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09:41
Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
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GR-KLF15 pathway controls hepatic lipogenesis during fasting.
Yoshinori Takeuchi1,2,3, Yuki Murayama1,2, Yuichi Aita1,2
1Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
The FEBS Journal
|September 13, 2023
Summary
During fasting, the glucocorticoid receptor (GR) regulates liver fat production by controlling Kruppel-like factor 15 (KLF15) and sterol regulatory element-binding protein-1 (SREBP-1) expression. This pathway is crucial for metabolic adaptation to fasting.
Area of Science:
- Metabolic regulation
- Molecular biology
- Endocrinology
Background:
- Fasting induces a metabolic shift, suppressing lipogenesis and activating gluconeogenesis.
- Sterol regulatory element-binding protein-1 (SREBP-1) is key in lipogenesis regulation and suppressed during fasting.
- Kruppel-like factor 15 (KLF15) interacts with the liver X receptor to regulate SREBP-1, but its fasting induction mechanism is unknown.
Purpose of the Study:
- To elucidate the mechanism of KLF15 induction during fasting.
- To investigate the role of the glucocorticoid receptor (GR) in regulating hepatic KLF15 expression and lipogenesis during fasting.
- To understand the interplay between the HPA axis, GR, KLF15, and SREBP-1 in fasting-induced metabolic adaptation.
Main Methods:
- Utilized KLF15 knockout mice to assess KLF15 necessity in GR-mediated SREBP-1 suppression.
- Examined GR binding to the KLF15 enhancer during fasting.
- Investigated the GR-KLF15-SREBP-1 pathway's role in hepatic lipogenesis during fasting.
Main Results:
- Glucocorticoid receptor (GR) directly regulates hepatic KLF15 expression during fasting.
- KLF15 is essential for GR-mediated suppression of SREBP-1 and subsequent reduction in hepatic lipogenesis.
- GR exhibits enhanced binding to the KLF15 enhancer in response to fasting, indicating its involvement in the fasting response.
Conclusions:
- The HPA axis-regulated GR-KLF15 pathway is a critical mechanism controlling hepatic lipogenesis during fasting.
- This pathway highlights the intricate molecular regulation of lipid metabolism in response to nutritional status.
- Findings provide insights into the hormonal control of metabolic adaptation during fasting.
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