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.