PMID- 28197827 OWN - NLM STAT- MEDLINE DCOM- 20180301 LR - 20181113 IS - 1550-7416 (Electronic) IS - 1550-7416 (Linking) VI - 19 IP - 3 DP - 2017 May TI - Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis. PG - 797-805 LID - 10.1208/s12248-017-0053-0 [doi] AB - 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-gamma 2 (Ppargamma2), 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. FAU - Alsanea, Sary AU - Alsanea S AD - Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, 30602, USA. FAU - Gao, Mingming AU - Gao M AD - Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, 30602, USA. FAU - Liu, Dexi AU - Liu D AD - Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, 30602, USA. dliu@uga.edu. LA - eng GR - R01 HL098295/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170214 PL - United States TA - AAPS J JT - The AAPS journal JID - 101223209 RN - 0 (Antioxidants) RN - 0 (Lipids) RN - S5J5OE47MK (Phloretin) SB - IM MH - Adipose Tissue, White/drug effects MH - Adiposity/drug effects MH - Animals MH - Antioxidants/pharmacology/*therapeutic use MH - Diet, High-Fat/adverse effects MH - Drug Evaluation, Preclinical MH - Fatty Liver/etiology/*prevention & control MH - Hyperinsulinism/etiology/prevention & control MH - Inflammation/prevention & control MH - Insulin Resistance MH - Lipids/blood MH - Male MH - Metabolism/*drug effects MH - Mice, Inbred C57BL MH - Obesity/etiology/*prevention & control MH - Phloretin/pharmacology/*therapeutic use MH - Random Allocation OTO - NOTNLM OT - antioxidant OT - inflammation OT - insulin resistance OT - obesity OT - phloretin EDAT- 2017/02/16 06:00 MHDA- 2018/03/02 06:00 CRDT- 2017/02/16 06:00 PHST- 2016/12/22 00:00 [received] PHST- 2017/01/31 00:00 [accepted] PHST- 2017/02/16 06:00 [pubmed] PHST- 2018/03/02 06:00 [medline] PHST- 2017/02/16 06:00 [entrez] AID - 10.1208/s12248-017-0053-0 [pii] AID - 10.1208/s12248-017-0053-0 [doi] PST - ppublish SO - AAPS J. 2017 May;19(3):797-805. doi: 10.1208/s12248-017-0053-0. Epub 2017 Feb 14.