Cellular Lipid in Health and Disease
- 1st Edition - August 3, 2023
- Imprint: Academic Press
- Editor: James Mukasa Ntambi
- Language: English
- Hardback ISBN:9 7 8 - 0 - 4 4 3 - 2 1 8 2 2 - 4
- eBook ISBN:9 7 8 - 0 - 3 2 3 - 9 5 5 8 3 - 6
Cellular Lipid in Health and Disease presents a comprehensive and systematic coverage of the various roles lipids play in human biology. This book is organized in four par… Read more
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Request a sales quoteCellular Lipid in Health and Disease presents a comprehensive and systematic coverage of the various roles lipids play in human biology.
This book is organized in four parts covering the foundational concepts of lipid biology all the way to the therapeutic opportunities they present. The first part is dedicated to the basic concepts of cellular lipid, the roles it plays in the cell, structure and physiology, regulation mechanisms, storage, and utilization. The second part is focused on lipid metabolism, covering the organelles involved in lipid trafficking, metabolism in aging, cholesterol homeostasis, lipid droplets (LDs), and lipid oxidation. Part three is dedicated to the roles lipids play in specific disease states including renal, metabolic, cardiovascular, and fatty liver diseases. Other conditions include cancer, neurodegenerative diseases, and the intricate relationship between cellular lipids and autophagy. The final part covers therapeutic opportunities, including drug carrier systems, modeling lipid metabolism, and prevention therapeutics.
Cellular Lipid in Health and Disease is a complete reference targeted at graduate students and early career researchers in cell biology, biochemistry, and pharmacology. Research physicians can also benefit from the foundational content and links to pathologies and therapeutic opportunities.
- Offers a complete and systematic coverage of lipid biology
- Provides foundational content and establishes the needed connections to translational aspects of the research in this area
- Includes chapters on the therapeutic opportunities presented by lipids
Graduate students, researchers in the adjacent fields of Biochemistry, Pharmacology, Physiology and Cell Biology, Research Physicians in areas where Lipids plays a key role in disease states
CHAPTER 1 Structure and function of mammalian sphingolipids in health and disease
Mariona Rabionet, Robert Engel and Roger Sandhoff
1. Sphingolipids
2. The biological space of sphingolipid structures
2.1 Sphingoid bases
2.2 N-acylation of sphingoid bases
2.3 Headgroup modifications of sphingoid bases and ceramides
2.4 Noncanonical sphingolipids
3. Metabolism of sphingolipids in mammalian cells
3.1 Topology of sphingolipid metabolism
3.2 De novo sphingolipid biosynthesis pathway
3.3 Salvage and sphingomyelinase pathways
3.4 Hydrophilic headgroup modifications of ceramides
4. Physiological functions of sphingolipids
4.1 3-Ketodihydrosphingosines
4.2 Sphinganines
4.3 Dihydroceramides
4.4 Ceramides
4.5 Sphingomyelins
4.6 Simple glycosphingolipids: mono- and di-hexosylceramides
4.7 Complex glycosphingolipids
4.8 Sphingosines
4.9 Sphingosine-1-phosphates
4.10 Ceramide 1-phosphates
5. Diseases caused by dysregulated sphingolipid metabolism
5.1 Dysregulated sphingolipid anabolism
5.2 Dysregulated sphingolipid catabolism: nonlysosomal degradation
5.3 Dysregulated sphingolipid catabolism: lysosomal degradation
References
CHAPTER 2 Intracellular lipid storage and utilization in adipocytes
Vishva M. Sharma, James M. Ntambi and Vishwajeet Puri
1. Introduction
2. LD-associated protein families
2.1 PAT family of proteins
2.2 CIDE family of proteins
3. Lipid hydrolysis
3.1 Adipose triglyceride lipase
3.2 Hormone-sensitive lipase
3.3 Monoacylglycerol lipase
3.4 ABHD6
4. Other LD-associated proteins
4.1 G0S2
4.2 HIG2
5. Conclusions
References
CHAPTER 3 Metabolic control by lipid droplet proteins
Dilip Menon, Rakesh Mohan Jha, Arpita Nahak and Sheetal Gandotra
