Morrison Christopher D, Hao Zheng, Mumphrey Michael B, Townsend R Leigh, Münzberg Heike, Ye Jianping, Berthoud Hans-Rudolf
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Mol Metab. 2016 Aug 16;5(10):1006-1014. doi: 10.1016/j.molmet.2016.08.005. eCollection 2016 Oct.
The mechanisms by which bariatric surgeries so effectively and lastingly reduce body weight and normalize metabolic dysfunction are not well understood. Fibroblast growth fator-21 (FGF21) is a key regulator of metabolism and is currently considered for treatment of obesity. Although elevated by acute food deprivation, it is downregulated after weight loss induced by chronic calorie restriction but not after Roux-en-Y gastric bypass surgery. Therefore, the goal of the present study was to assess the role of FGF21-signaling in the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB).
High-fat diet-induced obese FGF21-deficient (FGF21(-/-)) and wildtype (WT) mice were subjected to RYGB, sham surgery, or caloric restriction to match body weight of RYGB mice. Body weight, body composition, food intake, energy expenditure, glucose tolerance, and insulin sensitivity, as well as plasma levels and hepatic mRNA expression of FGF21 were measured.
Hepatic expression and plasma levels of FGF21 are higher after RYGB compared with similar weight loss induced by caloric restriction, suggesting that elevated FGF21 might play a role in preventing increased hunger and weight regain after RYGB. However, although the body weight differential between RYGB and sham surgery was significantly reduced in FGF21(-/-) mice, RYGB induced similarly sustained body weight and fat mass loss, initial reduction of food intake, increased energy expenditure, and improvements in glycemic control in FGF21(-/-) and WT mice.
FGF21 signaling is not a critical single factor for the beneficial metabolic effects of RYGB. This may open up the possibility to use FGF21 as adjuvant therapy in patients with ineffective bariatric surgeries.
减肥手术能如此有效且持久地减轻体重并使代谢功能恢复正常的机制尚未完全明确。成纤维细胞生长因子-21（FGF21）是代谢的关键调节因子，目前正被考虑用于治疗肥胖症。尽管急性食物剥夺会使其升高，但在慢性热量限制导致体重减轻后它会下调，而在Roux-en-Y胃旁路手术后则不会。因此，本研究的目的是评估FGF21信号通路在Roux-en-Y胃旁路手术（RYGB）的有益作用中的作用。
将高脂饮食诱导的肥胖FGF21缺陷型（FGF21(-/-)）和野生型（WT）小鼠进行RYGB手术、假手术或热量限制，以使体重与RYGB小鼠相匹配。测量体重、身体组成、食物摄入量、能量消耗、葡萄糖耐量和胰岛素敏感性，以及FGF21的血浆水平和肝脏mRNA表达。
与热量限制导致的相似体重减轻相比，RYGB术后肝脏FGF21表达和血浆水平更高，这表明升高的FGF21可能在预防RYGB术后饥饿增加和体重反弹中起作用。然而，尽管FGF21(-/-)小鼠中RYGB与假手术之间的体重差异显著减小，但RYGB在FGF21(-/-)和WT小鼠中同样能持续减轻体重和脂肪量、最初减少食物摄入量、增加能量消耗并改善血糖控制。
FGF21信号通路不是RYGB有益代谢作用的关键单一因素。这可能为在减肥手术无效的患者中使用FGF21作为辅助治疗开辟可能性。
