title: Novel phosphorylation of PPARγ ameliorates obesity-induced adipose tissue inflammation and improves insulin sensitivity.
abstract: Chronic inflammation in adipose tissue is highly associated with insulin resistance. Herein, we demonstrate that a novel modification of PPARγ is strongly associated with inflammatory responses in adipose tissue. c-Src kinase directly phosphorylated PPARγ at Tyr78, and this process was reversed by protein tyrosine phosphatase-1B (PTP-1B). In adipocytes, phosphorylation of PPARγ suppressed the expression of pro-inflammatory genes as well as the secretion of chemokines and cytokines, thus reducing macrophage migration. Importantly, pharmacological inhibition of c-Src kinase aggravated insulin resistance in obese mice with a concomitant increase in the expression of pro-inflammatory genes in adipose tissue. These data strongly suggest that PPARγ phosphorylation is the key regulatory mechanism of the inflammatory response in adipose tissue, which is highly associated with glucose tolerance and insulin sensitivity. Furthermore, these data increase our understanding of the mechanical aspects of developing novel anti-diabetic drugs targeting PPARγ phosphorylation.
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Sunsil
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Jung
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Yong Ryoul
authors.initials: YR
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Eung-Kyun
authors.initials: EK
authors.lastname: Kim
authors.affiliation: UNIST Central Research Facilities, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Il Shin
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Joong Kwan
authors.initials: JK
authors.lastname: Kim
authors.affiliation: UNIST Central Research Facilities, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Seo
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea. Electronic address: janghchoi@unist.ac.kr.
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Choi
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D000067996:RAW 264.7 Cells; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D018925:Chemokines; D047495:PPAR gamma; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Inflammation; Metabolic disorders; PPARγ; PTP-1B; Phosphorylation; c-Src