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Updated: Aug 11, 2026
Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Angptl3-null mice show low plasma lipid concentrations by enhanced lipoprotein lipase activity
Kazunori Fujimoto1, Ryuta Koishi, Tetsuya Shimizugawa
1Medicinal Safety Research Laboratories, Sankyo Co., Ltd., Fukuroi, Shizuoka, Japan.
Abstract:
Angiopoietin-like 3 (ANGPTL3) is a secreted protein with both angiogenesis and lipid metabolism functions. We generated knockout mice that failed to express the Angptl3 gene, and analyzed the lipid metabolism. Angptl3-null mice, fed a normal diet or a high-fat, high-calorie (HFC) diet, revealed markedly low plasma lipid concentrations, especially plasma triglyceride concentration, although the body weight and liver weight were not different between Angptl3-null mice and wild-type mice. Angptl3-null mice fed an HFC diet also revealed a significantly reduced epididymal adipose tissue weight despite there being no difference in adipocyte size between them and wild-type mice. A triglyceride clearance study indicated that the lower plasma triglyceride concentration in Angptl3-null mice was caused by an accelerated clearance of triglyceride. In fact, lipoprotein lipase and hepatic lipase activities in the post-heparin plasma of Angptl3-null mice were 1.57 times and 1.42 times higher than those of wild-type mice, respectively. These results suggest that ANGPTL3 may have an effect not only on lipid metabolism but also on adipose formation.
Insights
Mice lacking Angiopoietin-like 3 (ANGPTL3) showed significantly lower blood triglyceride levels and reduced fat tissue. This was due to faster triglyceride clearance, indicating ANGPTL3 influences lipid metabolism and fat formation.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Research
Background:
- Angiopoietin-like 3 (ANGPTL3) is a protein involved in angiogenesis and lipid metabolism.
- Understanding ANGPTL3's role is crucial for metabolic disease research.
Purpose of the Study:
- To investigate the function of ANGPTL3 in lipid metabolism using a knockout mouse model.
- To analyze the impact of ANGPTL3 deficiency on plasma lipids and adipose tissue.
Main Methods:
- Generation of Angptl3-null mice.
- Analysis of plasma lipid concentrations under normal and high-fat diets.
- Measurement of epididymal adipose tissue weight and adipocyte size.
- Triglyceride clearance studies and lipase activity assays.
Main Results:
- Angptl3-null mice exhibited markedly low plasma triglyceride concentrations.
- Reduced epididymal adipose tissue weight was observed in Angptl3-null mice on a high-fat diet.
- Triglyceride clearance was accelerated in Angptl3-null mice, with increased lipoprotein lipase and hepatic lipase activities.
Conclusions:
- ANGPTL3 plays a significant role in regulating lipid metabolism and triglyceride levels.
- ANGPTL3 deficiency leads to enhanced triglyceride clearance and impacts adipose tissue formation.
- These findings suggest ANGPTL3 as a potential therapeutic target for metabolic disorders.
