Key result
Roux-en-Y gastric bypass surgery reduced hepatic lipid content and adiposity while increasing energy expenditure and lean body mass relative to weight-matched calorie restriction in mice.
Why the study?
Obesity drives NAFLD, and weight-loss interventions like bariatric surgery or calorie restriction may be effective therapies, prompting a comparison of their effects on hepatic function.
Does Roux-en-Y gastric bypass surgery improve hepatic lipid homeostasis more than weight-matched calorie restriction in a mouse model of obesity and NAFLD?
RCT
Randomized to sham surgery, RYGB, or CR weight matched to RYGB
Does Roux-en-Y gastric bypass surgery improve hepatic lipid homeostasis more than weight-matched calorie restriction in a mouse model of obesity and NAFLD?
Roux-en-Y gastric bypass surgery provides weight-independent benefits on hepatic lipid homeostasis and transcriptome remodeling compared to calorie restriction in a mouse model of NAFLD.
Hypothesis-generating for RYGB benefits beyond weight loss in obesity; should not change clinical practice.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Axelrod et al. (2023) conducted an RCT in Obesity and non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass surgery (RYGB) vs. Sham surgery and weight-matched calorie restriction (CR) was evaluated on Hepatic function, lipid content, and adiposity. Roux-en-Y gastric bypass surgery reduced hepatic lipid content and adiposity while increasing energy expenditure and lean body mass relative to weight-matched calorie restriction in mice.
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