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Perlecan, a Heparan Sulfate Proteoglycan, Regulates Systemic Metabolism With Dynamic Changes in Adipose Tissue and Skeletal Muscle

Perlecan, a Heparan Sulfate Proteoglycan, Regulates Systemic Metabolism With Dynamic Changes in Adipose Tissue and Skeletal Muscle

Yuri Yamashita, Satoshi Nakada, Toshinori Yoshihara, Takeshi Nara, Norihiko Furuya, Takashi Miida, Nobutaka Hattori, Eri Arikawa-Hirasawa

Sci Rep. 2018 May 17;8(1):7766.

PMID: 29773865

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 composition to oxidative fibers. Our data suggest that downregulation of perlecan is a promising strategy to control metabolic syndrome.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4241166	Heparan sulfate proteoglycan			Price

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