To obtain energy from fat, triglycerides must first be broken down by hydrolysis into their two principal components, fatty acids and glycerol.

This process, called lipolysis , takes place in the cytoplasm. The resulting fatty acids are oxidized by β-oxidation into acetyl CoA, which is used by the Krebs cycle. The glycerol that is released from triglycerides after lipolysis directly enters the glycolysis pathway as DHAP.

Because one triglyceride molecule yields three fatty acid molecules with as much as 16 or more carbons in each one, fat molecules yield more energy than carbohydrates and are an important source of energy for the human body.

Triglycerides yield more than twice the energy per unit mass when compared to carbohydrates and proteins. Therefore, when glucose levels are low, triglycerides can be converted into acetyl CoA molecules and used to generate ATP through aerobic respiration.

The breakdown of fatty acids, called fatty acid oxidation or beta β -oxidation , begins in the cytoplasm, where fatty acids are converted into fatty acyl CoA molecules.

This fatty acyl CoA combines with carnitine to create a fatty acyl carnitine molecule, which helps to transport the fatty acid across the mitochondrial membrane. Once inside the mitochondrial matrix, the fatty acyl carnitine molecule is converted back into fatty acyl CoA and then into acetyl CoA.

The newly formed acetyl CoA enters the Krebs cycle and is used to produce ATP in the same way as acetyl CoA derived from pyruvate. Figure 3. Click for a larger image. During fatty acid oxidation, triglycerides can be broken down into acetyl CoA molecules and used for energy when glucose levels are low.

If excessive acetyl CoA is created from the oxidation of fatty acids and the Krebs cycle is overloaded and cannot handle it, the acetyl CoA is diverted to create ketone bodies. These ketone bodies can serve as a fuel source if glucose levels are too low in the body. Ketones serve as fuel in times of prolonged starvation or when patients suffer from uncontrolled diabetes and cannot utilize most of the circulating glucose.

In both cases, fat stores are liberated to generate energy through the Krebs cycle and will generate ketone bodies when too much acetyl CoA accumulates. In this ketone synthesis reaction, excess acetyl CoA is converted into hydroxymethylglutaryl CoA HMG CoA. HMG CoA is a precursor of cholesterol and is an intermediate that is subsequently converted into β-hydroxybutyrate, the primary ketone body in the blood.

Figure 4. Excess acetyl CoA is diverted from the Krebs cycle to the ketogenesis pathway. This reaction occurs in the mitochondria of liver cells. The result is the production of β-hydroxybutyrate, the primary ketone body found in the blood.

Organs that have classically been thought to be dependent solely on glucose, such as the brain, can actually use ketones as an alternative energy source.

This keeps the brain functioning when glucose is limited. When ketones are produced faster than they can be used, they can be broken down into CO 2 and acetone. The acetone is removed by exhalation. This effect provides one way of telling if a diabetic is properly controlling the disease.

The carbon dioxide produced can acidify the blood, leading to diabetic ketoacidosis, a dangerous condition in diabetics.

Ketones oxidize to produce energy for the brain. beta β -hydroxybutyrate is oxidized to acetoacetate and NADH is released. An HS-CoA molecule is added to acetoacetate, forming acetoacetyl CoA. The carbon within the acetoacetyl CoA that is not bonded to the CoA then detaches, splitting the molecule in two.

This carbon then attaches to another free HS-CoA, resulting in two acetyl CoA molecules. These two acetyl CoA molecules are then processed through the Krebs cycle to generate energy. Figure 5. When glucose is limited, ketone bodies can be oxidized to produce acetyl CoA to be used in the Krebs cycle to generate energy.

When glucose levels are plentiful, the excess acetyl CoA generated by glycolysis can be converted into fatty acids, triglycerides, cholesterol, steroids, and bile salts. This process, called lipogenesis , creates lipids fat from the acetyl CoA and takes place in the cytoplasm of adipocytes fat cells and hepatocytes liver cells.

When you eat more glucose or carbohydrates than your body needs, your system uses acetyl CoA to turn the excess into fat. Although there are several metabolic sources of acetyl CoA, it is most commonly derived from glycolysis.

Acetyl CoA availability is significant, because it initiates lipogenesis. Lipogenesis begins with acetyl CoA and advances by the subsequent addition of two carbon atoms from another acetyl CoA; this process is repeated until fatty acids are the appropriate length.

