What is lipotoxicity?

Engin, Ayse Basak

doi:10.1007/978-3-319-48382-5_8

Cited by 260Adipokines, Inflammation, and Metabolic DiseasesLipid metabolism and biosynthesisAdipose Tissue and Metabolism

What is lipotoxicity?

Engin, Ayse Basak·2017·Advances in experimental medicine and biology

DOI 10.1007/978-3-319-48382-5_8

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Abstract

Enlarged fat cells in obese adipose tissue diminish capacity to store fat and are resistant to the anti-lipolytic effect of insulin. Insulin resistance (IR)-associated S-nitrosylation of insulin-signaling proteins increases in obesity. In accordance with the inhibition of insulin-mediated anti-lipolytic action, plasma free fatty acid (FFA) levels increase. Additionally, endoplasmic reticulum stress stimuli induce lipolysis by activating cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) and extracellular signal-regulated kinase ½ (ERK1/2) signaling in adipocytes. Failure of packaging of excess lipid into lipid droplets causes chronic elevation of circulating fatty acids, which can reach to toxic levels within non-adipose tissues. Deleterious effects of lipid accumulation in non-adipose tissues are known as lipotoxicity. In fact, triglycerides may also serve a storage function for long-chain non-esterified fatty acids and their products such as ceramides and diacylglycerols (DAGs). Thus, excess DAG, ceramide and saturated fatty acids in obesity can induce chronic inflammation and have harmful effect on multiple organs and systems. In this context, chronic adipose tissue inflammation, mitochondrial dysfunction and IR have been discussed within the scope of lipotoxicity.

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During obesity, excessive accumulation of triglycerides in adipocytes leads to cellular and organelle dysfunction.
“Indeed, during obesity, excessive accumulation of triglycerides in adipocytes leads to cellular and organelle dysfunction [230,231].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [231]
Oxidative stress is usually observed in adipocytes during obesity.
“Oxidative stress is usually observed in adipocytes during obesity.”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [231]
Ectopic deposition of lipids in muscle is associated with inflammation, oxidative injury, insulin resistance and disruption of several cell functions, a condition referred to as lipotoxicity.
“This ectopic deposition of lipids in muscle is a hallmark of pathology in several conditions and is associated with inflammation, oxidative injury, insulin resistance and disruption of several cell functions, a condition referred to as lipotoxicity [55–57].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [55]
Excess ectopic lipids are believed to induce lipotoxicity that can impair neuromuscular function.
“These excess ectopic lipids are believed to induce lipotoxicity, where dysfunctional lipid metabolism promotes inflammation, oxidative injury and disruption of several cell functions, including maintenance of the neuromuscular junction (NMJ) [55–57, 64], all of which could impair neuromuscular function.”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [55]
Obesity may induce brain insulin resistance through mechanisms including adipose tissue inability to store fatty acids leading to their accumulation in brain, pro-inflammatory macrophages producing cytokines that cross the blood-brain barrier and induce central inflammation, and nutrient overload causing mitochondrial dysfunction and oxidative stress.
“Obesity may induce brain insulin resistance through several mechanisms: 1) in obesity conditions the adipose tissue loses its ability to store fatty acids, thereby inducing their accumulation in other tissues including the brain, which consequently develop insulin resistance (Engin, 2017); 2) in the adipose tissue of obese people, macrophages become pro-inflammatory and produce inflammatory”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Engin, 2017

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White Adipose Tissue Dysfunction: Pathophysiology and Emergent Measurements
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Link between Insulin Resistance and Obesity—From Diagnosis to Treatment
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Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head
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Hexanoic, Octanoic and Decanoic Acids Promote Basal and Insulin-Induced Phosphorylation of the Akt-mTOR Axis and a Balanced Lipid Metabolism in the HepG2 Hepatoma Cell Line
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Altered Metabolic Profile and Adipocyte Insulin Resistance Mark Severe Liver Fibrosis in Patients with Chronic Liver Disease
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Long-term administration of Western diet induced metabolic syndrome in mice and causes cardiac microvascular dysfunction, cardiomyocyte mitochondrial damage, and cardiac remodeling involving caveolae and caveolin-1 expression
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Authors: Engin, A. B.
Venue: Advances in experimental medicine and biology
Publisher: Springer International Publishing
Published: 2017
Volume: 960
Pages: 197-220
ISSN: 0065-2598 (ISSN-L)
2214-8019
DOI: 10.1007/978-3-319-48382-5_8
OpenAlex: W2623539005
Cited by: 260
References: 184
Citations by year: 2026: 9 · 2025: 32 · 2024: 35 · 2023: 38 · 2022: 44 · 2021: 40 · 2020: 24 · 2019: 24 · 2018: 12 · 2017: 2
FWCI: 74.41
Type: book chapter
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Advances in experimental medicine and biology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords: lipotoxicity, obesity, insulin resistance, adipocytes, lipolysis, S-nitrosylation, free fatty acids, endoplasmic reticulum stress, cAMP/PKA signaling, ERK signaling, lipid droplets, diacylglycerol, ceramide, chronic inflammation, mitochondrial dysfunction
MeSH terms: Adipose Tissue, Animals, Humans, Inflammation, Insulin Resistance, Lipids, Mitochondria, Obesity, Adipocytes

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