Endothelial Prohibitin Mediates Bidirectional Long-Chain Fatty Acid Transport in White and Brown Adipose Tissues

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The function of prohibitin-1 (PHB1) in adipocyte mitochondrial respiration, adaptive thermogenesis, and long-chain fatty acid (LCFA) metabolism has been reported. While intracellular PHB1 expression is ubiquitous, cell surface PHB1 localization is selective for adipocytes and endothelial cells of adipose tissue. The importance of PHB1 in adipose endothelium has not been investigated, and its vascular cell surface function has remained unclear. Here, we generated and analyzed mice with PHB1 knock-out specifically in endothelial cells (PHB1 EC-KO). Despite the lack of endothelial PHB1, mice developed normally and had normal vascularization in both white adipose tissue and brown adipose tissue (BAT). Tumor and ex vivo explant angiogenesis assays also have not detected a functional defect in PHB1 KO endothelium. No metabolic phenotype was observed in PHB1 EC-KO mice raised on a regular diet. We show that both male and female PHB1 EC-KO mice have normal body composition and adaptive thermogenesis. However, PHB1 EC-KO mice displayed higher insulin sensitivity and increased glucose clearance when fed a high-fat diet. We demonstrate that the efficacy of LCFA deposition by adipocytes is decreased by PHB1 EC-KO, in particular in BAT. Consistent with that, EC-KO mice have a defect in clearing triglycerides from systemic circulation. Free fatty acid release upon lipolysis induction was als

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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