TY - JOUR
T1 - Hepatic overexpression of protein targeting to glycogen attenuates obesity and improves hyperglycemia in db/db mice
AU - López-Soldado, Iliana
AU - Guinovart, Joan J.
AU - Duran, Jordi
N1 - Funding Information:
This study was supported by grants from the Spanish Ministry of Science, Innovation, and Universities (MCIU/FEDER/AEI) (BFU2017-84345-P to JG and JD and PID2020-118699GB-I00 to JD), the CIBER de Diabetes y Enfermedades Metabólicas Asociadas (ISCIII, Ministerio de Ciencia e Innovación), and “La Marató de TV3” Foundation (Barcelona, Spain) (project 201613-10). We gratefully acknowledge institutional funding from the Spanish Ministry of Science and Innovation through the Centres of Excellence Severo Ochoa Award and from the CERCA Programme/Generalitat de Catalunya.
Publisher Copyright:
Copyright © 2022 López-Soldado, Guinovart and Duran.
PY - 2022/9/9
Y1 - 2022/9/9
N2 - Increased liver glycogen content has been shown to reduce food intake, attenuate obesity, and improve glucose tolerance in a mouse model of high-fat diet (HFD)-induced obesity. Here we studied the contribution of liver glycogen to the regulation of obesity and glucose metabolism in a model of type 2 diabetes and obesity, namely the db/db mouse. To this end, we crossed db/db mice with animals overexpressing protein targeting to glycogen (PTG) in the liver to generate db/db mice with increased liver glycogen content (db/db-PTG). Hepatic PTG overexpression reduced food intake and fat weight and attenuated obesity and hyperglycemia in db/db mice. Db/db-PTG mice showed similar energy expenditure and physical activity to db/db mice. PTG overexpression reduced liver phosphoenolpyruvate carboxykinase (PEPCK) protein levels and repressed hepatic glucose production in db/db mice. Moreover, increased liver glycogen elevated hepatic ATP content in these animals. However, lipid metabolism was not modified by PTG overexpression. In conclusion, increased liver glycogen content ameliorates the diabetic and obesity phenotype in db/db mice.
AB - Increased liver glycogen content has been shown to reduce food intake, attenuate obesity, and improve glucose tolerance in a mouse model of high-fat diet (HFD)-induced obesity. Here we studied the contribution of liver glycogen to the regulation of obesity and glucose metabolism in a model of type 2 diabetes and obesity, namely the db/db mouse. To this end, we crossed db/db mice with animals overexpressing protein targeting to glycogen (PTG) in the liver to generate db/db mice with increased liver glycogen content (db/db-PTG). Hepatic PTG overexpression reduced food intake and fat weight and attenuated obesity and hyperglycemia in db/db mice. Db/db-PTG mice showed similar energy expenditure and physical activity to db/db mice. PTG overexpression reduced liver phosphoenolpyruvate carboxykinase (PEPCK) protein levels and repressed hepatic glucose production in db/db mice. Moreover, increased liver glycogen elevated hepatic ATP content in these animals. However, lipid metabolism was not modified by PTG overexpression. In conclusion, increased liver glycogen content ameliorates the diabetic and obesity phenotype in db/db mice.
KW - ATP
KW - db/db
KW - food intake
KW - glucose
KW - glycogen
KW - liver
UR - http://www.scopus.com/inward/record.url?scp=85138831538&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000872931000001&DestLinkType=FullRecord&DestApp=WOS_CPL
UR - http://hdl.handle.net/20.500.14342/4464
U2 - 10.3389/fendo.2022.969924
DO - 10.3389/fendo.2022.969924
M3 - Article
C2 - 36157460
AN - SCOPUS:85138831538
SN - 1664-2392
VL - 13
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 969924
ER -