Because this is a bond-creating anabolic process, ATP is consumed. However, the creation of triglycerides and lipids is an efficient way of storing the energy available in carbohydrates. Triglycerides and lipids, high-energy molecules, are stored in adipose tissue until they are needed.

Although lipogenesis occurs in the cytoplasm, the necessary acetyl CoA is created in the mitochondria and cannot be transported across the mitochondrial membrane.

To solve this problem, pyruvate is converted into both oxaloacetate and acetyl CoA. Two different enzymes are required for these conversions. Oxaloacetate forms via the action of pyruvate carboxylase, whereas the action of pyruvate dehydrogenase creates acetyl CoA. Oxaloacetate and acetyl CoA combine to form citrate, which can cross the mitochondrial membrane and enter the cytoplasm.

In the cytoplasm, citrate is converted back into oxaloacetate and acetyl CoA. Oxaloacetate is converted into malate and then into pyruvate. Pyruvate crosses back across the mitochondrial membrane to wait for the next cycle of lipogenesis.

The acetyl CoA is converted into malonyl CoA that is used to synthesize fatty acids. Figure 6 summarizes the pathways of lipid metabolism.

These include cortisol, glucagon, growth hormone GH , and adrenocorticotropic hormone ACTH. Dietary compounds, such as caffeine and calcium, also stimulate lipolysis.

Each of these substances binds and act on their respective membrane-bound receptors and elicit a signaling cascade using a common second messenger, cyclic AMP. Cyclic AMP then binds to and activates protein kinase A PKA.

Once PKA is enzymatically active, it phosphorylates HSL, the most important of the three enzymes involved in initiating lipolysis because it is enzymatically activated in all stages of hydrolysis. ATGL performs the first step of TAG hydrolysis, generating diacylglycerols and FAs.

Its activity is tightly regulated by two accessory proteins: CGI and G0S2. CGI coactivates the hydrolase activity of ATGL and G0S2 inactivates the hydrolase activity of ATGL.

HSL performs the second step and hydrolyzes DAGs, generating monoacylglycerols and FAs. MGL is selective for MGs and generates glycerol and the third FA. Short and medium-chain fatty acids diffuse freely into the cytosol and mitochondria of cells. Long-chain fatty acids must undergo protein-mediated transport across the cell membrane into the cytosol via fatty acid translocase FAT or fatty acid-binding protein FABP.

Acyl-CoA synthase then converts the fatty acids to fatty acyl-CoA. The fatty acyl-CoA must now be transported into the mitochondria through the outer mitochondrial membrane and is done so by carnitine palmitoyltransferase-I CPT-I where it becomes fatty acyl-carnitine. The fatty acyl-carnitine is then transported across the inner membrane into the mitochondrial matrix by carnitine acyl-translocase CAT and converted back to fatty acyl-CoA by palmitoyltransferase-II CPT-II where it is now ready for oxidation.

Beta oxidation is the degradation of fatty acids by removing two carbons at a time. It is the primary pathway for catabolism of fatty acids and takes place in the mitochondrial matrix of tissues such as the liver, muscle, and adipose.

Two-carbon fragments are successively removed from the carboxyl end of the fatty acyl-CoA, producing NADH, FADH, and Acetyl CoA, which is used in the TCA cycle to make ATP.

Fatty acids with odd numbers of carbon ultimately yield one mole of propionyl-CoA, which is converted to succinyl CoA so that it is usable in the TCA cycle. Beta oxidation is also important as the primary regulator of movement through the pyruvate dehydrogenase PDH complex. When rates of fatty acid oxidation are high, PDH activity decreases, which limits glycolysis, which is significant because patients with a deficiency in fatty acid oxidation have a compensatory increase in glucose oxidation and impaired gluconeogenesis.

Ketone levels are low during normal feeding and physiological status. They are used by the heart and skeletal muscles to preserve the limited glucose for use by the brain and erythrocytes.

During the fasting state, fatty acids are oxidized in the liver to acetyl CoA, which converts to the ketone bodies acetoacetate and beta-hydroxybutyrate. These high levels of ketones also inhibit PDH activity and fatty acid oxidation, to conserve glucose and permit entry into the brain where they can serve as sources for energy.

