棕色脂肪组织(BAT)已成为心脏代谢疾病的吸引人的治疗靶标。BAT是产热器官并且在激活时显著降低高脂血症。为了应对寒冷的暴露,不仅增加了脂质对BAT的摄取,而且触发了Cyp7b1介导的从肝脏中胆固醇合成胆汁酸(BA)。除了它们对肠道脂质消化的作用外,BA作为内分泌信号,可以激活BAT中的产热。当暴露在寒冷的温度下,Cyp7b1-/-小鼠的BAT功能受损,粪便胆汁酸水平降低。这里,我们旨在评估Cyp7b1在BAT依赖性脂质清除中的作用。使用放射性示踪剂的代谢研究,我们表明,作为对冷刺激的反应,BAT介导的来自富含甘油三酯的脂蛋白(TRL)的脂肪酸的清除,它们的残留物在Cyp7b1-/-小鼠中减少。脂质摄取受损可以通过Cyp7b1-/-小鼠中BAT脂蛋白脂肪酶(LPL)水平降低和器官活性受损来解释,这可能与受损的胰岛素信号有关。总的来说,我们的发现表明,由冷激活的BAT介导的全身脂蛋白代谢的改变是依赖性的,至少在某种程度上,在CYP7Β1上。
Brown adipose tissue (BAT) has emerged as an appealing therapeutic target for cardio metabolic diseases. BAT is a heat-producing organ and upon activation substantially lowers hyperlipidemia. In response to cold exposure, not only the uptake of lipids into BAT is increased but also the
Cyp7b1-mediated synthesis of bile acids (BA) from cholesterol in the liver is triggered. In addition to their role for intestinal lipid digestion, BA act as endocrine signals that can activate thermogenesis in BAT. When exposed to cold temperatures,
Cyp7b1 -/- mice have compromised BAT function along with reduced fecal bile acid levels. Here, we aim to evaluate the role of
Cyp7b1 for BAT-dependent lipid clearance. Using metabolic studies with radioactive tracers, we show that in response to a cold stimulus, BAT-mediated clearance of fatty acids derived from triglyceride-rich lipoproteins (TRL), and their remnants are reduced in
Cyp7b1 -/- mice. The impaired lipid uptake can be explained by reduced BAT lipoprotein lipase (LPL) levels and compromised organ activity in
Cyp7b1 -/- mice, which may be linked to impaired insulin signaling. Overall, our findings reveal that alterations of systemic lipoprotein metabolism mediated by cold-activated BAT are dependent, at least in part, on CYP7Β1.