What is the clinical evidence from this study?

Study design: Other. 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.

March 10, 2015Open 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.

Resultado clave

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.

PICO estructurado

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

Población

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

Intervención

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

Comparador

Vehicle (phosphate-buffered saline) or control temperature

Resultado

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

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

Resultado numérico

valor p: p=<0.01

Limitaciones

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

Resumen

Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe(-/-) and Ldlr(-/-) mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe(-/-) and Ldlr(-/-) mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis.

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Cite This Study

Berbée et al. (Tue,) conducted a other in 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/https://doi.org/10.1038/ncomms7356

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