1. Lipid droplet coat proteins
2. Proteins involved in lipid synthesis
3. Cytosolic lipases
3.1 Adipose triglycerides lipase
3.2 Hormone sensitive lipase and monoacylglycerols lipase
4. Lysosomal lipolysis
4.1 Autophagosome-mediated macroautophagy
4.2 Chaperone-mediated autophagy
4.3 Microlipophagy/direct lysosome-mediated lipophagy
5. LDemitochondria interaction
6. LDeperoxisome interaction
7. Lipid droplet-endoplasmic reticulum association
8. Expansion, fission, and motility of LDs
9. Transcriptional control of metabolism by LD-localized proteins
References
CHAPTER 4 From endoplasmic reticulum to nucleus: the fate of cellular fatty acids
Antoine Jutras-Carignan, Tania Guillemette and Catherine Mounier
1. Introduction
2. Fatty acids
2.1 Fatty acids uptake
2.2 Fatty acids de novo synthesis
3. De novo synthesis versus beta-oxidation
4. Proteins modification by FA
4.1 Modulation of transcription by FA
4.2 Protein acylation
4.3 Histone acylation
5. Triacylglycerol
5.1 TG uptake
5.2 Synthesis of TG
5.3 TG transport by lipoproteins
5.4 TG storage in lipid droplets
5.5 TG release from LD
6. Phospholipids
6.1 PL uptake
6.2 PL synthesis
6.3 PL metabolism in the nucleus
6.4 PL intracellular distributions
6.5 The fate of FA on PL
6.6 Unsaturated FA-enriched PL in thermogenesis
6.7 Sphingolipids uptake
6.8 Sphingolipids synthesis
6.9 Role of sphingolipids in membrane functions
6.10 Lipids rafts
6.11 CE uptake
6.12 CE trafficking
6.13 CE hydrolysis
7. Conclusion
Abbreviations
References
CHAPTER 5 Lipid trafficking and signaling in adipocytes
Yan Tang and Qi-Qun Tang
1. Lipid droplets in adipocyte
1.1 Lipids
1.2 Lipid transport proteins
2. The development of lipid droplets and adipocytes
2.1 The ER and seipin in LD biogenesis and growth
2.2 LDeLD fusion and CIDE
2.3 LDemitochondrion contacts
3. Developmental origin of adipose tissue
3.1 Transcriptional regulation of adipogenesis
3.2 Adipose stem and progenitor cells
4. Lipid metabolism and signaling
4.1 Fat metabolism between WAT and BAT
4.2 Key signaling lipids for PPARg in adipocytes
4.3 Lipids signaling in adaptive thermogenesis
References
CHAPTER 6 Cell and molecular basis for maintenance of cholesterol homeostasis
Townsend A. Smith and Russell A. DeBose-Boyd
1. Feedback-mediated regulation of cholesterol synthesis
1.1 SREBPs and discovery of SSD
References
CHAPTER 7 Interplay between phospholipid signaling and autophagy
Meenu Maan and Mainak Dutta
1. Introduction
2. Crosstalk between phosphoinositides and mTOR in regulation of autophagy
3. Phosphoinositides and their effectors in autophagy
3.1 Phosphatidylinositol 30-phosphate [PI(3)P]
3.2 PI(3,5)P2
3.3 PI(4)P and PI(4,5)P2
4. Phosphatidic acid and phospholipase D
5. Autophagy regulation by sphingolipids
6. Conclusion
References
CHAPTER 8 The role of cellular lipid metabolism in aging
Xiaoli Chen and Jun Liu
1. Introduction
2. TG storage in LDs and aging
2.1 TG synthesis
2.2 LD biogenesis and growth
2.3 Role of LD in cellular stress and aging
3. TG mobilization and aging
3.1 Intracellular lipolysis
3.2 Mitochondrial FA oxidation
3.3 MitochondriaeLD contacts
3.4 Impact of lipid mobilization and FA oxidation on aging and longevity
4. Deregulation of lipid metabolism during cellular aging
5. Lipid composition changes during cellular senescence
5.1 Triglycerides
5.2 Cholesterol
5.3 Phospholipids
6. Bioactive lipids as senescence SASP factors
6.1 Oxylipins
7. Reprograming of mitochondrial and lipid metabolism in senescent cells
8. Mitochondrial dysfunction in senescence SASP
8.1 Mitochondrial DAMPs
8.2 Pathways that mediate DAMP-induced inflammatory SASP
8.3 Mitochondrial lipids as DAMPs in the SASP
9. Future directions
Acknowledgments
References
CHAPTER 9 Plasma lipid trafficking in type 2 diabetes
Isabella James, Gina Wade, Helaina Von Bank, Ayren McGahee, Autumn Chevalier, Paula Gonzalez, Kayla Bote, James M. Ntambi and Judith Simcox
1. Introduction
2. Methods of plasma lipid measurements
