Lipocalin-type prostaglandin D2 synthase (L-PGDS) modulates beneficial metabolic effects of vertical sleeve gastrectomy

Background

Vertical  sleeve gastrectomy  (VSG) ameliorates metabolic complications in obese and  diabetic  patients through unknown mechanisms.

Objective

The objective of this study was to investigate the role of lipocalin-type  prostaglandin  D 2 synthase (L-PGDS) in  glucose  regulation in response to VSG using L-PGDS knock-out (KO),  knock-in  (KI), and  C57BL/6  (wild type) mice.

Setting

Winthrop University Hospital Research Institute.

Methods

Animals were divided into 6 groups: L-PGDS KO sham/VSG (n = 5), L-PGDS KI sham/VSG (n = 5), and C57BL/6 (wild type) sham/VSG (n = 5). Related parameters were measured in fasting animals after 10 weeks.

Results

Our intraperitoneal  glucose tolerance tests  and  homeostatic model assessment   insulin resistance  results showed significant  glycemic  improvement 10 weeks post-VSG in both C57BL/6 and KI groups compared with the sham group. In contrast, the KO group developed  glucose intolerance  and insulin resistance similar to or greater than the sham group 10 weeks post-VSG. Interestingly, weight gain was insignificant 10 weeks post-VSG in all the groups and even trended higher in the KO group compared with sham.  Peptide YY levels in the KO group post-VSG were slightly increased but significantly less than other groups. Similarly, the KO group showed significantly less  leptin  sensitivity in response to VSG compared with the KI group. Total cholesterol level remained unchanged in all groups irrespective of sham or surgery but interestingly, the KO group had significantly  higher cholesterol  levels. In parallel,  adipocyte  size was also found to be significantly increased in the KO group post-VSG compared with the sham group.

Conclusion

Our findings propose that L-PGDS plays an important role in the beneficial metabolic effects observed after VSG.