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Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
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ANGPTL8 has both endocrine and autocrine effects on substrate utilization
Federico Oldoni1, Haili Cheng1, Serena Banfi1
1Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
JCI Insight
|July 31, 2020
Summary
Angiopoietin-like protein 8 (ANGPTL8) from the liver directs dietary fats to storage, while ANGPTL8 from fat tissue promotes fat breakdown. This dual action ensures energy availability after meals.
Area of Science:
- Metabolism
- Endocrinology
- Lipid Biology
Background:
- Angiopoietin-like protein 8 (ANGPTL8) is crucial for regulating triglyceride (TG) delivery by inhibiting lipoprotein lipase (LPL).
- ANGPTL8 is expressed in liver and adipose tissue, playing a role in redirecting dietary TG after food intake.
Purpose of the Study:
- To investigate the distinct roles of hepatic and adipose ANGPTL8 in regulating TG metabolism.
- To elucidate the mechanisms by which ANGPTL8 influences LPL activity and lipid distribution.
Main Methods:
- Utilized mouse models lacking hepatic or adipose ANGPTL8.
- Assessed plasma TG levels, intravascular LPL activity, and lipid delivery to tissues.
- Investigated ANGPTL8 interactions with ANGPTL4 in cultured cells.
Main Results:
- Hepatic ANGPTL8 deficiency led to low plasma TG and reduced lipid delivery to adipose tissue.
- Adipose ANGPTL8 deficiency resulted in elevated postprandial TG levels.
- ANGPTL8, with ANGPTL4, reduced ANGPTL4 secretion and ANGPTL4-mediated LPL inhibition in vitro.
Conclusions:
- Hepatic ANGPTL8 acts endocrinely to inhibit LPL in oxidative tissues, facilitating TG storage.
- Adipose ANGPTL8 acts in an autocrine/paracrine manner to enhance LPL activity by inhibiting ANGPTL4.
- These differential actions of ANGPTL8 optimize TG replenishment and energy availability.
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