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A high-throughput, image-based screen to identify kinases involved in brown adipocyte development
Aliki Perdikari1, Elisabeth Kulenkampff1, Carla Rudigier1
1Institute of Food, Nutrition and Health, ETH-Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
Science Signaling
|February 16, 2017
Summary
Brown adipose tissue (BAT) generates heat to combat obesity. Kinase signaling significantly impacts brown adipocyte formation, with 5' AMP-activated protein kinase (AMPK) promoting the development of heat-generating cells.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolism
Background:
- Brown adipose tissue (BAT) mediates non-shivering thermogenesis via uncoupling protein 1 (UCP1).
- BAT activation is a potential therapeutic strategy for obesity.
- Kinase signaling pathways are crucial regulators of cellular differentiation and function.
Purpose of the Study:
- To investigate the role of kinase signaling in brown adipocyte formation.
- To identify specific kinases that regulate the development of BAT.
Main Methods:
- Utilized lentiviral-mediated short hairpin RNA (shRNA) knockdown and pharmacological inhibitors.
- Employed a high-content, high-throughput in vitro image-based screening approach.
- Assessed effects on brown adipocyte proliferation, differentiation, and formation.
Main Results:
- Identified 190 kinases influencing brown adipocyte development.
- Discovered that 5' AMP-activated protein kinase (AMPK) promotes brown adipocyte formation.
- Observed that AMPK-regulated brown adipocytes exhibit increased UCP1 expression.
Conclusions:
- Kinase signaling plays a significant role in regulating brown adipocyte formation.
- AMPK is a key promoter of brown adipocyte development and UCP1 abundance.
- Findings offer insights into molecular targets for modulating BAT activity.
