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Your search keyword '"Sune Kobberup"' showing total 2 results
Start Over Author "Sune Kobberup" Publisher american society for clinical investigation
2 results on '"Sune Kobberup"'

1. Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression

Author

Weiping Zou, Jiandie D. Lin, Sune Kobberup, Zhimin Chen, Peng Zhang, Houjun Xia, Liang Guo, Siming Li, and Yanqiao Zhang

Subjects
0301 basic medicine, Programmed cell death, Adipose tissue, Inflammation, digestive system, Mice, 03 medical and health sciences, Fibrosis, Non-alcoholic Fatty Liver Disease, medicine, Animals, Humans, education, Neuregulins, Liver injury, Neuregulin-4, education.field_of_study, Cell Death, business.industry, nutritional and metabolic diseases, General Medicine, medicine.disease, digestive system diseases, Disease Models, Animal, 030104 developmental biology, Adipose Tissue, Liver, Hepatocytes, Cancer research, Disease Progression, Signal transduction, Steatosis, medicine.symptom, business, Signal Transduction, Research Article
Abstract

Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury.

Published
2017

2. Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression.

Author

Peng Zhang, Zhimin Chen, Siming Li, Lin, Jiandie D., Liang Guo, Houjun Xia, Weiping Zou, Yanqiao Zhang, Sune Kobberup, Guo, Liang, Zhang, Peng, Chen, Zhimin, Xia, Houjun, Li, Siming, Zhang, Yanqiao, Kobberup, Sune, and Zou, Weiping

Subjects
*NEUREGULINS, *FATTY liver, *ENDOCRINE genetics, *LIVER cells, *FATTY degeneration, *CELLULAR signal transduction, *GENE expression, *GENETICS, *PHYSIOLOGY, *ADIPOSE tissues, *ANIMAL experimentation, *BIOLOGICAL models, *CELL death, *COMPARATIVE studies, *EPITHELIAL cells, *GROWTH factors, *LIVER, *RESEARCH methodology, *MEDICAL cooperation, *MICE, *RESEARCH, *EVALUATION research
Abstract

Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury. [ABSTRACT FROM AUTHOR]

Published
2017
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