ArticleThe Journal of clinical investigation2023
Reduction of SPARC protects mice against NLRP3 inflammasome activation and obesity.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00427193 (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy), which is not on this map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE)
Who cites it
27 citing papers in PubMed, 25 citations in OpenAlex.
- Caloric restriction attenuates NLRP3 inflammasome activation and oxidative stress in leukocytes of patients with obesity.iScience · 2026Article
- Endothelial cell-microglia crosstalk mediates heart failure-associated synaptic loss and cognitive impairment in male mice.Nature communications · 2026Article
- Exercise preserves β-cell function in type 2 diabetes by reshaping intra-islet macrophage-β-cell crosstalk.Life metabolism · 2026Article
- Exercise-induced myokines in metabolic regulation: mechanisms, mimetics, and translational potential.Archives of pharmacal research · 2026Review
- Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging.Nature aging · 2026Article
- Predictive value of 1-hour postprandial SPARC levels on metabolic outcomes from Mediterranean diet adherence: results from a randomized controlled feeding study.Life metabolism · 2026Article
- The m5C orchestrator NSUN7 drives SPARC/HMGB1 axis-mediated inflammation to exacerbate kidney injury.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Low protein-induced-FGF-21 signaling remodels adipose tissue on reduced markers of senescence during aging.GeroScience · 2026Article
- NLR inflammasome pathways: key targets for pathogenesis and therapy of metabolic diseases.Frontiers in immunology · 2026Review
- Targeting macrophage metabolism: mechanisms, cellular crosstalk and implications in obesity-associated metabolic diseases.Frontiers in immunology · 2026Review
- Adipose immune microenvironment: catalyst of age-related adipose tissue dysfunction.Immunity & ageing : I & A · 2025Review
- Exploring the Role of SPARC in Atherosclerosis: Mechanisms and Potential Implications.Current atherosclerosis reports · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Metabolic regulation of immunological aging.Nature aging · 2025Review
- Comprehensive analysis of keloid super-enhancer networks reveals FOXP1-mediated anti-senescence mechanisms in fibrosis.Cellular & molecular biology letters · 2025Article
- Muscle in Endocrinology: From Skeletal Muscle Hormone Regulation to Myokine Secretion and Its Implications in Endocrine-Metabolic Diseases.Journal of clinical medicine · 2025Review
- Microglial repopulation reverses radiation-induced cognitive dysfunction by restoring medial prefrontal cortex activity and modulating leukotriene-C4 synthesis.Acta neuropathologica communications · 2025Article
- A Single Intraperitoneal Secreted Protein Acidic and Rich in Cysteine Injection in Mice Is Towards an Exercise-like Phenotype.Biology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The comprehensive assessment of long-term effects of reducing intake of energy (CALERIE-II; NCT00427193) clinical trial established that caloric restriction (CR) in humans lowers inflammation. The identity and mechanism of endogenous CR-mimetics that can be deployed to control obesity-associated inflammation and diseases are not well understood. Our studies have found that 2 years of 14% sustained CR in humans inhibits the expression of the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), in adipose tissue. In mice, adipose tissue remodeling caused by weight loss through CR and low-protein diet feeding decreased, while high-fat diet-induced (HFD-induced) obesity increased SPARC expression in adipose tissue. Inducible SPARC downregulation in adult mice mimicked CR's effects on lowering adiposity by regulating energy expenditure. Deletion of SPARC in adipocytes was sufficient to protect mice against HFD-induced adiposity, chronic inflammation, and metabolic dysfunction. Mechanistically, SPARC activates the NLRP3 inflammasome at the priming step and downregulation of SPARC lowers macrophage inflammation in adipose tissue, while excess SPARC activated macrophages via JNK signaling. Collectively, reduction of adipocyte-derived SPARC confers CR-like metabolic and antiinflammatory benefits in obesity by serving as an immunometabolic checkpoint of inflammation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.