A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice.

Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages' engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.

Pre-stroke Physical Inactivity and Stroke Severity in Male and Female Patients.

Introduction: Females experience more severe ischemic strokes than do males. A higher pre-stroke physical activity level is associated with less severe stroke. The primary aim of this study was to explore the association between pre-stroke physical inactivity and stroke severity in male and female patients. Methods: This was a retrospective, registry-based study. The data were retrieved from two stroke registries from 2014 to 2019. The primary explanatory variable was physical activity level before the stroke, assessed using the Saltin-Grimby Physical Activity Level Scale. The outcome was moderate to severe stroke at hospital admission, assessed using the National Institutes of Health Stroke Scale (NIHSS). A moderate to severe stroke was defined as a NIHSS score of ≥6. Binary logistic regression analysis was performed to explore if physical inactivity before the stroke could explain stroke severity in male and female patients. Results: In total, we included 4,535 patients with ischemic stroke. Female patients (n = 2,145) had a mean age of 76 years, 35% had a moderate to severe stroke, and 64% were physically inactive pre-stroke. Male patients (n = 2,390) had a mean age of 72 years, 25% had a moderate to severe stroke, and 49% were physically inactive pre-stroke. Physical inactivity was associated with higher odds for moderate to severe stroke in both sexes (females' odds ratio [OR], 2.7, 95% confidence interval [CI]: 2.2-3.3, p < 0.001 and males' OR, 2.06, 95% CI: 1.7-2.5, p < 0.001). The association remained significant in the adjusted models. Conclusions: Physically inactive females and males had higher odds of experiencing a moderate to severe stroke. However, the OR of female patients was somewhat higher than that of male patients.