Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2020; 11(4): 126-136
Published online Apr 15, 2020. doi: 10.4239/wjd.v11.i4.126
Lack of Syndecan-1 produces significant alterations in whole-body composition, metabolism and glucose homeostasis in mice
Anil Kumar Jaiswal, Mohanraj Sadasivam, Susan Aja, Abdel Rahim A Hamad
Anil Kumar Jaiswal, Department of Pathobiology, Johns Hopkins University, Baltimore, MD 21205, United States
Mohanraj Sadasivam, Abdel Rahim A Hamad, Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States
Susan Aja, Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, United States
Author contributions: Jaiswal AK and Sadasivam M participated equally in the design, execution of the experiments and analysis of the data; Jaiswal AK, Sadasivam M, Aja S and Hamad ARA interpreted the data, and wrote the paper.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Johns Hopkins University Animal Care and Use Committee, in compliance with the Animal Welfare Act and principles set forth in the Guide for the Care and Use of Laboratory Animals.
Conflict-of-interest statement: Authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Abdel Rahim A Hamad, PhD, Associate Professor, Department of Pathology, Johns Hopkins University School of Medicine, Ross 66G, 720 Rutland Ave, Baltimore, MD 21205, United States. ahamad@jhmi.edu
Received: October 23, 2019
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
Abstract
BACKGROUND

Obesity is a disease state with serious adverse metabolic complications, including glucose intolerance and type 2 diabetes that currently has no cure. Identifying and understanding roles of various modulators of body composition and glucose homeostasis is required for developing effective cures. 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 little is known about its roles in regulating obesity and glucose homeostasis.

AIM

To examine the role of Sdc1 in regulating body fat and glucose metabolism.

METHODS

We used female wild type and Sdc1 knockout (Sdc1 KO) mice on BALB/c background and multiple methods. Metabolic measurements (rates of oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure) 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.

RESULTS

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. Sdc1KO 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.

CONCLUSION

These results reveal critical multisystem and opposing roles for Sdc1 in regulating normal energy balance and glucose homeostasis. The results will have important implications for targeting Sdc1 to modulate metabolic parameters. Finally, we offer a novel hypothesis that could reconcile the opposing roles associated with Sdc1 deficiency.

Keywords: Syndecan-1, High fat diet, Indirect calorimetry, Energy expenditure, IL-17, Feeding pattern

Core tip: Obesity is a disease state with serious adverse metabolic complications that currently has no cure. Identifying key modulators is required for developing effective cures. Here we investigated Syndecan-1 (Sdc1), a member of the heparan sulfate proteoglycan family for its roles in regulating obesity and glucose homeostasis. Sdc1 knockout (Sdc1 KO) mice have reduced body weight with 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. Our results reveal critical multisystem and opposing roles for Sdc1 in regulating normal energy balance and glucose homeostasis.