Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Mol Metab. 2023 Apr;70:101693. doi: 10.1016/j.molmet.2023.101693. Epub 2023 Feb 14.
Genome-wide association studies (GWAS) have identified genetic variants in SEC16 homolog B (SEC16B) locus to be associated with obesity and body mass index (BMI) in various populations. SEC16B encodes a scaffold protein located at endoplasmic reticulum (ER) exit sites that is implicated to participate in the trafficking of COPII vesicles in mammalian cells. However, the function of SEC16B in vivo, especially in lipid metabolism, has not been investigated.
We generated Sec16b intestinal knockout (IKO) mice and assessed the impact of its deficiency on high-fat diet (HFD) induced obesity and lipid absorption in both male and female mice. We examined lipid absorption in vivo by acute oil challenge and fasting/HFD refeeding. Biochemical analyses and imaging studies were performed to understand the underlying mechanisms.
Our results showed that Sec16b intestinal knockout (IKO) mice, especially female mice, were protected from HFD-induced obesity. Loss of Sec16b in intestine dramatically reduced postprandial serum triglyceride output upon intragastric lipid load or during overnight fasting and HFD refeeding. Further studies showed that intestinal Sec16b deficiency impaired apoB lipidation and chylomicron secretion.
Our studies demonstrated that intestinal SEC16B is required for dietary lipid absorption in mice. These results revealed that SEC16B plays important roles in chylomicron metabolism, which may shed light on the association between variants in SEC16B and obesity in human.
全基因组关联研究（GWAS）已经确定 SEC16 同源物 B（SEC16B）基因座中的遗传变异与各种人群中的肥胖和体重指数（BMI）相关。SEC16B 编码一种位于内质网（ER）出口位点的支架蛋白，该蛋白被认为参与了哺乳动物细胞中 COPII 囊泡的运输。然而，SEC16B 在体内的功能，特别是在脂质代谢中的功能，尚未得到研究。
我们生成了 Sec16b 肠道敲除（IKO）小鼠，并评估了其缺失对雄性和雌性小鼠高脂肪饮食（HFD）诱导的肥胖和脂质吸收的影响。我们通过急性油挑战和禁食/HFD 再喂养来研究体内的脂质吸收。进行了生化分析和成像研究以了解潜在的机制。
我们的结果表明，Sec16b 肠道敲除（IKO）小鼠，特别是雌性小鼠，对 HFD 诱导的肥胖具有保护作用。肠道 Sec16b 的缺失显著降低了胃内脂质负荷或夜间禁食和 HFD 再喂养期间餐后血清甘油三酯的输出。进一步的研究表明，肠道 Sec16b 缺乏会损害 apoB 脂质化和乳糜微粒分泌。
我们的研究表明，肠道 SEC16B 是小鼠膳食脂质吸收所必需的。这些结果表明 SEC16B 在乳糜微粒代谢中发挥重要作用，这可能为 SEC16B 变异与人类肥胖之间的关联提供了启示。
