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Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
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PAS kinase drives lipogenesis through SREBP-1 maturation
Xiaoying Wu1, Donna Romero2, Wojciech I Swiatek1
1Department of Biochemistry, University of Utah School of Medicine, 15 N. Medical Drive East, Salt Lake City, UT 84112-5650, USA.
Cell Reports
|July 9, 2014
Summary
The study identifies PASK as a key regulator of SREBP-1c maturation, crucial for fatty acid synthesis in metabolic syndrome. Inhibiting PASK improves lipid and glucose metabolism, offering therapeutic potential.
Area of Science:
- Biochemistry
- Metabolic Diseases
- Molecular Biology
Background:
- Hyperactivation of sterol regulatory element-binding protein 1c (SREBP-1c) drives hepatic lipid synthesis, a core feature of metabolic syndrome.
- SREBP-1c activation depends on proteolytic maturation of its precursor, stimulated by feeding and insulin.
Purpose of the Study:
- To investigate the role of PASK (Pro-rich Akt substrate) in SREBP-1c maturation and its impact on metabolic syndrome.
- To evaluate PASK inhibition as a therapeutic strategy for metabolic dysfunction.
Main Methods:
- Utilized genetic and pharmacological approaches in cultured cells and animal models (mouse, rat).
- Assessed hepatic gene expression, serum lipid levels, and insulin resistance markers.
Main Results:
- Feeding and insulin stimulate hepatic PASK expression.
- PASK is essential for SREBP-1c proteolytic maturation in liver cells.
- PASK inhibition reduced lipogenic gene expression, lowered serum triglycerides, and improved insulin sensitivity in animal models.
Conclusions:
- PASK is a critical mediator in the insulin- and feeding-stimulated pathway controlling SREBP-1c activation.
- Targeting PASK demonstrates therapeutic potential for treating metabolic syndrome, obesity, and dyslipidemia.
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