out of the cells and of the organism.