Published online Apr 15, 2020. doi: 10.4239/wjd.v11.i4.126
Peer-review started: October 23, 2019
First decision: December 12, 2019
Revised: December 20, 2019
Accepted: February 8, 2020
Article in press: February 8, 2020
Published online: April 15, 2020
Obesity is a disease state with serious adverse metabolic complications that currently has no cure. Attempts to control obesity by altering lifestyle has no significant improvement in most individuals. Therefore, it is necessary to discover alternative strategies to combat obesity and its complications.
Syndecan-1 (Sdc1) is a member of the heparan sulfate proteoglycan family that has mainly been investigated for its role in regulating proliferation and survival of epithelia and tumor cells, but its roles in regulating obesity and glucose homeostasis are not well study.
The objective of this study is to examine the role of Sdc1 in regulating body fat and glucose metabolism.
We used female wild type and Sdc1 knockout (Sdc1 KO) mice on BALB/c background and multiple methods. Metabolic measurements were performed using an open-flow indirect calorimeter with additional features to measure food intake and physical activity. Glucose intolerance and insulin resistance were measured by established tolerance test methods.
Although our primary goal was to investigate the effects of Sdc1 deficiency on body fat and glucose homeostasis, we uncovered that Sdc1 regulates multiple metabolic parameters. Sdc1 KO mice have reduced body weight due to significant decreases in fat and lean masses under both chow and high fat diet conditions. The reduced body weight was not due to changes in food intakes, but Sdc1 KO mice exhibited altered feeding behavior as they ate more during the dark phase and less during the light phase than wild type mice. In addition, Sdc1 KO mice suffered from high rate of energy expenditure, glucose intolerance and insulin resistance.
These results reveal critical multisystem and opposing roles for Sdc1 in regulating normal energy balance and glucose homeostasis.
The results provide important insights that will guide future strategies to target syndecan-1 for immunotherapy for obesity.