Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Am J Physiol Endocrinol Metab. 2022 Jun 1;322(6):E494-E507. doi: 10.1152/ajpendo.00432.2021. Epub 2022 Apr 11.
Binge-eating disorder is the most prevalent eating disorder diagnosed, affecting three times more women than men. Ghrelin stimulates appetite and reward signaling, and loss of its receptor reduces binge-eating behavior in male mice. Here, we examined the influence of ghrelin itself on binge-eating behavior in both male and female mice. Five-wk-old wild-type (WT) and ghrelin-deficient () mice were housed individually in indirect calorimetry cages for 9 wks. Binge-like eating was induced by giving mice ad libitum chow, but time-restricted access to a Western-style diet (WD; 2 h access, 3 days/wk) in the light phase (BE); control groups received ad libitum chow (CO), or ad libitum access to both diets (CW). All groups of BE mice showed binge-eating behavior, eating up to 60% of their 24-h intake during the WD access period. Subsequent dark phase chow intake was decreased in mice and remained decreased in females on nonbinge days. Also, nonbinge day locomotor activity was lower in than in WT BE females. Upon euthanasia, BE mice weighed less and had a lower lean body mass percentage than WT BE mice. In BE and CW groups, ghrelin and sex altered the expression of genes involved in lipid processing, thermogenesis, and aging in white adipose tissue and livers. We conclude that, although ghrelin deficiency does not hamper the development of binge-like eating, it sex-dependently alters food intake timing, locomotor activity, and metabolism. These results add to the growing body of evidence that ghrelin signaling is sexually dimorphic. Ghrelin, a peptide hormone secreted from the gut, is involved in hunger and reward signaling, which are altered in binge-eating disorder. Although sex differences have been described in both binge-eating and ghrelin signaling, this interaction has not been fully elucidated. Here, we show that ghrelin deficiency affects the behavior and metabolism of mice in a binge-like eating paradigm, and that the sex of the mice impacts the magnitude and direction of these effects.
暴食症是最常见的饮食失调症，女性患者是男性的三倍。胃饥饿素刺激食欲和奖励信号，其受体的缺失会减少雄性小鼠的暴食行为。在这里，我们研究了胃饥饿素本身对雄性和雌性小鼠暴食行为的影响。将 5 周龄野生型（WT）和胃饥饿素缺失（）小鼠单独饲养在间接测热笼中 9 周。通过给予小鼠自由进食标准饮食（chow），诱导暴食样进食，但是在光照期限制进食西式饮食（Western-style diet，WD；2 h 进食，每周 3 天）（BE）；对照组给予自由进食标准饮食（CO）或两种饮食的自由进食（CW）。所有 BE 组的小鼠都表现出暴食行为，在 WD 进食期间摄入高达 24 h 总摄入量的 60%。随后，在非暴食日，的雄性和雌性小鼠的夜间 chow 摄入量减少。此外，非暴食日的运动活动在雌性中的减少。与 WT BE 雌性相比，BE 雄性的体重较轻，瘦体重百分比较低。在安乐死时，与 WT BE 雄性相比，BE 雄性的体重较轻，瘦体重百分比较低。在 BE 和 CW 组中，ghrelin 和性别改变了白色脂肪组织和肝脏中参与脂质处理、产热和衰老的基因的表达。我们的结论是，尽管胃饥饿素缺乏不会阻碍暴食样进食的发展，但它以性别依赖的方式改变了食物摄入的时间、运动活动和代谢。这些结果增加了越来越多的证据表明，ghrelin 信号是有性别差异的。胃饥饿素是一种从肠道分泌的肽激素，参与饥饿和奖励信号，在暴食症中这些信号被改变。尽管在暴食和胃饥饿素信号中都描述了性别差异，但这种相互作用尚未完全阐明。在这里，我们表明胃饥饿素缺乏会影响小鼠在暴食样进食模型中的行为和代谢，并且小鼠的性别会影响这些影响的程度和方向。
