Seasonal Diet Composition of Goitered Gazelle (Gazella subgutturosa) in an Arid and Semi-Arid Region of Western China.

Global climate change, habitat fragmentation, and human interference have resulted in a significant, ongoing decline in the population of goitered gazelles. Effective conservation strategies require an understanding of resource requirements of threatened species, such as dietary needs. Therefore, we aimed to elucidate the food composition and seasonal dietary changes of goitered gazelles through microhistological analyses of fresh feces. Fabaceae (11.5%), Gramineae (9.4%), Chenopodiaceae (20.2%), Asteraceae (10.1%), and Rosaceae (19.5%) formed the primary dietary components of goitered gazelle. Additionally, Krascheninnikovia arborescens (13.4%) and Prunus sibirica (16.3%) were identified as the key forage plants. Forbs (50.4%) were the predominant plants for grazing throughout the year, particularly in the spring (72.9%). The proportion of trees in the diet was highest in the autumn (36.7%) and comparatively lower in other seasons. Furthermore, the proportions of shrubs (22.0%) and graminoids (14.8%) both reached their peaks in the winter. Our findings indicate that goitered gazelles strategically forage seasonally to cope with resource bottlenecks, enhancing their adaptability to arid and semi-arid habitats. Our study provides essential ecological information for the conservation of goitered gazelles and emphasizes the importance of dietary studies of species of ecological significance in environmentally sensitive areas.

Salvianolic acid A diminishes LDHA-driven aerobic glycolysis to restrain myofibroblasts activation and cardiac fibrosis via blocking Akt/GSK-3ß/HIF-1α axis.

Myofibroblasts activation intensively contributes to cardiac fibrosis with undefined mechanism. Salvianolic acid A (SAA) is a phenolic component derived from Salvia miltiorrhiza with antifibrotic potency. This study aimed to interrogate the inhibitory effects and underlying mechanism of SAA on myofibroblasts activation and cardiac fibrosis. Antifibrotic effects of SAA were evaluated in mouse myocardial infarction (MI) model and in vitro myofibroblasts activation model. Metabolic regulatory effects and mechanism of SAA were determined using bioenergetic analysis and cross-validated by multiple metabolic inhibitors and siRNA or plasmid targeting Ldha. Finally, Akt/GSK-3ß-related upstream regulatory mechanisms were investigated by immunoblot, q-PCR, and cross-validated by specific inhibitors. SAA inhibited cardiac fibroblasts-to-myofibroblasts transition, suppressed collage matrix proteins expression, and effectively attenuated MI-induced collagen deposition and cardiac fibrosis. SAA attenuated myofibroblasts activation and cardiac fibrosis by inhibiting LDHA-driven abnormal aerobic glycolysis. Mechanistically, SAA inhibited Akt/GSK-3ß axis and downregulated HIF-1α expression by promoting its degradation via a noncanonical route, and therefore restrained HIF-1α-triggered Ldha gene expression. SAA is an effective component for treating cardiac fibrosis by diminishing LDHA-driven glycolysis during myofibroblasts activation. Targeting metabolism of myofibroblasts might occupy a potential therapeutic strategy for cardiac fibrosis.

Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response.

Endothelial-to-mesenchymal transition (EndoMT), the process wherein endothelial cells lose endothelial identity and adopt mesenchymal-like phenotypes, constitutes a critical contributor to cardiac fibrosis. The phenotypic plasticity of endothelial cells can be intricately shaped by alteration of metabolic pathways, but how endothelial cells adjust cellular metabolism to drive EndoMT is incompletely understood. Here, we identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) as a critical driver of EndoMT via triggering abnormal glycolysis and compromising mitochondrial respiration. Pharmacological suppression of PFKFB3 with salvianolic acid C (SAC), a phenolic compound derived from Salvia miltiorrhiza, attenuates EndoMT and fibrotic response. PFKFB3-haplodeficiency recapitulates the anti-EndoMT effect of SAC while PFKFB3-overexpression augments the magnitude of EndoMT and exacerbates cardiac fibrosis. Mechanistically, PFKFB3-driven glycolysis compromises cytoplasmic nicotinamide adenine dinucleotide phosphate (reduced form, NADPH) production via hijacking glucose flux from pentose phosphate pathway. Efflux of mitochondrial NADPH through isocitrate/α-ketoglutarate shuttle replenishes cytoplasmic NADPH pool but meanwhile impairs mitochondrial respiration by hampering mitochondrial iron-sulfur cluster biosynthesis. SAC disrupts PFKFB3 stability by accelerating its degradation and thus maintains metabolic homeostasis in endothelial cells, underlying its anti-EndoMT effects. These findings for the first time identify the critical role of PFKFB3 in triggering EndoMT by driving abnormal glycolysis in endothelial cells, and also highlight the therapeutic potential for pharmacological intervention of PFKFB3 (with SAC or other PFKFB3 inhibitors) to combat EndoMT-associated fibrotic responses via metabolic regulation.