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2018 ; 8
(1
): 7766
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English Wikipedia
Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with
dynamic changes in adipose tissue and skeletal muscle
#MMPMID29773865
Yamashita Y
; Nakada S
; Yoshihara T
; Nara T
; Furuya N
; Miida T
; Hattori N
; Arikawa-Hirasawa E
Sci Rep
2018[May]; 8
(1
): 7766
PMID29773865
show ga
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 (PGC1?) protein. PGC1? 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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