Normally during a fast, muscle metabolizes ketone bodies as rapidly as the liver releases them preventing their accumulation in the blood. If ketones increase sufficiently in the blood, this can result in ketoacidosis, which is especially prevalent in people with type I diabetes and require close monitoring.

There are currently several strategies in place to estimate lipolysis and these generally fall into two categories: non-activity-based methods and activity-based methods. The non-activity-based methods involve determining the quantity of the associated enzymes and regulatory proteins.

The activity-based methods involve measuring the activity of the associated enzymes directly. Over the last several years, new and updated information has come to light, and the opinions of lipolysis have changed.

It is now known that the measurement of mRNA or protein expression used in the non-activity-based methods is often not enough to estimate the capacity of lipolysis. A combination of methods is necessary. Neutral lipid storage disease with myopathy NLSDM — a rare inherited disorder arising from mutations in the ATGL gene, which results in systemic TAG accumulation, myopathy, cardiac abnormalities, and hepatomegaly.

Chanarin-Dorfman syndrome or NLSD with ichthyosis NLSD-I results from mutations in CGI, the activator of ATGL. They also exhibit systemic TAG accumulation, mild myopathy, and hepatomegaly but also present with ichthyosis, which is a skin disorder characterized by dry, thickened, scaly skin.

Familial partial lipodystrophy FPLD type 4 is associated with a mutation in the PLIN1 gene coding for perilipin 1. It is characterized phenotypically by loss of subcutaneous fat from the extremities. Histologically, the six patients with this mutation have small adipocytes with increased macrophage infiltration and abundant fibrosis.

Familial partial lipodystrophy FPLD type 6 occurs due to a mutation in the LIPE gene coding for hormone-sensitive lipase. It is characterized by abnormal subcutaneous fat distribution, and thus the complications commonly associated with it it.

These include dysregulated lipolysis, insulin resistance, diabetes mellitus, increased fat storage in bodily organs, and dyslipidemia; others may even develop muscular dystrophy as indicated by elevated serum creatine phosphokinase.

There are many disorders of fat metabolism that present with serious and specific characteristics but are not discussed here as they are beyond the scope of lipolysis, specifically.

These include, but are not limited to, fatty acid oxidation disorders FAODs such as MCAD deficiency or primary carnitine deficiency and peroxisomal disorders such as Zellweger syndrome and adrenoleukodystrophy.

Alterations in lipolysis are often associated with obesity. These changes include increased basal rates of lipolysis, which may promote the development of insulin resistance and also diminished responsiveness to stimulated lipolysis.

Furthermore, adipose tissue of insulin-resistant people displays a lack of proteins involved in mitochondrial function. Mitochondria-derived energy sources function in lipogenesis in adipose tissue.

Obesity is characterized primarily by an excess of WAT due to hypertrophy of adipocytes that results from increased TAG storage. Obesity is a rampant health problem across the world due to its association with several disorders, including insulin resistance, type II diabetes, hypertension, and atherosclerosis.

Disclosure: Michael Edwards declares no relevant financial relationships with ineligible companies. Disclosure: Shamim Mohiuddin declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Turn recording back on. National Library of Medicine Rockville Pike Bethesda, MD Web Policies FOIA HHS Vulnerability Disclosure. Help Accessibility Careers. Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation. Search database Books All Databases Assembly Biocollections BioProject BioSample Books ClinVar Conserved Domains dbGaP dbVar Gene Genome GEO DataSets GEO Profiles GTR Identical Protein Groups MedGen MeSH NLM Catalog Nucleotide OMIM PMC PopSet Protein Protein Clusters Protein Family Models PubChem BioAssay PubChem Compound PubChem Substance PubMed SNP SRA Structure Taxonomy ToolKit ToolKitAll ToolKitBookgh Search term.

StatPearls [Internet]. Treasure Island FL : StatPearls Publishing; Jan-. Show details Treasure Island FL : StatPearls Publishing ; Jan-. Search term. Biochemistry, Lipolysis Michael Edwards ; Shamim S. Author Information and Affiliations Authors Michael Edwards 1 ; Shamim S.

Affiliations 1 Loyola University Medical Center. Introduction Lipolysis is the metabolic process through which triacylglycerols TAGs break down via hydrolysis into their constituent molecules: glycerol and free fatty acids FFAs.

