What is the clinical evidence from this study?

Population: Hypercholesterolaemia and atherosclerosis. Intervention: CL316243 vs. Vehicle (PBS). Primary outcome: Mean atherosclerotic lesion area (p=<0.01).

What does this research mean for the field?

Activation of brown adipose tissue by the beta3-adrenergic receptor agonist CL316243 reduces mean atherosclerotic lesion area by 43% in hyperlipidemic APOE*3-Leiden.CETP mice. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the role of brown adipose tissue activation in plasma cholesterol metabolism and atherosclerosis development.

March 10, 2015Nature CommunicationsOpen Access

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

Q: What are the key findings of this study?

Activation of brown adipose tissue by the beta3-adrenergic receptor agonist CL316243 reduced mean atherosclerotic lesion area by 43% compared to vehicle in hyperlipidemic APOE*3-Leiden.CETP mice.

Q: What does this research mean for the field?

Activation of brown adipose tissue by the beta3-adrenergic receptor agonist CL316243 reduces mean atherosclerotic lesion area by 43% in hyperlipidemic APOE*3-Leiden.CETP mice. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine the role of brown adipose tissue activation in plasma cholesterol metabolism and atherosclerosis development.

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Key result

Activation of brown adipose tissue by the beta3-adrenergic receptor agonist CL316243 reduced mean atherosclerotic lesion area by 43% compared to vehicle in hyperlipidemic APOE*3-Leiden.CETP mice.

Why the study?

Does selective β3-adrenergic receptor agonist CL316243 reduce plasma cholesterol and atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice?

Population

Female hyperlipidemic APOE*3-Leiden.CETP mice, Apoe-/- mice, and Ldlr-/- mice fed an atherogenic…

Comparison

Selective β3-adrenergic receptor agonist… vs Vehicle or control temperature

Design

Preclinical

Follow-up

10 weeks

Authors

JBJimmy F.P. BerbéeLeiden University Medical Center MBMariëtte R. BoonLeiden University Medical Center PKPadmini P. S. J. KhedoeLeiden University Medical Center

Discussion

Member takes

Implication

BAT activation merits human trials of β3-agonists; leaves open translation to clinical atherosclerosis prevention.

Key Points

To determine the role of brown adipose tissue activation in plasma cholesterol metabolism and atherosclerosis development.
Stimulated β3-adrenergic receptors to activate brown adipose tissue in hyperlipidemic APOE*3-Leiden.CETP mice displaying human-like lipoprotein metabolism.
Assessed energy expenditure, plasma triglyceride levels, and remnant clearance in APOE*3-Leiden.CETP mice alongside Apoe-deficient and Ldlr-deficient mouse models.
Brown adipose tissue activation increased energy expenditure and decreased plasma triglyceride and cholesterol levels.
Activation accelerated the selective uptake of fatty acids from triglyceride-rich lipoproteins into brown fat, driving rapid hepatic clearance of cholesterol-enriched remnants.
Apoe(-/-) and Ldlr(-/-) mice exhibited no reduction in hypercholesterolaemia or atherosclerosis, confirming that vascular protection requires a functional hepatic apoE-LDLR clearance pathway.

Structured PICO

Does selective β3-adrenergic receptor agonist CL316243 reduce plasma cholesterol and atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice?

Population

Female hyperlipidemic APOE*3-Leiden.CETP mice, Apoe-/- mice, and Ldlr-/- mice fed an atherogenic Western-type diet (WTD)

Intervention

Selective β3-adrenergic receptor agonist CL316243 (3 x 20 mg per mouse per week; subcutaneous) for up to 10 weeks, or cold exposure for 7 days

Comparator

Vehicle (phosphate-buffered saline) or control temperature

Outcome

Plasma triglyceride levels, plasma cholesterol levels, and atherosclerotic lesion areasurrogate

Main Result

p-value: p=<0.01

Activation of brown adipose tissue lowers atherogenic lipoproteins and protects against atherosclerosis via an apoE-LDLR-dependent clearance pathway.

Limitations

Animal model results may not fully translate to humans
The anti-atherogenic effect depends on a functional hepatic apoE-LDLR clearance pathway, rendering Apoe-/- and Ldlr-/- mice inappropriate models for this specific mechanism

Cite This Study

Berbée et al. (2015) studied Hypercholesterolaemia and atherosclerosis. CL316243 vs. Vehicle (PBS) was evaluated on Mean atherosclerotic lesion area (p=<0.01). Activation of brown adipose tissue by the beta3-adrenergic receptor agonist CL316243 reduced mean atherosclerotic lesion area by 43% compared to vehicle in hyperlipidemic APOE*3-Leiden.CETP mice.

synapsesocial.com/papers/6a176da7cf49e78c48b4099f https://doi.org/10.1038/ncomms7356

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Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider