Lin Fangjun, Gilbertson Timothy A
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
bioRxiv. 2025 Mar 13:2025.03.12.642880. doi: 10.1101/2025.03.12.642880.
Taste is a major driving force that influences food choices and dietary intake. Adiponectin has been shown to selectively enhance cellular responses to fatty acids by mediating the activation of AMPK and translocation of CD36 in taste cells via its receptor AdipoR1. Whether gene knockout affects fat taste responsiveness and dietary fat intake in animals remains unclear. In the present study, we evaluated cellular, neural, and behavioral responses to fat, as well as the dietary fat intake in global knockout mice and their WT controls. Sex-specific changes in cellular and behavioral responses to fatty acid were observed in knockout mice. Linoleic acid (LA)-induced calcium responsiveness appears to be reduced in taste cells from -deficient males and increased in taste cells from -deficient females. Brief-access taste testing revealed a loss of fat taste behavioral responsiveness in naïve animals. Fat taste loss found in males was restored after fat exposure and showed no significant differences in taste behavioral responses to fatty acids with WT controls in two-bottle preference and conditioned taste aversion tests. females were found to have diminished preference for LA in two-bottle preference tests, lower intralipid/water lick ratio in a brief-access assay, and reduced avoidance for LA in conditioned taste aversion assay. Furthermore, the taste nerve responses to intralipid and the dietary fat intakes appeared to be the same between and WT mice. In the high-fat diet feeding study, females gained more weight, while no differences in body weight gain were found in males. Together, we show that adiponectin/AdipoR1 signaling plays crucial sex-specific roles in the modulation of fat taste and the maintenance of healthy body weight primarily by regulating energy expenditure rather than dietary fat intake in mice.
味觉是影响食物选择和饮食摄入的主要驱动力。脂联素已被证明可通过其受体AdipoR1介导味觉细胞中AMPK的激活和CD36的转位，从而选择性增强细胞对脂肪酸的反应。基因敲除是否会影响动物对脂肪的味觉反应性和饮食中的脂肪摄入量尚不清楚。在本研究中，我们评估了全局敲除小鼠及其野生型对照对脂肪的细胞、神经和行为反应，以及它们的饮食脂肪摄入量。在敲除小鼠中观察到了对脂肪酸的细胞和行为反应的性别特异性变化。亚油酸（LA）诱导的钙反应性在缺乏该基因的雄性小鼠的味觉细胞中似乎降低，而在缺乏该基因的雌性小鼠的味觉细胞中增加。短暂接触味觉测试显示，未接触过脂肪的敲除动物失去了对脂肪的味觉行为反应性。在脂肪暴露后，敲除雄性小鼠中发现的脂肪味觉丧失得以恢复，并且在两瓶偏好和条件性味觉厌恶测试中，其对脂肪酸的味觉行为反应与野生型对照无显著差异。在两瓶偏好测试中，敲除雌性小鼠对LA的偏好降低，在短暂接触试验中脂质/水舔舐比例较低，在条件性味觉厌恶试验中对LA的回避减少。此外，敲除小鼠和野生型小鼠之间对脂质的味觉神经反应和饮食脂肪摄入量似乎相同。在高脂饮食喂养研究中，敲除雌性小鼠体重增加更多，而雄性小鼠体重增加没有差异。总之，我们表明脂联素/AdipoR1信号通路在调节脂肪味觉和维持健康体重方面发挥着关键的性别特异性作用，主要是通过调节能量消耗而非小鼠的饮食脂肪摄入量来实现的。
