Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-25635-x
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Funding
- Ministry of Education, Culture, Sports, Science and Technology [MEXT: 15K09326]
- Japan Agency for Medical Research and Development [AMED: 17ek0109230s0101]
- Intramural Research Grant for Neurological and Psychiatric Disorders of National Center of NCNP [29-4]
- Grants-in-Aid for Scientific Research [16K15268] Funding Source: KAKEN
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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(-1-)-Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WTTg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2(-1-)-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(-1-)-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(-1-)-Tg mice. Furthermore, the perlecan-deficient skeletal muscle also had elevated levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCl alpha) protein. PGCl alpha 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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