Diabetes Institute and Honor Tutorial College, Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH 45221, USA.
Int J Mol Sci. 2021 Jan 27;22(3):1221. doi: 10.3390/ijms22031221.
Stimulation of thermogenesis in brown adipose tissue (BAT) could have far-reaching health benefits in combatting obesity and obesity-related complications. Apolipoprotein A-IV (ApoA-IV), produced by the gut and the brain in the presence of dietary lipids, is a well-known short-term satiating protein. While our previous studies have demonstrated reduced diet-induced thermogenesis in ApoA-IV-deficient mice, it is unclear whether this reduction is due to a loss of peripheral or central effects of ApoA-IV. We hypothesized that central administration of ApoA-IV stimulates BAT thermogenesis and that sympathetic and sensory innervation is necessary for this action. To test this hypothesis, mice with unilateral denervation of interscapular BAT received central injections of recombinant ApoA-IV protein or artificial cerebrospinal fluid (CSF). The effects of central ApoA-IV on BAT temperature and thermogenesis in mice with unilateral denervation of the intrascapular BAT were monitored using transponder probe implantation, qPCR, and immunoblots. Relative to CSF, central administration of ApoA-IV significantly increased temperature and UCP expression in BAT. However, all of these effects were significantly attenuated or prevented in mice with unilateral denervation. Together, these results clearly demonstrate that ApoA-IV regulates BAT thermogenesis centrally, and this effect is mediated through sympathetic and sensory nerves.
刺激棕色脂肪组织（BAT）的产热作用可能在对抗肥胖和肥胖相关并发症方面具有深远的健康益处。载脂蛋白 A-IV（ApoA-IV）在存在膳食脂质的情况下由肠道和大脑产生，是一种众所周知的短期饱腹感蛋白。虽然我们之前的研究表明 ApoA-IV 缺陷小鼠的饮食诱导产热减少，但不清楚这种减少是由于 ApoA-IV 的外周或中枢作用丧失所致。我们假设中枢给予 ApoA-IV 可刺激 BAT 产热，而交感神经和感觉神经支配对于这种作用是必需的。为了验证这一假设，我们对肩胛间 BAT 单侧去神经的小鼠进行了中央注射重组 ApoA-IV 蛋白或人工脑脊液（CSF）。使用转发器探针植入、qPCR 和免疫印迹监测中央 ApoA-IV 对肩胛间 BAT 单侧去神经小鼠的 BAT 温度和产热的影响。与 CSF 相比，中枢给予 ApoA-IV 可显著增加 BAT 的温度和 UCP 表达。然而，这些影响在单侧去神经的小鼠中明显减弱或被阻止。综上所述，这些结果清楚地表明，ApoA-IV 从中枢调节 BAT 产热，这种作用是通过交感神经和感觉神经介导的。
