The DOI matches its Crossref record; 183 of the 184 references it cites were found in a registry or an index.
What Is Lipotoxicity?
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
Citations
Cites
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Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
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Cellular mechanisms of insulin resistance
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The mitochondrial permeability transition pore and its role in cell death
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Cited by
Sorted by citations
Arroyave-Ospina, J. C., Wu, Z., Geng, Y., & Moshage, H. J. (2021) · Antioxidants · doi:10.3390/antiox10020174 · Cited by 560
Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476
Qi, J., Kim, J.-W., Zhou, Z., Lim, C.-W., & Kim, B. (2020) · The American Journal of Pathology · doi:10.1016/j.ajpath.2019.09.011 · Cited by 338
Zhang, S., Peng, X., Yang, S., Li, X., Huang, M., Wei, S., Liu, J., He, G., Zheng, H., Yang, L., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04593-3 · Cited by 335
Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes
Sobczak, A. I. S., Blindauer, C. A., & Stewart, A. J. (2019) · Nutrients · doi:10.3390/nu11092022 · Cited by 314
Metadata
- 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
- 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
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Physiology (medical) › 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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