NUTR 470 1st Edition Lecture 15 -Nutritional Regulation ofLipolysis-Lipolysis• Definition —Lipolysis is the breakdown of fat stored infat cells.-Location• Adipose tissue• During lipolysis, free fatty acids are releasedinto the bloodstream and circulatethroughout the body.-Hormone-sensitive lipase (HSL) • catalyzeshydrolysis of triglycerides, diglycerides, andmonoglyceride.-Monoglyceride lipase (MGL) • catalyzeshydrolysis of monoglyceride to form glyceroland free fatty acid.-Hormone-stimulated Lipolysis• Under basal conditions -Model of the mechanism of hormone-stimulated lipolysis-HSL is not associatedwith the lipid droplet,while perilipin decoratesthe lipid droplet andhindersaccess of thedroplet to HSL.-ALBP and other fattyacid binding proteins arefound abundantly in thecytosol. -HSL and perilipin arephosphorylated and HSLtranslocates to the lipiddroplet.-ALBP binds to HSL,preventing fatty acid inhibition of the enzyme’shydrolytic activity, andsequesters and transportsthe released fatty acids.-Regulation of Lipolysis• The rates of free fatty acid release fromadipose tissue are subjected to theregulation by hormones.-Hormones that favor lipolysis• Epinephrine and norepinephrine• Glucagon• Glucocorticoids-These hormones activate HSL.• Hormone that suppresses lipolysis-The rates of free fatty acid release fromadipose tissue are subjected to theregulation by hormones.-Insulin is the most powerful anti-lipolytichormone.-A principal action of insulin in adiposetissue is to inhibit the activity of hormone sensitive lipase (HSL).• Stimulation of HSL-Hormonal control of lipolysis is carriedout by altering the phosphorylation stateof HSL.-Glucagon, norepinephrine, or epinephrinebinds to the G protein-coupled receptor,which in turnactivates adenylate cyclase toproduce cyclic AMP.-cAMP consequently activates protein kinaseA, which phosphorylates and activates HSL.• Suppression of HSL-Insulin activates protein phosphatase 2A,which dephosphorylates HSL, therebyinhibiting its activity.-Insulin also activates the enzymephosphodiesterase, which breaks downcAMP and stopsthe re-phosphorylationeffects of protein kinase A.-When glucose levels are low• Lipolysis in fat cells responds to changesin the nutritional state.• Insulin levels are decreased whereasglucagon levels are elevated, which in turnbring about an increase in lipolysis throughstimulating HSL.-When glucose levels are high• Lipolysis in fat cells responds to changesin the nutritional state.• Insulin levels are elevated whereas glucagonlevels are decreased, which in turn bringabout a suppression of lipolysis throughinhibiting HSL.-Fate of Free Fatty Acids• Free fatty acids as fuels-Lipolysis releases free fatty acids intothe circulation.-Free fatty acids uptake by muscle and heartare used as a fuel.-Uptake of free fatty acids requires transportercomplex including fatty acid binding proteinand fatty acid transport protein.• Synthesis of triglycerides-Following uptake, free fatty acids are reesterifiedin liver cells and fat cells.-Glycerol-3-phosphate, the active formglycerol, is required for free fatty acids reesterification.• Fatty Acid Cycling-Uptake of free fatty acids by fat cells istermed as fatty acid cycling.-Fatty acid cycling is a important source offatty acids, which are then used for thesynthesis of triglycerides.-Glycerol cycling • Lipolysis also leads to the release ofglycerol into the circulation.• Uptake of glycerol by fat cells is termed asglycerol cycling.• Previously, it is believed that fat cells do nothave glycerol kinase.• Glycerol kinase is now found in fat cells. Yet,its role in the synthesis of triglycerides isquestionable.-Lipolysis and Insulin Resistance• Insulin resistance is defined as impairmentin actions of insulin.• Inefficiency in suppressing lipolysis• An elevation in lipolysis is commonly seen inobesity, although insulin levels are high.• Elevated levels of free fatty acids cause orexacerbate insulin resistance.-Summary-Hormone-sensitive lipase-Regulation of lipolysis-Basic concepts of