Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
Obesity (Silver Spring). 2023 Dec;31(12):2960-2971. doi: 10.1002/oby.23876. Epub 2023 Sep 20.
Obesity is a driver of non-alcoholic fatty liver disease (NAFLD), and interventions that decrease body weight, such as bariatric surgery and/or calorie restriction (CR), may serve as effective therapies. This study compared the effects of Roux-en-Y gastric bypass surgery (RYGB) and CR on hepatic function in mice with obesity and NAFLD.
C57BL/6J mice were fed a high-fat diet to promote obesity. At 16 weeks of age, mice were randomized to sham surgery (sham), RYGB, or CR weight matched to RYGB (WM). Body weight/composition, food intake, and energy expenditure (EE) were measured throughout treatment. Liver histopathology was evaluated from H&E-stained sections. Hepatic enzymes and glycogen content were determined by ELISA. Transcriptional signatures were revealed via RNA sequencing.
RYGB reduced hepatic lipid content and adiposity while increasing EE and lean body mass relative to WM. Hepatic glycogen and bile acid content were increased after RYGB relative to sham and WM. RYGB activated enterohepatic signaling and genes regulating hepatic lipid homeostasis.
RYGB improved whole-body composition and hepatic lipid homeostasis to a greater extent than CR in mice. RYGB was associated with discrete remodeling of the hepatic transcriptome, suggesting that surgery may be mechanistically additive to CR.
肥胖是导致非酒精性脂肪性肝病（NAFLD）的一个因素，而减轻体重的干预措施，如减重手术和/或热量限制（CR），可能是有效的治疗方法。本研究比较了肥胖合并 NAFLD 小鼠中 Roux-en-Y 胃旁路手术（RYGB）和 CR 对肝功能的影响。
C57BL/6J 小鼠喂食高脂肪饮食以促进肥胖。在 16 周龄时，将小鼠随机分为假手术（sham）、RYGB 和与 RYGB 体重匹配的 CR（WM）组。在整个治疗过程中测量体重/成分、食物摄入量和能量消耗（EE）。通过 H&E 染色切片评估肝组织病理学。通过 ELISA 测定肝酶和糖原含量。通过 RNA 测序揭示转录特征。
RYGB 与 WM 相比，降低了肝脂质含量和脂肪堆积，同时增加了 EE 和瘦体重。与 sham 和 WM 相比，RYGB 后肝糖原和胆汁酸含量增加。RYGB 激活了肠肝信号转导和调节肝脂质稳态的基因。
RYGB 改善了全身成分和肝脂质稳态，比 CR 更显著。RYGB 与肝转录组的离散重塑有关，表明手术可能与 CR 具有机制上的相加作用。
