ArticleThe Journal of clinical investigation2025
Caloric restriction promotes resolution of atherosclerosis in obese mice, while weight regain accelerates its progression.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- Trained immunity: new paradigm in the immunological memory of cardiovascular disease.ImmunoHorizons · 2026Review
- Interferon-sensitized hematopoietic progenitors dynamically alter organismal immunity.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- Influence of Weight Loss and Weight Regain on Adipose Tissue Inflammation.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Platelets impair the resolution of inflammation in atherosclerotic plaques in insulin-resistant mice after lipid lowering.JCI insight · 2025Article
- IL1β Secretion by Epididymal White Adipose Tissue Macrophages Regulates Myelopoiesis and Plaque Inflammation in Obese Mice and in Caloric Restriction.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Inflammation in atherosclerosis: a Big Idea that has underperformed so far.Current opinion in lipidology · 2025Review
- The role of immune cells-mediated memory in weight cycling, glucose disorders and insulin resistance.Frontiers in immunology · 2025Review
- Obesity Duration and Cardiometabolic Disease.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
While weight loss is highly recommended for those with obesity, >60% regain their lost weight. This weight cycling is associated with an elevated risk of cardiovascular disease, relative to never having lost weight. How weight loss and regain directly influence atherosclerotic inflammation is unknown. Thus, we studied short-term caloric restriction (stCR) in obese hypercholesterolemic mice, without confounding effects from changes in diet composition. Weight loss promoted atherosclerosis resolution independent of plasma cholesterol. Single-cell RNA sequencing and subsequent mechanistic studies indicated that this can be partly attributed to a unique subset of macrophages accumulating with stCR in epididymal white adipose tissue (eWAT) and atherosclerotic plaques. These macrophages, distinguished by high expression of Fc γ receptor 4 (Fcgr4), helped to clear necrotic cores in atherosclerotic plaques. Conversely, weight regain (WR) following stCR accelerated atherosclerosis progression with disappearance of Fcgr4+ macrophages from eWAT and plaques. Furthermore, WR caused reprogramming of immune progenitors, sustaining hyperinflammatory responsiveness. In summary, we have developed a model to investigate the inflammatory effects of weight cycling on atherosclerosis and the interplay between adipose tissue, bone marrow, and plaques. The findings suggest potential approaches to promote atherosclerosis resolution in obesity and weight cycling through induction of Fcgr4+ macrophages and inhibition of immune progenitor reprogramming.
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Registered trials
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