3. Lipid contribution to type 2 diabetes and insulin signaling
3.1 Free fatty acids
3.2 Acylcarnitines
3.3 Diacylglycerols
3.4 Ceramides
4. Perspectives: advances in lipid quantification and mechanisms
References
CHAPTER 10 Lipotoxicity in the pathogenesis of chronic kidney disease complications
Masashi Masuda, Yuji Shiozaki and Makoto Miyazaki
1. Lipotoxicity in kidney diseases and complications of kidney diseases
2. The role of lipids and lipotoxicity in proximal tubular cells
3. Lipotoxicity induces vascular calcification and endoplasmic reticulum stress
4. SFAs induce vascular calcification through ER stress
5. A complex of cyclin-dependent kinase 9/Cyclin T1 mediates SFA-induced ER stress in VSMCs
6. SFAs inhibit autophagy in vascular calcification
7. Conclusion
References
CHAPTER 11 Cellular lipids in the molecular pathogenesis of obesity
Mashudu G. Matumba, Ademola O. Ayeleso, James M. Ntambi and Emmanuel Mukwevho
1. Obesity
1.1 Definition of obesity
1.2 Causes of obesity
2. Diabetes mellitus
2.1 Overview on diabetes
2.2 Causes of type-2 diabetes mellitus
3. Insulin resistance
3.1 Definition of insulin resistance
3.2 Causes of insulin resistance
4. Molecular alterations in obesity, T2DM, and insulin resistance
4.1 Molecular alteration in obesity
4.2 Molecular interaction in T2DM
5. Physical activity, healthy diet, and drugs as an intervention
5.1 Physical activity as intervention
5.2 Healthy diet as an intervention
5.3 Drugs as an intervention
References
CHAPTER 12 Effects of cellular lipids on heart in pathology and physiology
Volodymyr V. Balatskyi, Marcin Wolosiewicz, Aneta M. Dobosz, Zuzanna Tracz-Gaszewska, Adrian Sowka, Maria Kendziorek, Ewelina Krogulec, Viktor O. Navrulin and Pawel Dobrzyn
1. Introduction
2. Fatty acid uptake in the heart
3. Regulation of lipogenesis in the heart
4. Lipolysis and cardiac metabolism
4.1 Cytosolic neutral lipolysis
4.2 Lysosomal acidic lipolysis
5. Fatty acid oxidation and cardiac physiology and pathology
5.1 Oxidative enzymes and their effects on myocardial function
5.2 Fatty acid oxidation, heart failure, and therapeutic strategies
5.3 Effect of fatty acid oxidation on myocardial development
6. Cytotoxic effects of diacylglycerols and ceramides in cardiomyocytes
6.1 Diacylglycerol-dependent cytotoxic signaling in the heart
6.2 Ceramides in cardiac pathology
7. Other sphingolipids and cardiolipin as regulators of heart metabolism
7.1 Sphingolipids
7.2 Cardiolipin
8. Conclusion
Acknowledgments
References
CHAPTER 13 Uncoupling of fat deposition and inflammation during nonalcoholic fatty liver disease
Honggui Li, Xinlei Guo, Eduardo Aquino and Chaodong Wu
1. Introduction
2. NAFLD pathogenesis
2.1 Hepatocyte fat deposition and regulation of fat metabolism
2.2 Pathogenesis of hepatocyte proinflammatory responsys and liver inflammation
2.3 Roles for dysregulation of the adipose-liver axis in NAFLD pathophysiology
2.4 Roles for dysregulation of the gut-liver axis in NAFLD pathophysiology
3. Uncoupling of fat deposition and inflammation during NAFLD pathogenesis
3.1 Glucokinase
3.2 Hepatocyte acyl-CoA: diacylglycerol acyltransferase
3.3 Adipocyte PFKFB3/iPFK2
3.4 Palmitoleate
3.5 ChREBP
3.6 Liver inflammation in the absence of hepatic steatosis
4. Uncoupling of fat deposition and inflammation during NAFLD management
4.1 PPARg
4.2 Polyunsaturated fatty acids
5. Perspective
Acknowledgments
References
CHAPTER 14 Cellular lipids and colorectal cancer
Seong-Ho Lee and Joseph LoBianco
1. Biological aspects of colorectal cancer
1.1 Prevalence and types of CRC
1.2 Cancer hallmarks
1.3 Cancer signaling pathways
2. Lipid metabolism and obesity in the cancer microenvironment
2.1 Impact of obesity in cancer
2.2 Increased de novo synthesis and increased uptake of FAs in cancer cells
2.3 Lipid metabolism enzymes as potential biomarkers of cancer
3. Lipid signaling pathways in CRC and pharmacological/nutraceutical chemoprevention strategy
3.1 The mevalonate/cholesterol biosynthetic pathway and colon cancer
