Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome — An allostatic perspective
Abstract
While the link between obesity and type 2 diabetes is clear on an epidemiological level, the underlying mechanism linking these two common disorders is not as clearly understood. One hypothesis linking obesity to type 2 diabetes is the adipose tissue expandability hypothesis. The adipose tissue expandability hypothesis states that a failure in the capacity for adipose tissue expansion, rather than obesity per se is the key factor linking positive energy balance and type 2 diabetes. All individuals possess a maximum capacity for adipose expansion which is determined by both genetic and environmental factors. Once the adipose tissue expansion limit is reached, adipose tissue ceases to store energy efficiently and lipids begin to accumulate in other tissues. Ectopic lipid accumulation in non-adipocyte cells causes lipotoxic insults including insulin resistance, apoptosis and inflammation. This article discusses the links between adipokines, inflammation, adipose tissue expandability and lipotoxicity. Finally, we will discuss how considering the concept of allostasis may enable a better understanding of how diabetes develops and allow the rational design of new anti diabetic treatments.
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Dysfunctional adipose tissue promotes systemic low-grade inflammation, fat overflow, and ectopic lipid deposition, which further contributes to insulin resistance.
“Evidence suggests that dysfunctional AT promotes systemic low-grade inflammation, fat overflow, and, hence, ectopic lipid deposition, which further contributes to insulin resistance (Virtue and Vidal-Puig, 2010).”
From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Virtue and Vidal-Puig, 2010
Excessive abdominal fat is associated with adipose tissue dysfunction, leading to systemic low-grade inflammation, fat overflow, ectopic lipid deposition, and reduced insulin sensitivity.
“Excessive abdominal fat is associated with adipose tissue dysfunction, leading to systemic low-grade inflammation, fat overflow, ectopic lipid deposition, and reduced insulin sensitivity.”
From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Virtue and Vidal-Puig, 2010
Under excess caloric intake, white adipose tissue reaches its upper limit for further lipid storage.
“In fact, under excess caloric intake, WAT reaches its upper limit for further lipid storage ([157](#B157), [169](#B169)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [169]
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- Authors
- Virtue, S., & Vidal-Puig, A.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Virtue, Sam
- ORCID
- Virtue, Sam
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 1801
- Issue
- 3
- Pages
- 338-349
- ISSN
- 1388-1981 (ISSN-L)
- OpenAlex
- W2035489548
- Semantic Scholar
- 470ac3b56b5b657fa79061f68dcdb8d8593fc4e8
- Cited by
- 1,013
- References
- 80
- Citations by year
- 2026: 58 · 2025: 65 · 2024: 49 · 2023: 46 · 2022: 68 · 2021: 62 · 2020: 52 · 2019: 68 · 2018: 77 · 2017: 75 · 2016: 64 · 2015: 66 · 2014: 68 · 2013: 76 · 2012: 69
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Diabetes UK
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/E011950/1)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- adipose tissue expandability, lipotoxicity, metabolic syndrome, obesity, type 2 diabetes, allostasis, ectopic fat deposition, insulin resistance, adipokines, inflammation, apoptosis, diabetes treatment
- MeSH terms
- Adipose Tissue, Animals, Cell Differentiation, Diabetes Mellitus, Humans, Insulin Resistance, Liver, Models, Biological, Neovascularization, Pathologic, Adipocytes, Metabolic Syndrome, Lipid Metabolism, Insulin-Secreting Cells, Allostasis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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