Prophylactic sleeve gastrectomy (SG) in lean mice protects against Non-Alcoholic Steato-Hepatitis (NASH) and Type 2 Diabetes (T2D)
Andrei Moscalu1, James N. Luo1, Renuka S. Haridas1, Cullen Roberts1, Mehran Karvar1, Yingjia Chen1, Ali Tavakkoli1, Eric G. Sheu1 & David A. Harris1
1Laboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Boston, MA
NASH, T2D and obesity are closely linked. SG, the most performed metabolic surgery in the United States, leads to durable improvements in T2D and significantly improves NASH. Here we test SG effectiveness in preventing T2D and NASH associated with future diet-induced obesity.
Thirty-four, 12-week-old, lean, male C57BL/6J mice underwent SG or Sham surgery and were initially maintained on a normal diet. At day 60 post-op, all mice were transitioned to 60%-High-Fat-Diet (HFD) and followed to day 140 post-op. Pre- and post-transition to HFD, weight, body composition, food intake, oral glucose tolerance, insulin tolerance, whole animal metabolic caging measurements, liver lipid content & histology, fecal lipid content & bomb calorimetry were assessed.
Following SG, lean mice on low-fat diet do not have sustained weight loss. However, after transition to HFD, SG mice gain less weight (64.17%vs.91.67%), exhibit improved glucose and insulin-tolerance, and were protected from hepatomegaly & hepatic steatosis as compared to shams (Figure-1A-C). These changes occur despite no difference in food intake or lipid absorption. Indirect calorimetry revealed that SG increased energy expenditure and induced a shift toward host lipid utilization. This was associated with decreased fecal caloric excretion (Figure-1D&E).
SG in lean mice protects against the development of NASH and T2D associated with future weight gain by inducing a shift toward lipid utilization with a concomitant increase in energy expenditure.
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