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Sci Rep. 2018 May 17;8(1):7766. doi: 10.1038/s41598-018-25635-x.

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

Author information

1
Aging Biology in Health and Disease, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
2
Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
3
Japanese Center for Research on Women in Sport, Juntendo University Graduate School of Health and Sports Science, Chiba, 270-1695, Japan.
4
Department of Exercise Physiology, Juntendo University Graduate School of Health and Sports Science, Chiba, 270-1695, Japan.
5
Faculty of Pharmacy, Iwaki Meisei University, Fukushima, 970-8551, Japan.
6
Department of Clinical Laboratory medicine, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
7
Research Institute for Disease of Old Age, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
8
Aging Biology in Health and Disease, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. ehirasaw@juntendo.ac.jp.
9
Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. ehirasaw@juntendo.ac.jp.
10
Japanese Center for Research on Women in Sport, Juntendo University Graduate School of Health and Sports Science, Chiba, 270-1695, Japan. ehirasaw@juntendo.ac.jp.
11
Research Institute for Disease of Old Age, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. ehirasaw@juntendo.ac.jp.

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.

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