3.2 Eicosanoid signaling and colon cancer
3.3 Ceramide signaling and colon cancer
3.4 Lipidomic signature of CRC
References
CHAPTER 15 Lipid metabolism in neurodegenerative diseases
Jeroen F.J. Bogie, Jeroen Guns and Sam Vanherle
1. Introduction
2. Brain cholesterol
2.1 Homeostatic cholesterol synthesis
2.2 Homeostatic cholesterol transport
2.3 Homeostatic cholesterol turnover
2.4 Cholesterol in Alzheimer’s disease
2.5 Cholesterol in multiple sclerosis
2.6 Cholesterol in Parkinson’s disease
2.7 Cholesterol in Huntington’s disease
3. Brain fatty acids
3.1 Homeostatic fatty acid metabolism in the brain
3.2 Fatty acid chain length and desaturation level in CNS disorders
3.3 Fatty acid synthesis in CNS disorders
3.4 Fatty acid elongation in CNS disorders
3.5 Fatty acid desaturation in CNS disorders
3.6 Fatty acid b-oxidation in CNS disorders
3.7 Fatty acid peroxidation in CNS disorders
4. Conclusions
References
CHAPTER 16 Cellular lipids in B cell immunity, inflammation, and cancer
Yana Zhang, James M. Ntambi and Deyu Fang
1. Introduction
2. Cellular lipids in B cell development and maturation
3. Lipids in B cell activation and plasma cell differentiation
4. Cellular lipid in regulatory B cell differentiation
5. Dysregulated cellular lipid in B cell autoimmune pathogenesis
6. Cellular lipid in B cell dysregulation during allergic disorders
7. Lipids in B cell antitumor immune response
8. Conclusions and perspectives
Acknowledgments
References
CHAPTER 17 Role of cellular fatty acids in combating the corona virus
Abhishek Saxena and Archana Tiwari
1. Introduction
2. EPA and DHA’s helpful effects in preventing COVID-19
3. Fatty acid defense against viral infection
4. Fatty acids antimicrobial activity
5. EPA and DHA’s impact
6. Final thoughts and potential directions for future research
Acknowledgments
References
CHAPTER 18 Cellular lipids and viral infection
Z. Zhang, C. Baguley, X. Wang and B. Kopek
1. Introduction
1.1 Overview of cellular lipids
1.2 Overview of viral replication cycle
2. Attachment and entry
2.1 Role of lipids in virus particle attachment, entry, and uncoating
2.2 Direct fusion
2.3 Raft-dependent macropinocytosis
2.4 Clathrin-mediated endocytosis-cholesterol
2.5 Caveolar endocytosis
2.6 Nonclathrin, noncaveolae, raft-dependent endocytosis
2.7 Lipids as viral fusion cofactors
3. Replication
3.1 Introduction to VRCs
3.2 Phospholipids play critical roles in (þ)RNA virus replication
3.3 Sphingolipids play critical roles in (þ)RNA virus replication
3.4 Sterols play critical roles in (þ)RNA virus replication
3.5 Fatty acids play critical roles in (þ)RNA virus replication
4. Assembly
4.1 Role of lipids in virus particle assembly
4.2 Role of lipids in viral egress/budding
5. Therapeutics
5.1 Drugs the inhibit viral attachment and entry
5.2 Drugs that inhibit viral genome replication
5.3 Drugs that inhibit viral assembly and egress
References
CHAPTER 19 Acetyl-CoA and acetylation in biology and disease
Luigi Puglielli, Michael J. Rigby and Gonzalo Fernandez-Fuente
1. Introduction
2. Biosynthesis and transport of acetyl-CoA
3. Protein acetylation
4. ER acetylation
5. ER acetylation, proteostasis, and metabolic crosstalk
6. Dysfunctional ER acetylation and diseases
7. SLC25A1, SLC13A5, and the citrate/acetyl-CoA pathway
8. ER acetylation and translation
9. Mitochondrial acetylation
9.1 The tricarboxylic acid pathway
9.2 Mitochondria and acetylation
9.3 Mitochondrial morphology
9.4 Mitochondria and diseases
10. Nuclear acetylation
10.1 Transcription factors
10.2 Histone proteins
10.3 Nuclear acetylation and age
11. Cytosolic acetylation
12. O-acetylation of gangliosides
13. Conclusive remarks
References
CHAPTER 20 Role of omega-3 and -6 fatty acids in the inflammatory processes of obesity, hypertension, and autoimmunity
F. Enrique Go´mez, Martha Kaufer-Horwitz, He´ctor Bourges and Gabriela E. Mancera-Chavez
1. Structure, nomenclature, and synthesis of fatty acids
2. Modulation of inflammation by lipid-derived molecules
