Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight-Loss

Bariatric surgeries induce weight loss which is associated with an improvement in hepatic steatosis and reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight-loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet, and compared them to diet and weight-matched sham-operated mice (WMS). 40 days after surgery, VSG-operated mice displayed lesser hepatic steatosis compared to WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through weight-loss and diet-independent mechanisms.