Fundamentals Triacylglycerol Synthesis TAGs, which provide the body with a significant source of energy, are obtained from the diet or are synthesized endogenously, mainly in the liver. Triacylglycerol Hydrolysis During times of energy deprivation, WAT is stimulated via homeostatic control to shift toward higher net rates of lipolysis.

Issues of Concern Defective lipolysis in non-adipose tissues impairs their normal function, leading to excessive TAG accumulation and lipid storage disease. Cellular Level As previously described, hormones bind to cell surface receptors i.

Molecular Level Lipids have diverse structures but are all similar in that they are insoluble in water. Function Fatty acids are carried on the albumin in the blood. Triacylglycerol Hydrolysis As stated previously, during times of energy deprivation, WAT is stimulated by hormonal and biochemical signals to increase lipolysis.

Fatty Acid Metabolism Short and medium-chain fatty acids diffuse freely into the cytosol and mitochondria of cells. Beta oxidation Beta oxidation is the degradation of fatty acids by removing two carbons at a time.

Ketone synthesis Ketone levels are low during normal feeding and physiological status. Testing There are currently several strategies in place to estimate lipolysis and these generally fall into two categories: non-activity-based methods and activity-based methods.

Pathophysiology Neutral lipid storage disease with myopathy NLSDM — a rare inherited disorder arising from mutations in the ATGL gene, which results in systemic TAG accumulation, myopathy, cardiac abnormalities, and hepatomegaly.

Clinical Significance Alterations in lipolysis are often associated with obesity. Review Questions Access free multiple choice questions on this topic. Comment on this article. References 1. Bolsoni-Lopes A, Alonso-Vale MI. Lipolysis and lipases in white adipose tissue - An update.

Arch Endocrinol Metab. Schweiger M, Eichmann TO, Taschler U, Zimmermann R, Zechner R, Lass A. Measurement of lipolysis. Methods Enzymol. Engin AB.

What Is Lipotoxicity? Adv Exp Med Biol. Tansey JT, Sztalryd C, Hlavin EM, Kimmel AR, Londos C. The central role of perilipin a in lipid metabolism and adipocyte lipolysis. IUBMB Life. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, Madeo F.

FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling. Cell Metab. Ahmadian M, Wang Y, Sul HS. Lipolysis in adipocytes. Int J Biochem Cell Biol. Gandotra S, Le Dour C, Bottomley W, Cervera P, Giral P, Reznik Y, Charpentier G, Auclair M, Delépine M, Barroso I, Semple RK, Lathrop M, Lascols O, Capeau J, O'Rahilly S, Magré J, Savage DB, Vigouroux C.

Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med. Albert JS, Yerges-Armstrong LM, Horenstein RB, Pollin TI, Sreenivasan UT, Chai S, Blaner WS, Snitker S, O'Connell JR, Gong DW, Breyer RJ, Ryan AS, McLenithan JC, Shuldiner AR, Sztalryd C, Damcott CM.

Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr. Bódis K, Roden M.

Series ISSN : Series E-ISSN : Edition Number : 1. Number of Pages : XIV, Topics : Biochemistry, general. Policies and ethics. Skip to main content. Editors: Shimon Gatt 0 , Louis Freysz 1 , Paul Mandel 2.

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Page 1 Navigate to page number of 4. Front Matter Pages i-xiv. Enzymes Metabolizing Phospholipids: From Infancy to Middle Age Enzymes Metabolizing Phospholipids: From Infancy to Middle Age R. Dawson Pages Enzymes of the Metabolism of Fatty Acids and Neutral Glycerides Front Matter Pages Fatty Acid Biosynthesis during Brain Development J.

Bourre, S. Pollet, M. Paturneau-Jouas, N. Baumann Pages The Role of Soluble Acyl-Thioester Hydrolase in Fatty Acid Chain-Length Termination in Rabbit Mammary Gland and Liver Jens Knudsen, Linda Chivers, Raymond Dils Pages Stereochemical Studies of Hydrogen Incorporation from Nucleotides with Fatty Acid Synthetase from Brevibacterium ammoniagenes Y.