3. Inflammatory response
4. Antiinflammatory diets
5. Dietary intervention in metabolic diseases
6. Inflammation in metabolic diseases
7. Obesity and inflammation
8. Rheumatic diseases and inflammation
9. Rheumatoid arthritis
10. Systemic lupus erythematosus
11. Sjo¨gren’s syndrome
12. Gout
References
Index
Mariona Rabionet, Robert Engel and Roger Sandhoff
1. Sphingolipids
2. The biological space of sphingolipid structures
2.1 Sphingoid bases
2.2 N-acylation of sphingoid bases
2.3 Headgroup modifications of sphingoid bases and ceramides
2.4 Noncanonical sphingolipids
3. Metabolism of sphingolipids in mammalian cells
3.1 Topology of sphingolipid metabolism
3.2 De novo sphingolipid biosynthesis pathway
3.3 Salvage and sphingomyelinase pathways
3.4 Hydrophilic headgroup modifications of ceramides
4. Physiological functions of sphingolipids
4.1 3-Ketodihydrosphingosines
4.2 Sphinganines
4.3 Dihydroceramides
4.4 Ceramides
4.5 Sphingomyelins
4.6 Simple glycosphingolipids: mono- and di-hexosylceramides
4.7 Complex glycosphingolipids
4.8 Sphingosines
4.9 Sphingosine-1-phosphates
4.10 Ceramide 1-phosphates
5. Diseases caused by dysregulated sphingolipid metabolism
5.1 Dysregulated sphingolipid anabolism
5.2 Dysregulated sphingolipid catabolism: nonlysosomal degradation
5.3 Dysregulated sphingolipid catabolism: lysosomal degradation
References
CHAPTER 2 Intracellular lipid storage and utilization in adipocytes
Vishva M. Sharma, James M. Ntambi and Vishwajeet Puri
1. Introduction
2. LD-associated protein families
2.1 PAT family of proteins
2.2 CIDE family of proteins
3. Lipid hydrolysis
3.1 Adipose triglyceride lipase
3.2 Hormone-sensitive lipase
3.3 Monoacylglycerol lipase
3.4 ABHD6
4. Other LD-associated proteins
4.1 G0S2
4.2 HIG2
5. Conclusions
References
CHAPTER 3 Metabolic control by lipid droplet proteins
Dilip Menon, Rakesh Mohan Jha, Arpita Nahak and Sheetal Gandotra
1. Lipid droplet coat proteins
2. Proteins involved in lipid synthesis
3. Cytosolic lipases
3.1 Adipose triglycerides lipase
3.2 Hormone sensitive lipase and monoacylglycerols lipase
4. Lysosomal lipolysis
4.1 Autophagosome-mediated macroautophagy
4.2 Chaperone-mediated autophagy
4.3 Microlipophagy/direct lysosome-mediated lipophagy
5. LDemitochondria interaction
6. LDeperoxisome interaction
7. Lipid droplet-endoplasmic reticulum association
8. Expansion, fission, and motility of LDs
9. Transcriptional control of metabolism by LD-localized proteins
References
CHAPTER 4 From endoplasmic reticulum to nucleus: the fate of cellular fatty acids
Antoine Jutras-Carignan, Tania Guillemette and Catherine Mounier
1. Introduction
2. Fatty acids
2.1 Fatty acids uptake
2.2 Fatty acids de novo synthesis
3. De novo synthesis versus beta-oxidation
4. Proteins modification by FA
4.1 Modulation of transcription by FA
4.2 Protein acylation
4.3 Histone acylation
5. Triacylglycerol
5.1 TG uptake
5.2 Synthesis of TG
5.3 TG transport by lipoproteins
5.4 TG storage in lipid droplets
5.5 TG release from LD
6. Phospholipids
6.1 PL uptake
6.2 PL synthesis
6.3 PL metabolism in the nucleus
6.4 PL intracellular distributions
6.5 The fate of FA on PL
6.6 Unsaturated FA-enriched PL in thermogenesis
6.7 Sphingolipids uptake
6.8 Sphingolipids synthesis
6.9 Role of sphingolipids in membrane functions
6.10 Lipids rafts
6.11 CE uptake
6.12 CE trafficking
6.13 CE hydrolysis
7. Conclusion
Abbreviations
References
CHAPTER 5 Lipid trafficking and signaling in adipocytes
Yan Tang and Qi-Qun Tang
1. Lipid droplets in adipocyte
1.1 Lipids
1.2 Lipid transport proteins
2. The development of lipid droplets and adipocytes
2.1 The ER and seipin in LD biogenesis and growth
2.2 LDeLD fusion and CIDE
2.3 LDemitochondrion contacts
3. Developmental origin of adipose tissue
3.1 Transcriptional regulation of adipogenesis
3.2 Adipose stem and progenitor cells
4. Lipid metabolism and signaling
4.1 Fat metabolism between WAT and BAT
4.2 Key signaling lipids for PPARg in adipocytes
