Lack of Syndecan-1 produces significant alterations in whole-body composition, metabolism and glucose homeostasis in mice

• 作者: Abdel Rahim A Hamad Anil Kumar Jaiswal Mohanraj Sadasivam Susan Aja
• 来源期刊: 世界糖尿病杂志:英文版(电子版)
• 学科: 医学
• 关键词: SYNDECAN-1 High fat diet Indirect CALORIMETRY Energy EXPENDITURE IL-17 FEEDING pattern
• 年，卷（期）: 2020,（4）
• 页码范围: 126-136
• 页数: 11页
• 分类号: R58

摘要

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.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.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 op