Seyama, T. Kasama, T. Yamakawa, A. Kawaguchi, S. Okuda Pages Cholesterol Oxidase as a Probe for Studying Membrane Composition and Organization Y. Barenholz, E. Patzer, N. Moore, R. Wagner Pages Adsorption and Activation of Pancreatic Lipase at Interfaces C.

Chapus, M. Semeriva, M. Charles, P. Desnuelle Pages Mode of Action of Pancreatic Colipase Bengt Borgström Pages Studies of Lipase and Phospholipase A2 Acting on Lipid Monolayers R. Verger, J.

Rietsch, F. Pattus, F. Ferrato, G. Pieroni, G. De Haas et al. Pages Inhibition of Lipase Adsorption at Interfaces. Role of Bile Salts Micelles and Colipase D. Lairon, G. It is the primary pathway for catabolism of fatty acids and takes place in the mitochondrial matrix of tissues such as the liver, muscle, and adipose.

Two-carbon fragments are successively removed from the carboxyl end of the fatty acyl-CoA, producing NADH, FADH, and Acetyl CoA, which is used in the TCA cycle to make ATP. Fatty acids with odd numbers of carbon ultimately yield one mole of propionyl-CoA, which is converted to succinyl CoA so that it is usable in the TCA cycle.

Beta oxidation is also important as the primary regulator of movement through the pyruvate dehydrogenase PDH complex. When rates of fatty acid oxidation are high, PDH activity decreases, which limits glycolysis, which is significant because patients with a deficiency in fatty acid oxidation have a compensatory increase in glucose oxidation and impaired gluconeogenesis.

Ketone levels are low during normal feeding and physiological status. They are used by the heart and skeletal muscles to preserve the limited glucose for use by the brain and erythrocytes. During the fasting state, fatty acids are oxidized in the liver to acetyl CoA, which converts to the ketone bodies acetoacetate and beta-hydroxybutyrate.

These high levels of ketones also inhibit PDH activity and fatty acid oxidation, to conserve glucose and permit entry into the brain where they can serve as sources for energy.

Normally during a fast, muscle metabolizes ketone bodies as rapidly as the liver releases them preventing their accumulation in the blood.

If ketones increase sufficiently in the blood, this can result in ketoacidosis, which is especially prevalent in people with type I diabetes and require close monitoring. There are currently several strategies in place to estimate lipolysis and these generally fall into two categories: non-activity-based methods and activity-based methods.

The non-activity-based methods involve determining the quantity of the associated enzymes and regulatory proteins. The activity-based methods involve measuring the activity of the associated enzymes directly.

Over the last several years, new and updated information has come to light, and the opinions of lipolysis have changed. It is now known that the measurement of mRNA or protein expression used in the non-activity-based methods is often not enough to estimate the capacity of lipolysis.

A combination of methods is necessary. Neutral lipid storage disease with myopathy NLSDM — a rare inherited disorder arising from mutations in the ATGL gene, which results in systemic TAG accumulation, myopathy, cardiac abnormalities, and hepatomegaly.

Chanarin-Dorfman syndrome or NLSD with ichthyosis NLSD-I results from mutations in CGI, the activator of ATGL. They also exhibit systemic TAG accumulation, mild myopathy, and hepatomegaly but also present with ichthyosis, which is a skin disorder characterized by dry, thickened, scaly skin.

Familial partial lipodystrophy FPLD type 4 is associated with a mutation in the PLIN1 gene coding for perilipin 1. It is characterized phenotypically by loss of subcutaneous fat from the extremities.

Histologically, the six patients with this mutation have small adipocytes with increased macrophage infiltration and abundant fibrosis. Familial partial lipodystrophy FPLD type 6 occurs due to a mutation in the LIPE gene coding for hormone-sensitive lipase.

It is characterized by abnormal subcutaneous fat distribution, and thus the complications commonly associated with it it. These include dysregulated lipolysis, insulin resistance, diabetes mellitus, increased fat storage in bodily organs, and dyslipidemia; others may even develop muscular dystrophy as indicated by elevated serum creatine phosphokinase.

There are many disorders of fat metabolism that present with serious and specific characteristics but are not discussed here as they are beyond the scope of lipolysis, specifically.

These include, but are not limited to, fatty acid oxidation disorders FAODs such as MCAD deficiency or primary carnitine deficiency and peroxisomal disorders such as Zellweger syndrome and adrenoleukodystrophy. Alterations in lipolysis are often associated with obesity.

