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Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size
Serena M Pratt1, Sally Chiu, Glenda M Espinal
1Section of Neurobiology, Physiology, Behavior, Department of Pediatrics, University of California, Davis, CA, USA.
Journal of Lipid Research
|December 8, 2009
Summary
Naturally occurring variants of hepatic lipase (HL) significantly impact lipid metabolism and lipoprotein particle size in mice. These genetic differences, despite not altering HL activity, reveal crucial insights into lipid regulation.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Research
Background:
- Hepatic lipase (HL) plays a key role in lipid metabolism.
- Naturally occurring genetic variants can influence protein function and physiological outcomes.
- Understanding HL variants is crucial for clarifying its role in lipid homeostasis.
Purpose of the Study:
- To investigate the in vivo effects of naturally occurring hepatic lipase (HL) coding sequence variants.
- To determine if specific amino acid differences in HL influence lipid and lipoprotein metabolism.
- To assess allele and sex-specific effects on plasma lipids and lipoprotein particle size.
Main Methods:
- Generation of transgenic mice expressing SPRET/EiJ-HL (SPRET-HL) and comparison with C57BL/6J-HL (B6) controls.
- Measurement of HL mRNA and activity in transgenic mice.
- Analysis of plasma lipid levels (total cholesterol, triglycerides) and lipoprotein particle size in fed and fasted male and female mice.
Main Results:
- SPRET-HL transgenics showed significant allelic effects on plasma lipids, with reductions in total cholesterol and triglycerides observed in males and females.
- SPRET-HL mediated reductions in VLDL-, LDL-, and HDL-cholesterol in fed males.
- Allele and sex influenced lipoprotein particle size, with altered VLDL, LDL, and HDL sizes noted in transgenic males and females.
Conclusions:
- Naturally occurring HL coding sequence variants exert divergent effects on lipid and lipoprotein metabolism.
- Genetic variations in HL, independent of overall activity levels, significantly modulate plasma lipid profiles.
- These findings highlight the importance of specific HL alleles in regulating lipoprotein metabolism and underscore sex-specific responses.
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