Liver innate immune cells and insulin resistance: the multiple facets of Kupffer cells
Abstract
Obesity, which affects 600 million adults worldwide, is a major risk factor for type 2 diabetes (T2D) and insulin resistance. Current therapies for these metabolic disorders include weight management by lifestyle intervention or bariatric surgery and pharmacological treatment with the aim of regulating blood glucose. Probably because of their short‐term effectiveness, these therapies have not been able to stop the rapidly rising prevalence of T2D over the past decades, highlighting an urgent need to develop new therapeutic strategies. The role of immune cells, such as macrophages, in insulin resistance has been extensively studied. Major advances have been made to elucidate the role of adipose tissue macrophages in these pathogeneses. Recently, anti‐inflammatory drugs have been suggested as an alternative treatment for T2D, and clinical trials of these agents are currently ongoing. In addition, results of previous clinical trials using antibodies against inflammatory cytokines, which showed modest effects, are now being rigorously re‐evaluated. However, it is still unclear how liver macrophages [termed Kupffer cells (KCs)], which constitute the major source of macrophages in the body, contribute to the development of insulin resistance. In this review, we will discuss the present understanding of the role of liver immune cells in the development of insulin resistance. We will particularly focus on KCs, which could represent an attractive target for the treatment of metabolic diseases.
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Kupffer cells make up as much as 15% of liver cells and 80-90% of tissue-resident macrophages.
“Liver-resident macrophages, known as Kupffer cells, comprise up to 15% of total liver cells and 80–90% of all tissue-resident macrophages53.”
From Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages (2020) · cites this paper as [53]
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- Authors
- Jager, J., Aparicio‐Vergara, M., & Aouadi, M.
- Affiliations
- Karolinska University Hospital (SE)
- Department of Medicine KI/AZ Integrated CardioMetabolic Center Karolinska Institutet at Karolinska University Hospital Huddinge C2‐84, S‐141 86 Stockholm Sweden
- Corresponding author
- Aouadi, M.
- ORCID
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2016-02-11
- Volume
- 280
- Issue
- 2
- Pages
- 209-220
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- OpenAlex
- W2262478237
- Cited by
- 90
- References
- 108
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 2 · 2023: 11 · 2022: 7 · 2021: 6 · 2020: 20 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 7
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Center
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- Kupffer cells, insulin resistance, type 2 diabetes, obesity, hepatic macrophages, anti-inflammatory therapy, metabolic disease treatment
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Hepatitis, Humans, Insulin Resistance, Kupffer Cells, Liver, Obesity, Hepatocytes
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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