Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Endocrinology. 2018 Jul 1;159(7):2676-2682. doi: 10.1210/en.2018-00307.
Leptin has been the only known homeostatic regulator of fat mass, but we recently found evidence for a second one, named the gravitostat. In the current study, we compared the effects of leptin and increased loading (gravitostat stimulation) on fat mass in mice with different levels of body weight (lean, overweight, and obese). Leptin infusion suppressed body weight and fat mass in lean mice given normal chow but not in overweight or obese mice given a high-fat diet for 4 and 8 weeks, respectively. The maximum effect of leptin on body weight and fat mass was obtained already at <44 ng/mL of serum leptin. Increased loading using intraperitoneal capsules with different weights decreased body weight in overweight and obese mice. Although the implantation of an empty capsule reduced the body weight in lean mice, only a nonsignificant tendency of a specific effect of increased loading was observed in the lean mice. These findings demonstrate that the gravitostat regulates fat mass in obese mice, whereas leptin regulates fat mass only in lean mice with low endogenous serum leptin levels. We propose that activation of the gravitostat primarily protects against obesity, whereas low levels of leptin protect against undernutrition.
瘦素一直是脂肪量的唯一已知的体内平衡调节剂，但我们最近发现了第二种调节剂，名为重力稳定器。在目前的研究中，我们比较了瘦素和增加负荷（重力稳定器刺激）对不同体重水平（瘦、超重和肥胖）的小鼠脂肪量的影响。瘦素输注抑制了正常饮食喂养的瘦小鼠的体重和脂肪量，但不能抑制高脂饮食喂养 4 周和 8 周的超重或肥胖小鼠的体重和脂肪量。血清瘦素<44ng/mL 时，瘦素对体重和脂肪量的最大作用已经达到。使用不同重量的腹腔胶囊增加负荷可降低超重和肥胖小鼠的体重。虽然植入空胶囊会降低瘦小鼠的体重，但在瘦小鼠中仅观察到增加负荷的特定效应的趋势不显著。这些发现表明，重力稳定器调节肥胖小鼠的脂肪量，而瘦素仅调节低内源性血清瘦素水平的瘦小鼠的脂肪量。我们提出，重力稳定器的激活主要可预防肥胖，而低水平的瘦素可预防营养不良。
