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3-OH Phloretin Inhibits High-Fat Diet-Induced Obesity and Obesity-Induced Inflammation by Reducing Macrophage Infiltration into White Adipose Tissue.

Abstract
Phloretin and its glycoside phlorizin have been reported to prevent obesity induced by high-fat diet (HFD), but the effect of 3-OH phloretin, a catechol metabolite of phloretin, has not been investigated. In this study, we investigated the anti-obesity effects of phloretin and 3-OH phloretin in HFD-fed mice. The body weight gain induced by HFD was more inhibited by administration of 3-OH phloretin than by phloretin. The increases in fat mass, white adipose tissue (WAT) weight, adipocyte size, and lipid accumulation by HFD were also remarkably inhibited by 3-OH phloretin and, to a lesser extent, by phloretin. The HFD-induced upregulation of chemokines and pro-inflammatory cytokines was suppressed by 3-OH phloretin, preventing M1 macrophages from infiltrating into WAT and thereby reducing WAT inflammation. 3-OH phloretin also showed a more potent effect than phloretin on suppressing the expression of adipogenesis regulator genes, such as PPARγ2, C/EBPα, FAS, and CD36. Fasting blood glucose and insulin levels increased by HFD were diminished by the administration of 3-OH phloretin, suggesting that 3-OH phloretin may alleviate obesity-induced insulin resistance. These findings suggested that 3-OH phloretin has the potential to be a natural bioactive compound that can be used in the prevention or treatment of obesity and insulin resistance.
AuthorsSu-Min Woo, Ngoc Anh Nguyen, Jeong-Eun Seon, Jin Jang, Su-Min Yee, Ngoc Tan Cao, Harim Choi, Chul-Ho Yun, Hyung-Sik Kang
JournalMolecules (Basel, Switzerland) (Molecules) Vol. 28 Issue 4 (Feb 15 2023) ISSN: 1420-3049 [Electronic] Switzerland
PMID36838843 (Publication Type: Journal Article)
Chemical References
  • Phloretin
Topics
  • Animals
  • Mice
  • Insulin Resistance
  • Diet, High-Fat
  • Phloretin (pharmacology)
  • Obesity (metabolism)
  • Adipose Tissue, White (metabolism)
  • Inflammation (metabolism)
  • Macrophages
  • Adipose Tissue (metabolism)
  • Mice, Inbred C57BL

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