Department of Biomedical Sciences, Heritage College of Osteopathic Medicine and Diabetes Institute, Ohio University, Athens, OH 45701, USA.
Department of Biological Sciences, Ohio University, Athens, OH 45701, USA.
Nutrients. 2023 May 26;15(11):2486. doi: 10.3390/nu15112486.
Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice. However, the physiological role of continuous infusion of recombinant APOA4 protein in regulating sympathetic activity, thermogenesis, and lipid and glucose metabolism in low-fat-diet (LFD)-fed mice remained elusive. The hypothesis of this study was that continuous infusion of mouse APOA4 protein would increase sympathetic activity and thermogenesis in BAT and subcutaneous inguinal white adipose tissue (IWAT), attenuate plasma lipid levels, and improve glucose tolerance. To test this hypothesis, sympathetic activity, BAT temperature, energy expenditure, body weight, fat mass, caloric intake, glucose tolerance, and levels of BAT and IWAT thermogenic and lipolytic proteins, plasma lipids, and markers of fatty acid oxidation in the liver in mice with APOA4 or saline treatment were measured. Plasma APOA4 levels were elevated, BAT temperature and thermogenesis were upregulated, and plasma triglyceride (TG) levels were reduced, while body weight, fat mass, caloric intake, energy expenditure, and plasma cholesterol and leptin levels were comparable between APOA4- and saline-treated mice. Additionally, APOA4 infusion stimulated sympathetic activity in BAT and liver but not in IWAT. APOA4-treated mice had greater fatty acid oxidation but less TG content in the liver than saline-treated mice had. Plasma insulin in APOA4-treated mice was lower than that in saline-treated mice after a glucose challenge. In conclusion, continuous infusion of mouse APOA4 protein stimulated sympathetic activity in BAT and the liver, elevated BAT thermogenesis and hepatic fatty acid oxidation, and consequently attenuated levels of plasma and hepatic TG and plasma insulin without altering caloric intake, body weight gain and fat mass.
长链脂肪酸在小肠中诱导载脂蛋白 A4（APOA4）的产生，并激活棕色脂肪组织（BAT）的产热作用。BAT 产热作用的增加可增强甘油三酯的清除和胰岛素敏感性。重组 APOA4 蛋白的急性给药可提高 Chow 喂养小鼠的 BAT 产热作用。然而，持续输注重组 APOA4 蛋白在调节低脂饮食（LFD）喂养小鼠的交感神经活性、产热作用以及脂质和葡萄糖代谢方面的生理作用仍不清楚。本研究的假设是，持续输注鼠 APOA4 蛋白将增加 BAT 和腹股沟皮下白色脂肪组织（IWAT）的交感神经活性和产热作用，降低血浆脂质水平，并改善葡萄糖耐量。为了验证这一假设，测量了 APOA4 或盐水处理的小鼠的交感神经活性、BAT 温度、能量消耗、体重、脂肪量、热量摄入、葡萄糖耐量以及 BAT 和 IWAT 产热和脂肪分解蛋白、血浆脂质和肝脏脂肪酸氧化标志物的水平。APOA4 处理组的血浆 APOA4 水平升高，BAT 温度和产热作用上调，血浆甘油三酯（TG）水平降低，而 APOA4 处理组和盐水处理组的体重、脂肪量、热量摄入、能量消耗以及血浆胆固醇和瘦素水平相当。此外，APOA4 输注刺激了 BAT 和肝脏中的交感神经活性，但没有刺激 IWAT 中的交感神经活性。APOA4 处理组小鼠的肝脏脂肪酸氧化增加，但 TG 含量减少。APOA4 处理组小鼠在葡萄糖挑战后的血浆胰岛素水平低于盐水处理组。总之，持续输注鼠 APOA4 蛋白可刺激 BAT 和肝脏中的交感神经活性，提高 BAT 产热和肝脏脂肪酸氧化作用，从而降低血浆和肝脏 TG 以及血浆胰岛素水平，而不改变热量摄入、体重增加和脂肪量。
