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A central question in physiology is how different organs communicate with each other to maintain whole-organism homeostasis. Research in the past 20 years revealed that non-glandular organs such as adipose tissue, liver and skeletal muscle can secrete hormones that regulate whole-body metabolism. In contrast, little is known regarding heart-derived hormones save for ANP gas after eating meat and BNP, each discovered over 30 years ago. We recently discovered that Growth Differentiation Factor 15 (GDF15) is a new heart-derived hormone. Circulating GDF15 acts on the liver to inhibit growth hormone signaling and body growth. Plasma GDF15 is increased in children electricity in costa rica current with concomitant heart disease and failure to thrive (FTT). Our results explain a well-established clinical observation that children with heart diseases often develop FTT. More importantly, these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Plasma GDF15 was recently shown to be elevated in patients with various heart diseases and is associated wikipedia electricity generation with increased morbidity and mortality. However, how GDF15 is increased in heart disease remains unclear. We tackled this clinically important question and identified the whole gene regulatory network that induces GDF15 transcription in heart electricity jokes riddles disease, using massively parallel single-nucleus RNA-Seq (~20,000 nuclei). This study also revealed for the first time the organ composition, cell type and heterogeneity in normal postnatal, developing mouse heart, and the profound changes of transcriptional landscape of every cell type in the disease state. In addition, we have identified the key enzymes that process gas 0095 GDF15 pro-hormone into its mature form. Together, these studies helped pioneer a new field of cardiac endocrinology.

Metabolic dysfunction directly causes or significantly contributes to many human diseases including heart disease, obesity, diabetes, cancer and aging. Most cells have limited capacity to store energy; therefore cellular gas in oil pan energy supply and demand must be coordinated. In addition, different cell types exhibit preference for specific metabolic pathways (fatty acid oxidation/FAO, glycolysis or oxidative phosphorylation/OxPhos). For instance, neurons rely on glycolysis and ensuing OxPhos but not FAO, while cardiomyocytes use OxPhos and FAO to generate most energy for cardiac contraction. However, it is little understood world j gastrointest surg impact factor how specific metabolic pathways are coordinately regulated to support cell type-specific function. Work from my lab using cell type-specific KO mice and genomic approaches (ChIP-Seq and RNA-Seq) filled this knowledge gap by identifying the transcription youtube gas station karaoke factor estrogen-related receptor gamma (ERRγ) as a key transcriptional coordinator of cellular energy supply and demand. Mechanistically we showed that ERRγ directly regulates hundreds of OxPhos genes, and cooperates with distinct transcription factors to regulate cell type-specific metabolic (FAO) and functional genes. Accordingly, ERRγ is essential for normal cardiac contraction and conduction1, neuronal function and learning/memory, and renal reabsorption. Together, these studies revealed how cellular energy production and consumption are elegantly coordinated in a cell type-specific k electric jobs 2016 manner.