Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with dynamic changes in adipose tissue and skeletal muscle

Scientific Reports
Yuri YamashitaEri Arikawa-Hirasawa

Abstract

Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2-/--Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2-/--Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation. In addition, the Hspg2-/--Tg mice demonstrated increased insulin sensitivity. Molecular analysis revealed the significantly relatively increased amount of the muscle fiber type IIA (X) isoform and a larger quantity of mitochondria in the skeletal muscle of Hspg2-/--Tg mice. Furthermore, the perlecan-deficient skeletal muscle also had elevated levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) protein. PGC1α expression is activated by exercise, and induces mitochondrial biosynthesis. Thus, perlecan may act as a mechano-regulator of catabolism of both lipids and glucose by shifting the muscle fiber composi...Continue Reading

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Citations

Apr 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rocío Guzmán-RuizMaría M Malagón
Jun 9, 2020·Frontiers in Immunology·Ariane R PessentheinerPhilip L S M Gordts
Oct 7, 2020·The Journal of Biological Chemistry·Carolyn G Chen, Renato V Iozzo
Feb 13, 2021·International Journal of Molecular Sciences·María Julia BarisónBruno Dallagiovanna
Feb 19, 2021·Journal of Applied Physiology·Toshinori YoshiharaHisashi Naito
Jan 18, 2021·The Journal of Biological Chemistry·Carolyn G Chen, Renato V Iozzo
Dec 2, 2019·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Jared DeyarminJane Khudyakov
Apr 2, 2021·Seminars in Thrombosis and Hemostasis·Linda M Hiebert
Sep 21, 2020·Progress in Retinal and Eye Research·Sayon Roy, Dongjoon Kim
Oct 15, 2020·Cellular and Molecular Life Sciences : CMLS·Esther HermanoMichael Elkin
Dec 5, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Heidi N du PreezJohnson Lin
Jan 5, 2022·Open Biology·Carolyn G Chen, Renato V Iozzo

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Methods Mentioned

BETA
electrophoresis
transgenic

Software Mentioned

GraphPad Prism
ImageJ

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