A5088591742- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Fibroblast Growth Factor Research
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Lipid metabolism and disorders
- Hippo pathway signaling and YAP/TAZ
- Kruppel-like factors research
- Muscle Physiology and Disorders
- Muscle metabolism and nutrition
- FOXO transcription factor regulation
- Autophagy in Disease and Therapy
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Alcohol Consumption and Health Effects
University of Pennsylvania
2018-2023
Cancer Research Institute
2018
Brown adipose tissue (BAT) activity protects animals against hypothermia and represents a potential therapeutic target to combat obesity. The transcription factor early B cell factor-2 (EBF2) promotes brown adipocyte differentiation, but its roles in maintaining fate stimulating BAT recruitment during cold exposure were unknown. We find that the deletion of Ebf2 adipocytes mice ablates character function, resulting intolerance. Unexpectedly, prolonged restores thermogenic profile function...
Abstract Terminal differentiation opposes proliferation in the vast majority of tissue types. As a result, loss lineage is hallmark aggressive cancers, including soft sarcomas (STS). Consistent with these observations, undifferentiated pleomorphic sarcoma (UPS), an STS subtype devoid markers, among most lethal adults. Though tissue-specific features are lost mesenchymal tumors they commonly diagnosed skeletal muscle, and thought to develop from transformed muscle progenitor cells. We have...
Brown adipose tissue (BAT) generates heat to maintain body temperature and suppress obesity. Agonists for nuclear receptors PPARα PPARγ both affect brown adipocyte function, yet the interplay between these factors in BAT is uncertain. Here, we report that shares most genomic binding sites with PPARγ, common are more related function than PPARγ-selective without PPARα. Integrating occupancy cold-responsive transcriptomes identifies a subset of 16 genes potential relevance function. Among...
There is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated (ALD) with regards to risk factors progression. However, the mechanism by which arises from concomitant obesity overconsumption of alcohol (syndrome metabolic disease; SMAFLD), not fully understood.Male C57BL6/J mice were fed chow diet (Chow) or high-fructose, high-fat, high-cholesterol (FFC) for 4 weeks, then administered either saline ethanol (EtOH, 5% in drinking water) another 12 weeks....
Stress-induced hyperglycemia is associated with poor outcomes in nearly all critical illnesses. This acute elevation glucose after injury or illness increased morbidity and mortality, including multiple organ failure. often attributed to insulin resistance as controlling levels via exogenous improves outcomes, but the mechanisms are unclear. Forkhead box O (FOXO) transcription factors direct targets of signaling liver that regulate homeostasis indirect pathways. Loss hepatic FOXO reduces...
Organismal stressors such as cold exposure require a systemic response to maintain body temperature. Brown adipose tissue (BAT) is key thermogenic in mammals that protects against hypothermia exposure. Defining the complex interplay of multiple organ systems this fundamental our understanding thermogenesis. In study, we identify role for hepatic insulin signaling via AKT adaptive stress and show liver an essential cell-nonautonomous regulator adipocyte lipolysis BAT function....
Abstract The hepatic transcription factor forkhead box O1 (FOXO1) is a critical regulator of and systemic insulin sensitivity. Previous work by our group others demonstrated that genetic inhibition FOXO1 improves sensitivity both in dietary mouse models metabolic disease. Mechanistically, this due part to cell nonautonomous control adipose tissue However, the mechanisms mediating liver-adipose crosstalk remain ill defined. One candidate hepatokine controlled fibroblast growth 21 (FGF21)....
The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) measure nascent fasting refeeding as well define specific role in mediating this response. We identified 599 feeding-regulated transcripts, over 6,000 eRNAs, mapped their dependency on signaling. Further, several lncRNAs, including lncRNA Gm11967, whose expression was dependent upon liver Akt-FoxO1 axis. Restoring...