Adenylate cyclase 10 promotes brown adipose tissue thermogenesis.

Brown adipose tissue (BAT) thermogenesis dissipates energy through heat production and thereby it opposes metabolic disease. It is mediated by mitochondrial membrane uncoupling, yet the mechanisms sustaining the mitochondrial membrane potential (ΔΨm) in brown adipocytes are poorly understood. Here we show that isocitrate dehydrogenase (IDH) activity and the expression of the soluble adenylate cyclase 10 (ADCY10), a CO/bicarbonate sensor residing in mitochondria, are upregulated in BAT of cold-exposed mice.

Succinate mediates inflammation-induced adrenocortical dysfunction.

The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice.

Mitochondrial-cell cycle cross-talk drives endoreplication in heart disease.

Endoreplication, duplication of the nuclear genome without cell division, occurs in disease to drive morphologic growth, cell fate, and function. Despite its criticality, the metabolic underpinnings of disease-induced endoreplication and its link to morphologic growth are unknown. Heart disease is characterized by endoreplication preceding cardiac hypertrophy.

Glycolysis is integral to histamine-induced endothelial hyperpermeability.

Histamine-induced vascular leakage is a core process of allergic pathologies, including anaphylaxis. Here, we show that glycolysis is integral to histamine-induced endothelial barrier disruption and hyperpermeability. Histamine rapidly enhanced glycolysis in endothelial cells via a pathway that involved histamine receptor 1 and phospholipase C beta signaling.

Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity.

Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with β-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth.

Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease.

Background: Enhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive.

Methods: We performed chromatin immunoprecipitation-coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence.

LC/ESI-MS/MS profiling of Ulmus parvifolia extracts and evaluation of its anti-inflammatory, cytotoxic, and antioxidant activities.

In this study, a comparative liquid chromatography/mass spectroscopy (LC/ESI-MS/MS) profiling of different fractions of Ulmus parvifolia leaves and stems was performed. Identification of compounds was based on comparing the mass spectrometric information obtained including m/z values and individual compound fragmentation pattern to tandem mass spectral library search and literature data. Eleven compounds were tentatively identified in the different analyzed fractions.