Lipid signaling and lipotoxicity in metaflammation: indications for metabolic disease pathogenesis and treatment

Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes or as signaling molecules that regulate metabolic homeostasis through many mechani...

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Published inJournal of lipid research Vol. 57; no. 12; pp. 2099 - 2114
Main Authors Ertunc, Meric Erikci, Hotamisligil, Gökhan S.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.12.2016
The American Society for Biochemistry and Molecular Biology
Elsevier
SeriesThematic Review Series: Lipotoxicity: Many Roads to Cell Dysfunction and Cell Death
Subjects
Adipose Tissue - metabolism
Adipose Tissue - pathology
Animals
diabetes
Energy Metabolism
Humans
inflammation
Inflammation Mediators - metabolism
Insulin Resistance
Lipid Metabolism
lipids
Liver - immunology
Liver - metabolism
Metabolic Diseases - immunology
Metabolic Diseases - metabolism
Muscle, Skeletal - metabolism
obesity
signaling lipids
Stress, Physiological
Thematic Review Series
lipids
signaling lipids
inflammation
diabetes
insulin resistance
obesity
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Abstract Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes or as signaling molecules that regulate metabolic homeostasis through many mechanisms. Cells possess an integrated set of response systems to adapt to stresses such as those imposed by nutrient fluctuations during feeding-fasting cycles. While lipids are pivotal for these homeostatic processes, they can also contribute to detrimental metabolic outcomes. When metabolic stress becomes chronic and adaptive mechanisms are overwhelmed, as occurs during prolonged nutrient excess or obesity, lipid influx can exceed the adipose tissue storage capacity and result in accumulation of harmful lipid species at ectopic sites such as liver and muscle. As lipid metabolism and immune responses are highly integrated, accumulation of harmful lipids or generation of signaling intermediates can interfere with immune regulation in multiple tissues, causing a vicious cycle of immune-metabolic dysregulation. In this review, we summarize the role of lipotoxicity in metaflammation at the molecular and tissue level, describe the significance of anti-inflammatory lipids in metabolic homeostasis, and discuss the potential of therapeutic approaches targeting pathways at the intersection of lipid metabolism and immune function.
AbstractList Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes or as signaling molecules that regulate metabolic homeostasis through many mechanisms. Cells possess an integrated set of response systems to adapt to stresses such as those imposed by nutrient fluctuations during feeding-fasting cycles. While lipids are pivotal for these homeostatic processes, they can also contribute to detrimental metabolic outcomes. When metabolic stress becomes chronic and adaptive mechanisms are overwhelmed, as occurs during prolonged nutrient excess or obesity, lipid influx can exceed the adipose tissue storage capacity and result in accumulation of harmful lipid species at ectopic sites such as liver and muscle. As lipid metabolism and immune responses are highly integrated, accumulation of harmful lipids or generation of signaling intermediates can interfere with immune regulation in multiple tissues, causing a vicious cycle of immune-metabolic dysregulation. In this review, we summarize the role of lipotoxicity in metaflammation at the molecular and tissue level, describe the significance of anti-inflammatory lipids in metabolic homeostasis, and discuss the potential of therapeutic approaches targeting pathways at the intersection of lipid metabolism and immune function.
Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes or as signaling molecules that regulate metabolic homeostasis through many mechanisms. Cells possess an integrated set of response systems to adapt to stresses such as those imposed by nutrient fluctuations during feeding-fasting cycles. While lipids are pivotal for these homeostatic processes, they can also contribute to detrimental metabolic outcomes. When metabolic stress becomes chronic and adaptive mechanisms are overwhelmed, as occurs during prolonged nutrient excess or obesity, lipid influx can exceed the adipose tissue storage capacity and result in accumulation of harmful lipid species at ectopic sites such as liver and muscle. As lipid metabolism and immune responses are highly integrated, accumulation of harmful lipids or generation of signaling intermediates can interfere with immune regulation in multiple tissues, causing a vicious cycle of immune-metabolic dysregulation. In this review, we summarize the role of lipotoxicity in metaflammation at the molecular and tissue level, describe the significance of anti-inflammatory lipids in metabolic homeostasis, and discuss the potential of therapeutic approaches targeting pathways at the intersection of lipid metabolism and immune function.Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes or as signaling molecules that regulate metabolic homeostasis through many mechanisms. Cells possess an integrated set of response systems to adapt to stresses such as those imposed by nutrient fluctuations during feeding-fasting cycles. While lipids are pivotal for these homeostatic processes, they can also contribute to detrimental metabolic outcomes. When metabolic stress becomes chronic and adaptive mechanisms are overwhelmed, as occurs during prolonged nutrient excess or obesity, lipid influx can exceed the adipose tissue storage capacity and result in accumulation of harmful lipid species at ectopic sites such as liver and muscle. As lipid metabolism and immune responses are highly integrated, accumulation of harmful lipids or generation of signaling intermediates can interfere with immune regulation in multiple tissues, causing a vicious cycle of immune-metabolic dysregulation. In this review, we summarize the role of lipotoxicity in metaflammation at the molecular and tissue level, describe the significance of anti-inflammatory lipids in metabolic homeostasis, and discuss the potential of therapeutic approaches targeting pathways at the intersection of lipid metabolism and immune function.
Author Hotamisligil, Gökhan S.
Ertunc, Meric Erikci
Author_xml – sequence: 1
  givenname: Meric Erikci
  surname: Ertunc
  fullname: Ertunc, Meric Erikci
– sequence: 2
  givenname: Gökhan S.
  surname: Hotamisligil
  fullname: Hotamisligil, Gökhan S.
  email: ghotamis@hsph.harvard.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27330055$$D View this record in MEDLINE/PubMed
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Issue 12
Keywords lipids
signaling lipids
inflammation
diabetes
insulin resistance
obesity
Language English
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Present address of M. Erikci Ertunc: Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037.
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Snippet Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient...
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SubjectTerms Adipose Tissue - metabolism
Adipose Tissue - pathology
Animals
diabetes
Energy Metabolism
Humans
inflammation
Inflammation Mediators - metabolism
Insulin Resistance
Lipid Metabolism
lipids
Liver - immunology
Liver - metabolism
Metabolic Diseases - immunology
Metabolic Diseases - metabolism
Muscle, Skeletal - metabolism
obesity
signaling lipids
Stress, Physiological
Thematic Review Series
Title Lipid signaling and lipotoxicity in metaflammation: indications for metabolic disease pathogenesis and treatment
URI https://dx.doi.org/10.1194/jlr.R066514
https://www.ncbi.nlm.nih.gov/pubmed/27330055
https://www.proquest.com/docview/1826706240
https://pubmed.ncbi.nlm.nih.gov/PMC5321214
https://doaj.org/article/405b696f45d34bb19e08d8a31f848549
Volume 57
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