title: Phloretin promotes adipocyte differentiation in vitro and improves glucose homeostasis in vivo.
abstract: Adipocyte dysfunction is associated with many metabolic diseases such as obesity, insulin resistance and diabetes. Previous studies found that phloretin promotes 3T3-L1 cells differentiation, but the underlying mechanisms for phloretin's effects on adipogenesis remain unclear. In this study, we demonstrated that phloretin enhanced the lipid accumulation in porcine primary adipocytes in a time-dependent manner. Furthermore, phloretin increased the utilization of glucose and nonesterified fatty acid, while it decreased the lactate output. Microarray analysis revealed that genes associated with peroxisome proliferator-activated receptor-γ (PPARγ), mitogen-activated protein kinase and insulin signaling pathways were altered in response to phloretin. We further confirmed that phloretin enhanced expression of PPARγ, CAAT enhancer binding protein-α (C/EBPα) and adipose-related genes, such as fatty acids translocase and fatty acid synthase. In addition, phloretin activated the Akt (Thr308) and extracellular signal-regulated kinase, and therefore, inactivated Akt targets protein. Wortmannin effectively blocked the effect of phloretin on Akt activity and the protein levels of PPARγ, C/EBPα and fatty acid binding protein-4 (FABP4/aP2). Oral administration of 5 or 10 mg/kg phloretin to C57BL BKS-DB mice significantly decreased the serum glucose level and improved glucose tolerance. In conclusion, phloretin promotes the adipogenesis of porcine primary preadipocytes through Akt-associated signaling pathway. These findings suggested that phloretin might be able to increase insulin sensitivity and alleviate the metabolic diseases.
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China; Institute of Animal Husbandry & Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China.
authors.forename: Nai-Sheng
authors.initials: NS
authors.lastname: Lu
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Zhu
authors.affiliation: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Rm 8070, Houston, TX 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Min-Qing
authors.initials: MQ
authors.lastname: Du
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Qiu-Ping
authors.initials: QP
authors.lastname: Xie
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Can-Jun
authors.initials: CJ
authors.lastname: Zhu
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Song-Bo
authors.initials: SB
authors.lastname: Wang
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Qian-Yun
authors.initials: QY
authors.lastname: Xi
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: College of Animal Science, South China Agricultural University, Guangzhou 510640, China; National Engineering Research Center For Breeding Swine Industry, Guangzhou, China. Electronic address: qyjiang@scau.edu.cn.
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Jiang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine
chemical_list: D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; D010693:Phloretin
keywords: Akt signaling; Differentiation; FAT/CD36; Glucose; Phloretin; Preadipocytes