These changes include increased basal rates of lipolysis, which may promote the development of insulin resistance and also diminished responsiveness to stimulated lipolysis. Furthermore, adipose tissue of insulin-resistant people displays a lack of proteins involved in mitochondrial function.

Mitochondria-derived energy sources function in lipogenesis in adipose tissue. Obesity is characterized primarily by an excess of WAT due to hypertrophy of adipocytes that results from increased TAG storage.

Obesity is a rampant health problem across the world due to its association with several disorders, including insulin resistance, type II diabetes, hypertension, and atherosclerosis.

Disclosure: Michael Edwards declares no relevant financial relationships with ineligible companies. Disclosure: Shamim Mohiuddin declares no relevant financial relationships with ineligible companies. This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.

You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Turn recording back on. National Library of Medicine Rockville Pike Bethesda, MD Web Policies FOIA HHS Vulnerability Disclosure. Help Accessibility Careers. Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation. Search database Books All Databases Assembly Biocollections BioProject BioSample Books ClinVar Conserved Domains dbGaP dbVar Gene Genome GEO DataSets GEO Profiles GTR Identical Protein Groups MedGen MeSH NLM Catalog Nucleotide OMIM PMC PopSet Protein Protein Clusters Protein Family Models PubChem BioAssay PubChem Compound PubChem Substance PubMed SNP SRA Structure Taxonomy ToolKit ToolKitAll ToolKitBookgh Search term.

StatPearls [Internet]. Treasure Island FL : StatPearls Publishing; Jan-. Show details Treasure Island FL : StatPearls Publishing ; Jan-. Search term. Biochemistry, Lipolysis Michael Edwards ; Shamim S.

Author Information and Affiliations Authors Michael Edwards 1 ; Shamim S. Affiliations 1 Loyola University Medical Center. Introduction Lipolysis is the metabolic process through which triacylglycerols TAGs break down via hydrolysis into their constituent molecules: glycerol and free fatty acids FFAs.

Fundamentals Triacylglycerol Synthesis TAGs, which provide the body with a significant source of energy, are obtained from the diet or are synthesized endogenously, mainly in the liver.

Triacylglycerol Hydrolysis During times of energy deprivation, WAT is stimulated via homeostatic control to shift toward higher net rates of lipolysis. Issues of Concern Defective lipolysis in non-adipose tissues impairs their normal function, leading to excessive TAG accumulation and lipid storage disease.

Cellular Level As previously described, hormones bind to cell surface receptors i. Molecular Level Lipids have diverse structures but are all similar in that they are insoluble in water. Function Fatty acids are carried on the albumin in the blood. Triacylglycerol Hydrolysis As stated previously, during times of energy deprivation, WAT is stimulated by hormonal and biochemical signals to increase lipolysis.

Fatty Acid Metabolism Short and medium-chain fatty acids diffuse freely into the cytosol and mitochondria of cells. Beta oxidation Beta oxidation is the degradation of fatty acids by removing two carbons at a time. Ketone synthesis Ketone levels are low during normal feeding and physiological status.

Testing There are currently several strategies in place to estimate lipolysis and these generally fall into two categories: non-activity-based methods and activity-based methods.

Pathophysiology Neutral lipid storage disease with myopathy NLSDM — a rare inherited disorder arising from mutations in the ATGL gene, which results in systemic TAG accumulation, myopathy, cardiac abnormalities, and hepatomegaly. Clinical Significance Alterations in lipolysis are often associated with obesity.

Review Questions Access free multiple choice questions on this topic. Comment on this article. References 1. Bolsoni-Lopes A, Alonso-Vale MI. Lipolysis and lipases in white adipose tissue - An update.

Arch Endocrinol Metab. Schweiger M, Eichmann TO, Taschler U, Zimmermann R, Zechner R, Lass A. Measurement of lipolysis. Methods Enzymol. Engin AB.

What Is Lipotoxicity? Adv Exp Med Biol. Tansey JT, Sztalryd C, Hlavin EM, Kimmel AR, Londos C. The central role of perilipin a in lipid metabolism and adipocyte lipolysis.

IUBMB Life. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, Madeo F. FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling. Cell Metab. Ahmadian M, Wang Y, Sul HS.

