Adipose Tissue Immunometabolism: Unveiling the Intersection of Metabolic and Immune Regulation.

UNASSIGNED: Excess body weight has become a global epidemic and a significant risk factor for developing chronic diseases, which are the leading causes of worldwide morbidities. Adipose tissue (AT), primarily composed of adipocytes, stores substantial amounts of energy and plays a crucial role in maintaining whole-body glucose and lipid metabolism. This helps prevent excessive body fat accumulation and lipotoxicity in peripheral tissues. In addition, AT contains endothelial cells and a substantial population of immune cells (constituting 60-70% of non-adipocyte cells), including macrophages, T and B lymphocytes, and natural killer cells. These resident immune cells engage in crosstalk with adipocytes, contributing to the maintenance of metabolic and immune homeostasis in AT. An exacerbated inflammatory response or inadequate immune resolution can lead to chronic systemic low-grade inflammation, triggering the development of metabolic alterations and the onset of chronic diseases. This review aims to elucidate the regulatory mechanisms through which immune cells influence AT function and energy homeostasis. We also focus on the interactions and functional dynamics of immune cell populations, highlighting their role in maintaining the delicate balance between metabolic health and obesity-related inflammation. Finally, understanding immunometabolism is crucial for unraveling the pathogenesis of metabolic diseases and developing targeted immunotherapeutic strategies. These strategies may offer innovative avenues in the rapidly evolving field of immunometabolism. (Rev Invest Clin. 2024;76(2):65-79).

Adipose Tissue Immunometabolism: Unveiling the Intersection of Metabolic and Immune Regulation

ABSTRACT Excess body weight has become a global epidemic and a significant risk factor for developing chronic diseases, which are the leading causes of worldwide morbidities. Adipose tissue (AT), primarily composed of adipocytes, stores substantial amounts of energy and plays a crucial role in maintaining whole-body glucose and lipid metabolism. This helps prevent excessive body fat accumulation and lipotoxicity in peripheral tissues. In addition, AT contains endothelial cells and a substantial population of immune cells (constituting 60-70% of non-adipocyte cells), including macrophages, T and B lymphocytes, and natural killer cells. These resident immune cells engage in crosstalk with adipocytes, contributing to the maintenance of metabolic and immune homeostasis in AT. An exacerbated inflammatory response or inadequate immune resolution can lead to chronic systemic low-grade inflammation, triggering the development of metabolic alterations and the onset of chronic diseases. This review aims to elucidate the regulatory mechanisms through which immune cells influence AT function and energy homeostasis. We also focus on the interactions and functional dynamics of immune cell populations, highlighting their role in maintaining the delicate balance between metabolic health and obesity-related inflammation. Finally, understanding immunometabolism is crucial for unraveling the pathogenesis of metabolic diseases and developing targeted immunotherapeutic strategies. These strategies may offer innovative avenues in the rapidly evolving field of immunometabolism. (Rev Invest Clin. 2024;76(2):65-79)

Score for the Risk and Overall Survival of Lung Metastasis in Patients First Diagnosed With Soft Tissue Sarcoma: A Novel Nomogram-Based Risk Assessment System.

Background: Metastatic soft tissue sarcoma (STS) patients have a poor prognosis with a 3-year survival rate of 25%. About 30% of them present lung metastases (LM). This study aimed to construct 2 nomograms to predict the risk of LM and overall survival of STS patients with LM. Materials and Methods: The data of patients were derived from the Surveillance, Epidemiology, and End Results database during the period of 2010 to 2015. Logistic and Cox analysis was performed to determine the independent risk factors and prognostic factors of STS patients with LM, respectively. Afterward, 2 nomograms were, respectively, established based on these factors. The performance of the developed nomogram was evaluated with receiver operating characteristic curves, area under the curve (AUC) calibration curves, and decision curve analysis (DCA). Results: A total of 7643 patients with STS were included in this study. The independent predictors of LM in first-diagnosed STS patients were N stage, grade, histologic type, and tumor size. The independent prognostic factors for STS patients with LM were age, N stage, surgery, and chemotherapy. The AUCs of the diagnostic nomogram were 0.806 in the training set and 0.799 in the testing set. For the prognostic nomogram, the time-dependent AUC values of the training and testing set suggested a favorable performance and discrimination of the nomogram. The 1-, 2-, and 3-year AUC values were 0.698, 0.718, and 0.715 in the training set, and 0.669, 0.612, and 0717 in the testing set, respectively. Furthermore, for the 2 nomograms, calibration curves indicated satisfactory agreement between prediction and actual survival, and DCA indicated its clinical usefulness. Conclusion: In this study, grade, histology, N stage, and tumor size were identified as independent risk factors of LM in STS patients, age, chemotherapy surgery, and N stage were identified as independent prognostic factors of STS patients with LM, these developed nomograms may be an effective tool for accurately predicting the risk and prognosis of newly diagnosed patients with LM.

Human articular cartilage mechanosensitivity is related to histological degeneration - a functional MRI study.

OBJECTIVE: To investigate changes in response to sequential pressure-controlled loading and unloading in human articular cartilage of variable histological degeneration using serial T1ρ mapping. METHOD: We obtained 42 cartilage samples of variable degeneration from the medial femoral condyles of 42 patients undergoing total knee replacement. Samples were placed in a standardized artificial knee joint within an MRI-compatible whole knee-joint compressive loading device and imaged before (δ0), during (δld1, δld2, δld3, δld4, δld5) and after (δrl1, δrl2, δrl3, δrl4, δrl5) pressure-controlled loading to 0.663 ± 0.021 kN (94% body weight) using serial T1ρ mapping (spin-lock multigradient echo sequence; 3.0T MRI system [Achieva, Philips]). Reference assessment included histology (Mankin scoring) and conventional biomechanics (Tangent stiffness). We dichotomized sample into intact (n = 21) and degenerative (n = 21) based on histology and analyzed data using Mann Whitney, Kruskal Wallis, one-way ANOVA tests and Spearman's correlation, respectively. RESULTS: At δ0, we found no significant differences between intact and degenerative samples, while the response-to-loading patterns were distinctly different. In intact samples, T1ρ increases were consistent and non-significant, while in degenerative samples, T1ρ increases were significantly higher (P = 0.004, δ0 vs δld1, δ0 vs δld3), yet undulating and variable. With unloading, T1ρ increases subsided, yet were persistently elevated beyond δ0. CONCLUSION: Cartilage mechanosensitivity is related to histological degeneration and assessable by serial T1ρ mapping. Unloaded, T1ρ characteristics are not significantly different in intact vs degenerative cartilage, while load bearing is organized in intact cartilage and disorganized in degenerative cartilage.

Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs.

Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell-cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future.