Background:
Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease (CVD), and recent studies have also identified BAT as an endocrine organ. While BAT has been implicated to be protective in cardiovascular disease, to this point there are no studies that identify a direct role for BAT to mediate cardiac function.
Methods:
To determine the role of BAT on cardiac function, we utilized a model of BAT transplantation. We then performed lipidomics and identified an increase in the lipokine, 12,13-diHOME. We utilized a mouse model with sustained overexpression of 12,13-diHOME and investigated the role of 12,13-diHOME in a NOS1
-/-
mouse and in isolated cardiomyocytes to determine effects on function and respiration. We also investigated 12,13-diHOME in a cohort of human patients with heart disease.
Results:
Here, we determined that transplantation of BAT (+BAT) improves cardiac function via the release of the lipokine 12,13-diHOME. Sustained overexpression of 12,13-diHOME using tissue nanotransfection negated the deleterious effects of a high-fat diet on cardiac function and remodeling, and acute injection of 12,13-diHOME increased cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13-diHOME increased mitochondrial respiration. The effects of 12,13-diHOME were absent in
NOS1
-/-
mice and cardiomyocytes. We also provide the first evidence that 12,13-diHOME is decreased in human patients with heart disease.
Conclusions:
Our results identify an endocrine role for BAT to enhance cardiac function that is mediated by regulation of calcium cycling via 12,13-diHOME and NOS1.
Lye (sodium hydroxide [NaOH]) peeling is the most common method for peeling tomatoes in the Midwest U.S. With the rise in the cost of NaOH and the associated disposal problems, alternative methods for peeling need to be examined. Solutions of NaOH, potassium hydoxide (KOH) and calcium hydroxide (Ca[OH]
2
) at different concentrations were compared to determine their efficacy as peeling agents. Ca(OH)
2
was ineffective as a peeling agent because of its low solubility. KOH produced peeling equivalent to NaOH, but at half the normality. A lower normality is needed because of the increased reactivity of KOH compared to NaOH. This is further demonstrated by the addition of salts to the solution. The use of KOH instead of NaOH may result in cost savings and decreased waste disposal problems.
Acute respiratory distress syndrome (ARDS) represents a significant burden to the healthcare system, with ≈200 000 cases diagnosed annually in the USA. ARDS patients suffer from severe refractory hypoxemia, alveolar‐capillary barrier dysfunction, impaired surfactant function, and abnormal upregulation of inflammatory pathways that lead to intensive care unit admission, prolonged hospitalization, and increased disability‐adjusted life years. Currently, there is no cure or FDA‐approved therapy for ARDS. This work describes the implementation of engineered extracellular vesicle (eEV)‐based nanocarriers for targeted nonviral delivery of anti‐inflammatory payloads to the inflamed/injured lung. The results show the ability of surfactant protein A (SPA)‐functionalized IL‐4‐ and IL‐10‐loaded eEVs to promote intrapulmonary retention and reduce inflammation, both in vitro and in vivo. Significant attenuation is observed in tissue damage, proinflammatory cytokine secretion, macrophage activation, influx of protein‐rich fluid, and neutrophil infiltration into the alveolar space as early as 6 h post‐eEVs treatment. Additionally, metabolomics analyses show that eEV treatment causes significant changes in the metabolic profile of inflamed lungs, driving the secretion of key anti‐inflammatory metabolites. Altogether, these results establish the potential of eEVs derived from dermal fibroblasts to reduce inflammation, tissue damage, and the prevalence/progression of injury during ARDS via nonviral delivery of anti‐inflammatory genes/transcripts.
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