Lipolysis in adipocytes. Int J Biochem Cell Biol. Gandotra S, Le Dour C, Bottomley W, Cervera P, Giral P, Reznik Y, Charpentier G, Auclair M, Delépine M, Barroso I, Semple RK, Lathrop M, Lascols O, Capeau J, O'Rahilly S, Magré J, Savage DB, Vigouroux C. Perilipin deficiency and autosomal dominant partial lipodystrophy.

N Engl J Med. Albert JS, Yerges-Armstrong LM, Horenstein RB, Pollin TI, Sreenivasan UT, Chai S, Blaner WS, Snitker S, O'Connell JR, Gong DW, Breyer RJ, Ryan AS, McLenithan JC, Shuldiner AR, Sztalryd C, Damcott CM.

Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr. Bódis K, Roden M. Energy metabolism of white adipose tissue and insulin resistance in humans.

Eur J Clin Invest. Copyright © , StatPearls Publishing LLC. Bookshelf ID: NBK PMID: PubReader Print View Cite this Page Edwards M, Mohiuddin SS. Biochemistry, Lipolysis. In: StatPearls [Internet]. In this Page. Introduction Fundamentals Issues of Concern Cellular Level Molecular Level Function Mechanism Testing Pathophysiology Clinical Significance Review Questions References.

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Hill, J. Dietary fat intake and regulation of energy balance: implications for obesity. Carriere, F. et al. Gastric and pancreatic lipase levels during a test meal in dogs. Nordskog, B. An examination of the factors affecting intestinal lymphatic transport of dietary lipids.

Drug Deliv. Phan, C. Intestinal lipid absorption and transport. Kawai, T. Importance of lipolysis in oral cavity for orosensory detection of fat. Article CAS Google Scholar. Miled, N. Digestive lipases: from three-dimensional structure to physiology. Biochimie 82 , — Ghishan, F. Isolated congenital lipase-colipase deficiency.

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Gastroenterology , — Borgstrom, B. Binding of pancreatic colipase to interfaces: effects of detergents. FEBS Lett. Bowyer, R. Effect of a satiating meal on the concentrations of procolipase propeptide in the serum and urine of normal and morbidly obese subjects.

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Lucas, C. Padwal, R. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

Hanefeld, M. The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial. Diabetes Obes. Carey, M. Lipid digestion and absorption.

Huggins, K. Protection against diet-induced obesity and obesity-related insulin resistance in group 1B PLA2-deficient mice. This study describes the role of pancreatic sPLA2 in dietary fat absorption. Richmond, B. Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A 2 -deficient mice.

Chang, T. Porcine pancreatic phospholipase A2 stimulates secretin release from secretin-producing cells. Ma, T. Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels. Cell Physiol. Molecular structure and tissue-specific expression of the mouse pancreatic phospholipase A 2 gene.

Gene , 65—72 Murakami, M. Phospholipase A2. Yuan, C. Pancreatic phospholipase A 2 : new views on old issues. Acta 23 , — Article Google Scholar. Mihelich, E. Structure-based design of a new class of anti-inflammatory drugs: secretory phospholipase A 2 inhibitors, SPI. Niessen, H. Type II secretory phospholipase A2 in cardiovascular disease: a mediator in atherosclerosis and ischemic damage to cardiomyocytes?

Structural analysis of phospholipase A2 from functional perspective. Characterization of a molten globule-like state induced by site-specific mutagenesis.

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This research shows that passive diffusion is an efficient process for fatty acids entering the adipocytes. Vassileva, G. The intestinal fatty acid binding protein is not essential for dietary fat absorption in mice. FASEB J. Abumrad, N. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation.

Homology with human CD Chen, M. Poirier, H. Localization and regulation of the putative membrane fatty-acid transporter FAT in the small intestine. Comparison with fatty acid-binding proteins FABP.

Greenwalt, D. Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet. Goudriaan, J. Intestinal lipid absorption is not affected in CD36 deficient mice. Schaffer, J. Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein.

Cell 79 , — Gimeno, R. Targeted deletion of fatty acid transport protein-4 results in early embryonic lethality. Herrmann, T. Mouse fatty acid transport protein 4 FATP4 : characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase.

