Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
Open accessAbstract
Acquired resistance to the action of insulin to stimulate glucose transport in skeletal muscle is associated with obesity and promotes the development of type 2 diabetes. In skeletal muscle, insulin resistance can result from high levels of circulating fatty acids that disrupt insulin signalling pathways. However, the severity of insulin resistance varies greatly among obese people. Here we postulate that this variability might reflect differences in levels of lipid-droplet proteins that promote the sequestration of fatty acids within adipocytes in the form of triglycerides, thereby lowering exposure of skeletal muscle to the inhibitory effects of fatty acids.
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TNF-α inhibits both the insulin and catecholamine signaling pathways in adipocytes, resulting in decreased metabolic flexibility.
“TNF-α inhibits both the insulin and the catecholamine signaling pathways in adipocytes, resulting in decreased metabolic flexibility”
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Weight gain and loss correlate with decreasing and increasing insulin sensitivity, respectively.
“Studies indicate that weight gain and loss correlate with decreasing and increasing insulin sensitivity, respectively.10”
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These events cause insulin resistance in adipocytes, exacerbation of the inflammatory state, and systemic insulin resistance.
“These events cause insulin resistance in adipocytes, exacerbation of the inflammatory state, and systemic insulin resistance ([59](#B59), [147](#B147))”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [59]
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- Authors
- Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Czech, Michael P.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2008-05
- Volume
- 9
- Issue
- 5
- Pages
- 367-377
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC2886982
- OpenAlex
- W2012037560
- Cited by
- 2,292
- References
- 144
- Citations by year
- 2026: 66 · 2025: 104 · 2024: 119 · 2023: 124 · 2022: 137 · 2021: 149 · 2020: 156 · 2019: 144 · 2018: 153 · 2017: 151 · 2016: 174 · 2015: 155 · 2014: 127 · 2013: 117 · 2012: 99
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK030898, DK 32520, R37DK030898, DK030648, DK030898, P30DK032520, R01DK030648)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- adipocyte dysfunction, obesity, insulin resistance, type 2 diabetes, fatty acids, lipid droplets, lipid homeostasis, glucose homeostasis, skeletal muscle, insulin signaling, circulating fatty acids
- MeSH terms
- Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin, Insulin Resistance, Lipolysis, Mitochondria, Obesity, Triglycerides, Tumor Necrosis Factor-alpha, Signal Transduction, Adipocytes, Muscle, Skeletal, PPAR gamma
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