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Targeted overexpression of PPARγ in skeletal muscle by random insertion and CRISPR/Cas9 transgenic pig cloning enhances oxidative fiber formation and intramuscular fat deposition
Author(s) -
Gu Hao,
Zhou Ying,
Yang Jinzeng,
Li Jianan,
Peng Yaxin,
Zhang Xia,
Miao Yiliang,
Jiang Wei,
Bu Guowei,
Hou Liming,
Li Ting,
Zhang Lin,
Xia Xiaoliang,
Ma Zhiyuan,
Xiong Yuanzhu,
Zuo Bo
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001812rr
Subject(s) - intramuscular fat , peroxisome proliferator activated receptor , lipogenesis , endocrinology , medicine , skeletal muscle , adipogenesis , adipocyte , transgene , chemistry , microbiology and biotechnology , biology , lipid metabolism , receptor , adipose tissue , biochemistry , gene
Abstract Peroxisome proliferator‐activated receptor gamma (PPARγ) is a master regulator of adipogenesis and lipogenesis. To understand its roles in fiber formation and fat deposition in skeletal muscle, we successfully generated muscle‐specific overexpression of PPARγ in two pig models by random insertion and CRISPR/Cas9 transgenic cloning procedures. The content of intramuscular fat was significantly increased in PPARγ pigs while had no changes on lean meat ratio. PPARγ could promote adipocyte differentiation by activating adipocyte differentiating regulators such as FABP4 and CCAAT/enhancer‐binding protein (C/EBP), along with enhanced expression of LPL, FABP4, and PLIN1 to proceed fat deposition. Proteomics analyses demonstrated that oxidative metabolism of fatty acids and respiratory chain were activated in PPARγ pigs, thus, gathered more Ca 2+ in PPARγ pigs. Raising of Ca 2+ could result in increased phosphorylation of CAMKII and p38 MAPK in PPARγ pigs, which can stimulate MEF2 and PGC1α to affect fiber type and oxidative capacity. These results support that skeletal muscle‐specific overexpression of PPARγ can promote oxidative fiber formation and intramuscular fat deposition in pigs.