4.3 Lipids signaling in adaptive thermogenesis
References
CHAPTER 6 Cell and molecular basis for maintenance of cholesterol homeostasis
Townsend A. Smith and Russell A. DeBose-Boyd
1. Feedback-mediated regulation of cholesterol synthesis
1.1 SREBPs and discovery of SSD
References
CHAPTER 7 Interplay between phospholipid signaling and autophagy
Meenu Maan and Mainak Dutta
1. Introduction
2. Crosstalk between phosphoinositides and mTOR in regulation of autophagy
3. Phosphoinositides and their effectors in autophagy
3.1 Phosphatidylinositol 30-phosphate [PI(3)P]
3.2 PI(3,5)P2
3.3 PI(4)P and PI(4,5)P2
4. Phosphatidic acid and phospholipase D
5. Autophagy regulation by sphingolipids
6. Conclusion
References
CHAPTER 8 The role of cellular lipid metabolism in aging
Xiaoli Chen and Jun Liu
1. Introduction
2. TG storage in LDs and aging
2.1 TG synthesis
2.2 LD biogenesis and growth
2.3 Role of LD in cellular stress and aging
3. TG mobilization and aging
3.1 Intracellular lipolysis
3.2 Mitochondrial FA oxidation
3.3 MitochondriaeLD contacts
3.4 Impact of lipid mobilization and FA oxidation on aging and longevity
4. Deregulation of lipid metabolism during cellular aging
5. Lipid composition changes during cellular senescence
5.1 Triglycerides
5.2 Cholesterol
5.3 Phospholipids
6. Bioactive lipids as senescence SASP factors
6.1 Oxylipins
7. Reprograming of mitochondrial and lipid metabolism in senescent cells
8. Mitochondrial dysfunction in senescence SASP
8.1 Mitochondrial DAMPs
8.2 Pathways that mediate DAMP-induced inflammatory SASP
8.3 Mitochondrial lipids as DAMPs in the SASP
9. Future directions
Acknowledgments
References
CHAPTER 9 Plasma lipid trafficking in type 2 diabetes
Isabella James, Gina Wade, Helaina Von Bank, Ayren McGahee, Autumn Chevalier, Paula Gonzalez, Kayla Bote, James M. Ntambi and Judith Simcox
1. Introduction
2. Methods of plasma lipid measurements
3. Lipid contribution to type 2 diabetes and insulin signaling
3.1 Free fatty acids
3.2 Acylcarnitines
3.3 Diacylglycerols
3.4 Ceramides
4. Perspectives: advances in lipid quantification and mechanisms
References
CHAPTER 10 Lipotoxicity in the pathogenesis of chronic kidney disease complications
Masashi Masuda, Yuji Shiozaki and Makoto Miyazaki
1. Lipotoxicity in kidney diseases and complications of kidney diseases
2. The role of lipids and lipotoxicity in proximal tubular cells
3. Lipotoxicity induces vascular calcification and endoplasmic reticulum stress
4. SFAs induce vascular calcification through ER stress
5. A complex of cyclin-dependent kinase 9/Cyclin T1 mediates SFA-induced ER stress in VSMCs
6. SFAs inhibit autophagy in vascular calcification
7. Conclusion
References
CHAPTER 11 Cellular lipids in the molecular pathogenesis of obesity
Mashudu G. Matumba, Ademola O. Ayeleso, James M. Ntambi and Emmanuel Mukwevho
1. Obesity
1.1 Definition of obesity
1.2 Causes of obesity
2. Diabetes mellitus
2.1 Overview on diabetes
2.2 Causes of type-2 diabetes mellitus
3. Insulin resistance
3.1 Definition of insulin resistance
3.2 Causes of insulin resistance
4. Molecular alterations in obesity, T2DM, and insulin resistance
4.1 Molecular alteration in obesity
4.2 Molecular interaction in T2DM
5. Physical activity, healthy diet, and drugs as an intervention
5.1 Physical activity as intervention
5.2 Healthy diet as an intervention
5.3 Drugs as an intervention
References
CHAPTER 12 Effects of cellular lipids on heart in pathology and physiology
Volodymyr V. Balatskyi, Marcin Wolosiewicz, Aneta M. Dobosz, Zuzanna Tracz-Gaszewska, Adrian Sowka, Maria Kendziorek, Ewelina Krogulec, Viktor O. Navrulin and Pawel Dobrzyn
1. Introduction
2. Fatty acid uptake in the heart
3. Regulation of lipogenesis in the heart
4. Lipolysis and cardiac metabolism
4.1 Cytosolic neutral lipolysis
4.2 Lysosomal acidic lipolysis
5. Fatty acid oxidation and cardiac physiology and pathology
5.1 Oxidative enzymes and their effects on myocardial function
5.2 Fatty acid oxidation, heart failure, and therapeutic strategies
