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Cited by 1,575Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Adipose tissue dysfunction as determinant of obesity-associated metabolic complications

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Longo, Michele, Zatterale, Federica, Naderi, Jamal, Parrillo, Luca, Formisano, Pietro, Raciti, Gregory Alexander, Beguinot, Francesco, Miele, Claudia·2019·International Journal of Molecular Sciences
DOI 10.3390/ijms20092358PMC PMC6539070
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Abstract

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.

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  • Prolonged obesity leads to pathological changes and dysfunction in adipose tissue, characterized by disrupted lipid metabolism, impaired insulin signaling, inflammation, and cell death, which are critical precursors to type 2 diabetes and other metabolic diseases.

    “However, prolonged obesity leads to pathological changes and dysfunction in adipose tissue, characterized by disrupted lipid metabolism, impaired insulin signaling, inflammation, and cell death. These changes are critical precursors to the onset of type 2 diabetes and other metabolic diseases (Longo et al., 2019).”

    From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Longo et al., 2019

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Cited by

Sorted by citations

Authors
Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G. A., Beguinot, F., & Miele, C.
Affiliations
  • Institute for Experimental Endocrinology and Oncology (IT)
  • Department of Translational Medicine, Federico II University of Naples, 80131 Naples, Italy
Corresponding author
Miele, Claudia
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-05-13
Volume
20
Issue
9
Pages
2358
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms20092358
PMC
PMC6539070
OpenAlex
W2944549000
Cited by
1,575
References
29
Citations by year
2026: 151 · 2025: 249 · 2024: 273 · 2023: 284 · 2022: 264 · 2021: 211 · 2020: 122 · 2019: 18 · 2012: 1
FWCI
22.44
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
European Commission (665403)
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
obesity, type 2 diabetes, insulin resistance, metabolically unhealthy obesity, subcutaneous adipose tissue, adipocyte hypertrophy, adipocyte hyperplasia, ectopic fat deposition, lipotoxicity, visceral adipose tissue, low-grade inflammation, energy homeostasis
MeSH terms
Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin Resistance, Obesity, Subcutaneous Fat, Adipogenesis

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