Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis

Abstract

Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

BITC and S-Carvone Restrain High-Fat Diet-Induced Obesity and Ameliorate Hepatic Steatosis and Insulin Resistance

“…We have previously shown that blockade of HFD-induced inflammation is a successful strategy to repress weight gain and improve obesity-associated complications (27–30). In this study, we examined the protective activity of BITC and S -carvone against HFD-induced obesity, fatty liver, and insulin resistance.…”

“…Insulin resistance increases gluconeogenesis and decreases blood glucose absorption, leading to glucose intolerance. Many studies have shown that antioxidants are effective in blocking inflammation, increasing insulin sensitivity and improving glucose homeostasis (9, 30, 31). Consistent with these studies, our results show that BITC and S -carvone treatment alleviated insulin resistance and improved glucose intolerance in HFD-fed mice (Fig.…”

Phloretin Promotes Adipogenesis via Mitogen-Activated Protein Kinase Pathways in Mouse Marrow Stromal ST2 Cells

“…These results indicate that phloretin may facilitate adipogenesis in preadipocytes and promote lipolysis in mature adipocytes. Several in vivo studies have shown that the administration of phloretin improves hyperglycemia, insulin resistance [ 20 , 21 ], and obesity [ 20 ] in diabetic rodent models. However, no studies have investigated the effects of phloretin on the commitment of multipotent marrow stromal cells (MSCs) to the adipocytes and its underlying mechanisms, including the contribution of glucose uptake inhibition.…”

Malus toringoides (Rehd.) Hughes Improves Metabolic Syndrome and Liver Injury in High-Fructose-Induced Mice

“…Phloridzin has been reported can improve obesity, insulin resistance and liver lipid degeneration [21]. Phloretin can prevent HFD-induced obesity and improve metabolic homeostasis [22]. Based on the hypoglycemic and hypolipidemic potential of related species in animal models, and diversi ed in vitro and in vivo pharmacological properties of EMT, the current experiment was designed to evaluate the anti-MS effect of M. toringoides leaves against HFruD-induced mice.…”