Gene , 31—40 Coleman, R. Enzymes of triacylglycerol synthesis and their regulation. Lipid Res. This paper provides a comprehensive review of the latest developments in lipid metabolic enzymes. Polheim, D. Regulation of triglyceride biosynthesis in adipose and intestinal tissue.

Yen, C. Identification of a gene encoding MGAT1, a monoacylglycerol acyltransferase. Natl Acad. USA 99 , — Cao, J. Cloning and functional characterization of a mouse intestinal Acyl-CoA:monoacylglycerol acyltransferase, MGAT2.

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Kim, J. After binding to lipids, proteins take part in transporting lipids in plasma, so they are called apolipoproteins. Figure 2. Lipid metabolism in liver. The mainly lipid source of the liver is food. The lipids in food are mainly TG, and there are a small amount of PL and Ch.

In the small intestine, bile acids and pancreatic enzymes including pancreatic lipase, phospholipase A2, cholesterol esterase, etc. in bile hydrolyze lipids into free fatty acids FFA , glycerol and Fc. Then these molecules are absorbed by mucosal epithelial cells of the small intestine mainly jejunum , and are further esterified into TG, CE, etc.

in intestinal epithelial cells. Finally, TG, Ch and PL with apolipoprotein compose of lipoprotein chylomicron CM which will be absorbed by the lymphatic system and hydrolyzed by lipoproteinase of vascular endothelial cells to enter the liver.

FFA can be converted into energy by oxidation in hepatocytes for the consumption, or re-synthesize TG, PL and CE with 3-phosphoglycerate. The mainly source of endogenous fatty acids is the fat stored in the body's adipose tissue.

The fat in the fat cells is hydrolyzed into glycerol and fatty acids by the action of lipase. After being released into the blood, glycerol is dissolved in plasma while fatty acids are combined with plasma albumin for transport.

It can be used as a source of energy or ingested by liver cells again. In addition, hepatocytes also can produce fatty acids from the oxidation process of glucose and amino acids and synthesize TG by acetyl-CoA in hepatocytes.

In addition to ingesting the exogenous cholesterol from food, liver cells also synthesize endogenous cholesterol. Hepatocyte endoplasmic reticulum cholesterol biosynthesis involves more than 30 enzymes, such as acetoacetyl CoA.

Endogenously synthesized cholesterol and exogenous free cholesterol taken up by lipoprotein receptors must be transported through the liver.

The transport destinations are: 1 decomposition into primary bile acid and bile salts in the liver, then discharging into the capillary bile duct and bile through the transport pump on the capillary bile duct; 2 free cholesterol and phospholipids are directly excreted to the bile by multi-drug resistance transporter MDR ; 3 cholesterol ester and free cholesterol are converted to each other to form dynamic equilibrium.

Free cholesterol can be esterified into cholesterol ester by cholesterol acyltransferase ACAT and transported to the peripheral circulation in the form of VLDL. Cholesterol esters can be rapidly hydrolyzed to free cholesterol by cholesteryl ester hydrolase CEH as a precursor for the synthesis of bile acids; 4 VLDL consisting of apolipoproteins, phospholipids, etc.

reverses into human blood circulation, reaching hepatic stellate cells and steroid hormone secreting cells.

Figure 3. Lipid metabolism in pancreas. Pancreatic lipase is mainly secreted by pancreatic acinar cells and functions to digest the fat in the duodenum, including the classic pancreatic triglyceride lipase PTL , pancreatic lipase-related protein 1 PLRP1 and 2 PLRP2 , bile salt-stimulated lipase BSSL and pancreatic phospholipase A2 PLA2 , etc.

The source of pancreatic lipase is quite extensive. As the research progresses, it has been reported that PLRP2 is also expressed in lymphocytes and colonic epithelial cells, which are involved in the inflammatory response and regulating the intestinal flora, respectively.

The mammary gland of some mammals including humans, can secrete BSSL during lactation, which can be supplied to infants through milk to participate in their early fat digestion and absorption. It has also been found that BSSL is expressed in other tissues including liver, inflammatory cells, endothelial cells and platelets, suggesting that BSSL may be involved in the process of inflammation, arteriosclerosis, etc.

These important pancreatic lipases participant in the digestion of lipids such as triglycerides, cholesterol, and phospholipids , so that dietary fat can be fully utilized.