5.3 Effect of fatty acid oxidation on myocardial development
6. Cytotoxic effects of diacylglycerols and ceramides in cardiomyocytes
6.1 Diacylglycerol-dependent cytotoxic signaling in the heart
6.2 Ceramides in cardiac pathology
7. Other sphingolipids and cardiolipin as regulators of heart metabolism
7.1 Sphingolipids
7.2 Cardiolipin
8. Conclusion
Acknowledgments
References
CHAPTER 13 Uncoupling of fat deposition and inflammation during nonalcoholic fatty liver disease
Honggui Li, Xinlei Guo, Eduardo Aquino and Chaodong Wu
1. Introduction
2. NAFLD pathogenesis
2.1 Hepatocyte fat deposition and regulation of fat metabolism
2.2 Pathogenesis of hepatocyte proinflammatory responsys and liver inflammation
2.3 Roles for dysregulation of the adipose-liver axis in NAFLD pathophysiology
2.4 Roles for dysregulation of the gut-liver axis in NAFLD pathophysiology
3. Uncoupling of fat deposition and inflammation during NAFLD pathogenesis
3.1 Glucokinase
3.2 Hepatocyte acyl-CoA: diacylglycerol acyltransferase
3.3 Adipocyte PFKFB3/iPFK2
3.4 Palmitoleate
3.5 ChREBP
3.6 Liver inflammation in the absence of hepatic steatosis
4. Uncoupling of fat deposition and inflammation during NAFLD management
4.1 PPARg
4.2 Polyunsaturated fatty acids
5. Perspective
Acknowledgments
References
CHAPTER 14 Cellular lipids and colorectal cancer
Seong-Ho Lee and Joseph LoBianco
1. Biological aspects of colorectal cancer
1.1 Prevalence and types of CRC
1.2 Cancer hallmarks
1.3 Cancer signaling pathways
2. Lipid metabolism and obesity in the cancer microenvironment
2.1 Impact of obesity in cancer
2.2 Increased de novo synthesis and increased uptake of FAs in cancer cells
2.3 Lipid metabolism enzymes as potential biomarkers of cancer
3. Lipid signaling pathways in CRC and pharmacological/nutraceutical chemoprevention strategy
3.1 The mevalonate/cholesterol biosynthetic pathway and colon cancer
3.2 Eicosanoid signaling and colon cancer
3.3 Ceramide signaling and colon cancer
3.4 Lipidomic signature of CRC
References
CHAPTER 15 Lipid metabolism in neurodegenerative diseases
Jeroen F.J. Bogie, Jeroen Guns and Sam Vanherle
1. Introduction
2. Brain cholesterol
2.1 Homeostatic cholesterol synthesis
2.2 Homeostatic cholesterol transport
2.3 Homeostatic cholesterol turnover
2.4 Cholesterol in Alzheimer’s disease
2.5 Cholesterol in multiple sclerosis
2.6 Cholesterol in Parkinson’s disease
2.7 Cholesterol in Huntington’s disease
3. Brain fatty acids
3.1 Homeostatic fatty acid metabolism in the brain
3.2 Fatty acid chain length and desaturation level in CNS disorders
3.3 Fatty acid synthesis in CNS disorders
3.4 Fatty acid elongation in CNS disorders
3.5 Fatty acid desaturation in CNS disorders
3.6 Fatty acid b-oxidation in CNS disorders
3.7 Fatty acid peroxidation in CNS disorders
4. Conclusions
References
CHAPTER 16 Cellular lipids in B cell immunity, inflammation, and cancer
Yana Zhang, James M. Ntambi and Deyu Fang
1. Introduction
2. Cellular lipids in B cell development and maturation
3. Lipids in B cell activation and plasma cell differentiation
4. Cellular lipid in regulatory B cell differentiation
5. Dysregulated cellular lipid in B cell autoimmune pathogenesis
6. Cellular lipid in B cell dysregulation during allergic disorders
7. Lipids in B cell antitumor immune response
8. Conclusions and perspectives
Acknowledgments
References
CHAPTER 17 Role of cellular fatty acids in combating the corona virus
Abhishek Saxena and Archana Tiwari
1. Introduction
2. EPA and DHA’s helpful effects in preventing COVID-19
3. Fatty acid defense against viral infection
4. Fatty acids antimicrobial activity
5. EPA and DHA’s impact
6. Final thoughts and potential directions for future research
Acknowledgments
References
CHAPTER 18 Cellular lipids and viral infection
Z. Zhang, C. Baguley, X. Wang and B. Kopek
1. Introduction
1.1 Overview of cellular lipids
1.2 Overview of viral replication cycle
2. Attachment and entry
