Jeromson Stewart, Akcan Michael, Baranowski Bradley, Arbeau Meagan, Bellucci Annalaura, Wright David C
School of Kinesiology, University of British Columbia, Vancouver, BC, Canada.
Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC, Canada.
J Physiol. 2024 Dec;602(24):6813-6826. doi: 10.1113/JP287256. Epub 2024 Nov 9.
Growth differentiation factor 15 (GDF15) is a stress-induced cytokine that suppresses food intake and causes weight loss. GDF15 also reduces voluntary physical activity and, thus, it is not clear whether combining GDF15 with exercise will be beneficial or if reductions in food intake would be offset by decreases in physical activity. We investigated how GDF15 treatment combined with voluntary wheel running (VWR) would impact weight gain, food intake, adiposity and indices of metabolic health in mice. High-fat fed male and female mice underwent daily GDF15 treatments and were given access to voluntary running wheels, or not, for 11 days. In both sexes, VWR prevented weight gain. In males, GDF15 reduced food intake, as well as attenuated weight gain and the accumulation of adipose tissue, with no additional effect of VWR. In female mice, GDF15 did not impact body weight gain or body composition. GDF15 acutely reduced food intake in female mice but this was followed by a period of rebound hyperphagia and consequently GDF15 did not reduce total food intake in female mice. GDF15 treatment reduced wheel running distance in both sexes. There were main effects of VWR to improve glucose tolerance in female but not male mice. These findings show that GDF15 has sex-specific effects on food intake and consequently weight gain and adiposity. There is no added benefit of combining GDF15 and voluntary physical activity for weight loss. Adaptive responses to acute caloric restriction induced by GDF15 might limit its effectiveness as a weight loss tool in females. KEY POINTS: GDF15 is a stress-induced signalling factor that reduces food intake and voluntary physical activity. It is not known whether combining GDF15 treatment with voluntary wheel running would impart beneficial combined effects in attenuating weight gain and the accumulation of adipose tissue. In the present study, we demonstrate that GDF15 reduces food intake and prevents weight gain in male but not female mice consuming a high-fat diet and also that combining GDF15 with voluntary wheel running (VWR) does not lead to a greater dampening of weight gain. In female mice, GDF15 acutely reduced food intake, but this was followed by a period of rebound hyperphagia resulting in no differences in total food intake. In both sexes, VWR was equivalent, or superior to GDF15 in preventing weight gain.
生长分化因子15（GDF15）是一种应激诱导的细胞因子，可抑制食物摄入并导致体重减轻。GDF15还会减少自主身体活动，因此，尚不清楚将GDF15与运动相结合是否有益，或者食物摄入量的减少是否会被身体活动的减少所抵消。我们研究了GDF15治疗与自主转轮运动（VWR）相结合如何影响小鼠的体重增加、食物摄入、肥胖及代谢健康指标。高脂喂养的雄性和雌性小鼠每天接受GDF15治疗，并给予或不给予自主转轮，持续11天。在两性中，VWR均能防止体重增加。在雄性小鼠中，GDF15减少了食物摄入，减轻了体重增加和脂肪组织的积累，VWR没有额外作用。在雌性小鼠中，GDF15对体重增加或身体组成没有影响。GDF15可急性减少雌性小鼠的食物摄入，但随后会出现一段时间的反弹性多食，因此GDF15并未减少雌性小鼠的总食物摄入量。GDF15治疗减少了两性的转轮运动距离。VWR对改善雌性而非雄性小鼠的葡萄糖耐量有主要作用。这些发现表明，GDF15对食物摄入以及体重增加和肥胖有性别特异性影响。将GDF15与自主身体活动相结合对减肥没有额外益处。对GDF15诱导的急性热量限制的适应性反应可能会限制其作为女性减肥工具的有效性。要点：GDF15是一种应激诱导的信号因子，可减少食物摄入和自主身体活动。尚不清楚将GDF15治疗与自主转轮运动相结合是否会在减轻体重增加和脂肪组织积累方面产生有益的联合作用。在本研究中，我们证明，GDF15可减少高脂饮食雄性小鼠而非雌性小鼠的食物摄入并防止体重增加，并且将GDF15与自主转轮运动（VWR）相结合不会导致更大程度的体重增加减轻。在雌性小鼠中，GDF15可急性减少食物摄入，但随后会出现一段时间的反弹性多食，导致总食物摄入量无差异。在两性中，VWR在防止体重增加方面等同于或优于GDF15。
