Department of Surgery, University of Michigan, Ann Arbor, MI, United States.
Department of Internal Medicine, Metabolism Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, United States.
Diabetes Metab. 2024 Sep;50(5):101570. doi: 10.1016/j.diabet.2024.101570. Epub 2024 Aug 10.
Optimal weight loss involves decreasing adipose tissue while preserving lean muscle mass. Identifying molecular mediators that preserve lean muscle mass is therefore a clinically important goal. We have shown that circulating, postprandial FGF19 levels are lower in patients with obesity and decrease further with comorbidities such as type 2 diabetes and MASLD. Preclinical studies have shown that FGF15 (mouse ortholog of human FGF19) is necessary to protect against lean muscle mass loss following metabolic surgery-induced weight loss in a mouse model of diet-induced obesity. We evaluated if non-surgical weight loss interventions also lead to increased systemic levels of FGF19 and whether FGF19 levels are predictive of lean muscle mass following rapid weight loss in human subjects with obesity.
Weight loss was induced in 176 subjects with obesity via a very low-energy diet, VLED (800 kcal/d) in the form of total liquid meal replacement for 3-4 months. We measured plasma FGF19 levels at baseline and following VLED-induced weight loss. Multiple linear regression was performed to assess if FGF19 levels were predictive of lean mass at baseline (obesity) and following VLED.
Postprandial levels of FGF19 increased significantly following VLED-weight loss. Multiple linear regression analysis showed that baseline (obesity) FGF19 levels, but not post VLED FGF19 levels, significantly predicted the percent of lean muscle mass after VLED-induced weight loss, while controlling for age, sex, and the baseline percent lean mass.
These data identify gut-muscle communication and FGF19 as a potentially important mediator of the preservation of lean muscle mass during rapid weight loss.
最佳的体重减轻涉及减少脂肪组织，同时保留瘦肌肉量。因此，确定保留瘦肌肉量的分子介质是一个具有临床重要意义的目标。我们已经表明，肥胖患者的循环餐后 FGF19 水平较低，并且随着 2 型糖尿病和 MASLD 等合并症进一步降低。临床前研究表明，FGF15（人类 FGF19 的鼠同源物）对于保护代谢手术后诱导的肥胖小鼠模型中的瘦肌肉量减轻是必要的。我们评估了非手术减肥干预是否也会导致全身性 FGF19 水平升高，以及 FGF19 水平是否可预测肥胖患者快速减肥后的瘦肌肉量。
通过极低能量饮食（VLED，800kcal/d），以全液体餐替代的形式，在 176 名肥胖患者中诱导体重减轻，持续 3-4 个月。我们在基线和 VLED 诱导的体重减轻后测量血浆 FGF19 水平。进行多元线性回归分析，以评估 FGF19 水平是否可预测基线（肥胖）和 VLED 后的瘦体重。
VLED 减肥后，餐后 FGF19 水平显著升高。多元线性回归分析表明，基线（肥胖）FGF19 水平，但不是 VLED 后 FGF19 水平，在控制年龄、性别和基线瘦体重百分比后，显著预测 VLED 诱导的体重减轻后瘦肌肉量的百分比。
这些数据确定了肠道-肌肉通讯和 FGF19 作为快速减肥过程中保留瘦肌肉量的潜在重要介质。