2.1 Role of lipids in virus particle attachment, entry, and uncoating
2.2 Direct fusion
2.3 Raft-dependent macropinocytosis
2.4 Clathrin-mediated endocytosis-cholesterol
2.5 Caveolar endocytosis
2.6 Nonclathrin, noncaveolae, raft-dependent endocytosis
2.7 Lipids as viral fusion cofactors
3. Replication
3.1 Introduction to VRCs
3.2 Phospholipids play critical roles in (þ)RNA virus replication
3.3 Sphingolipids play critical roles in (þ)RNA virus replication
3.4 Sterols play critical roles in (þ)RNA virus replication
3.5 Fatty acids play critical roles in (þ)RNA virus replication
4. Assembly
4.1 Role of lipids in virus particle assembly
4.2 Role of lipids in viral egress/budding
5. Therapeutics
5.1 Drugs the inhibit viral attachment and entry
5.2 Drugs that inhibit viral genome replication
5.3 Drugs that inhibit viral assembly and egress
References
CHAPTER 19 Acetyl-CoA and acetylation in biology and disease
Luigi Puglielli, Michael J. Rigby and Gonzalo Fernandez-Fuente
1. Introduction
2. Biosynthesis and transport of acetyl-CoA
3. Protein acetylation
4. ER acetylation
5. ER acetylation, proteostasis, and metabolic crosstalk
6. Dysfunctional ER acetylation and diseases
7. SLC25A1, SLC13A5, and the citrate/acetyl-CoA pathway
8. ER acetylation and translation
9. Mitochondrial acetylation
9.1 The tricarboxylic acid pathway
9.2 Mitochondria and acetylation
9.3 Mitochondrial morphology
9.4 Mitochondria and diseases
10. Nuclear acetylation
10.1 Transcription factors
10.2 Histone proteins
10.3 Nuclear acetylation and age
11. Cytosolic acetylation
12. O-acetylation of gangliosides
13. Conclusive remarks
References
CHAPTER 20 Role of omega-3 and -6 fatty acids in the inflammatory processes of obesity, hypertension, and autoimmunity
F. Enrique Go´mez, Martha Kaufer-Horwitz, He´ctor Bourges and Gabriela E. Mancera-Chavez
1. Structure, nomenclature, and synthesis of fatty acids
2. Modulation of inflammation by lipid-derived molecules
3. Inflammatory response
4. Antiinflammatory diets
5. Dietary intervention in metabolic diseases
6. Inflammation in metabolic diseases
7. Obesity and inflammation
8. Rheumatic diseases and inflammation
9. Rheumatoid arthritis
10. Systemic lupus erythematosus
11. Sjo¨gren’s syndrome
12. Gout
References
Index
- Edition: 1
- Published: August 3, 2023
- No. of pages (Hardback): 556
- Imprint: Academic Press
- Language: English
- Hardback ISBN: 9780443218224
- eBook ISBN: 9780323955836
JN
James Mukasa Ntambi
Dr. James M. Ntambi is a Professor of Biochemistry and the Steenbock Professor of Nutritional Sciences, at the University of Wisconsin-Madison, as well as an Adjunct Professor of Biological Chemistry at Johns Hopkins University School of Medicine. The focus of Dr. Ntambi’s research is to understand the genetic regulation of metabolism, adipocyte biology, and differentiation. He is specifically interested in the genetic basis of obesity, cardiovascular disease, insulin resistance, and diabetes and how dietary factors, hormones, and environmental factors influence these disease states. Recently, his team has genetically engineered mice that are born without the stearoyl-CoA desaturase gene-1, and found that these mice resist obesity, diabetes, and fatty liver disease. Most recent work has focused on the role monounsaturated fatty acids in diet induced de novo lipogenesis, obesity, and insulin resistance. Dr. Ntambi also conducts research on obesity and diabetes and other noncommunicable metabolic diseases in developing countries. Dr. Ntambi has published more than 230 scientific articles in such journals including Journal of Biological Chemistry, Journal of Lipid Research, PNAS, Science, Cell Metabolism, Hepatology journal, BBRC, JCI, BBA, PLoS, Journal of Nutrition, and American Journal of Physiology-Endocrinology and Metabolism, among others.
Affiliations and expertise
Department of Biochemistry, Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USARead Cellular Lipid in Health and Disease on ScienceDirect