posted on 2021-08-02, 18:42authored byRachel Ben-Haroush Schyr, Abbas Al-Kurd, Botros Moalem, Anna Permyakova, Hadar Israeli, Aya Bardugo, Liron Hefetz, Michael Bergel, Arnon Haran, Shahar Azar, Itia Magenheim, Joseph Tam, Ronit Grinbaum, Danny Ben-Zvi
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.
Funding
This study was supported by ERC StG (803526) awarded to DBZ, and an Israel Science Foundation (ISF) grant (158/18) to JT. DBZ is a Zuckerman faculty fellow.