What does this research mean for the field?

Angptl3 and Angptl4 regulate circulating triglyceride levels during different nutritional states (feeding versus fasting) through differential inhibition of lipoprotein lipase. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine how Angptl3 and Angptl4 regulate lipoprotein lipase activity and triglyceride clearance during fed and fasted nutritional states.

August 5, 2005EndocrinologyOpen Access

Transgenic Angiopoietin-Like (Angptl)4 Overexpression and Targeted Disruption of Angptl4 and Angptl3: Regulation of Triglyceride Metabolism

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Population

Mice

Comparison

Targeted genetic disruption of Angptl4 and/or… vs Control/wild-type mice (implied)

Design

Preclinical

Authors

AKAnja KösterUniversity of Tartu YCYe ChaoEli Lilly (United States)MMMarian MosiorEli Lilly (United States)

Discussion

Member takes

Implication

Preclinical Angptl3/4-LPL data require human validation; leaves open therapeutic translation in dyslipidemia.

Key Points

To determine how Angptl3 and Angptl4 regulate lipoprotein lipase activity and triglyceride clearance during fed and fasted nutritional states.
Generated Angptl3-deficient, Angptl4-deficient, double-deficient, and liver-specific human Angptl4-overexpressing transgenic mouse models.
Evaluated mouse and recombinant human lipoprotein lipase (LPL) inhibition in vitro using purified recombinant Angptl4 protein.
Measured circulating triglyceride concentrations and postheparin plasma LPL activity across fed and fasted conditions.
Transgenic overexpression of human Angptl4 in mice increased plasma triglycerides and reduced postheparin plasma LPL activity, consistent with direct in vitro LPL inhibition by recombinant Angptl4.
Angptl4 deficiency caused hypotriglyceridemia and increased postheparin plasma LPL activity predominantly during fasting, whereas Angptl3 deficiency produced stronger effects in the fed state.
Combined deficiency of Angptl3 and Angptl4 exerted an additive lowering effect on plasma triglycerides and resulted in lethality before two months of age.

Structured PICO

Population

Mice (Angptl4-deficient, Angptl3-deficient, double-deficient, and transgenic mice overexpressing human Angptl4 in the liver)

Intervention

Targeted genetic disruption of Angptl4 and/or Angptl3, or transgenic overexpression of human Angptl4

Comparator

Control/wild-type mice (implied)

Outcome

Plasma triglyceride levels and postheparin plasma (PHP) lipoprotein lipase (LPL) activitysurrogate

Angptl3 and Angptl4 differentially regulate circulating triglyceride levels during feeding and fasting states through the inhibition of lipoprotein lipase.

Cite This Study

Köster et al. (2005) studied this question.

synapsesocial.com/papers/6a1e80657f6e8bbb23690263 https://doi.org/10.1210/en.2005-0476

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Transgenic Angiopoietin-Like (Angptl)4 Overexpression and Targeted Disruption of Angptl4 and Angptl3: Regulation of Triglyceride Metabolism

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Transgenic Angiopoietin-Like (Angptl)4 Overexpression and Targeted Disruption of Angptl4 and Angptl3: Regulation of Triglyceride Metabolism

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

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