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Licochalcone F alleviates glucose tolerance and chronic inflammation in diet-induced obese mice through Akt and p38 MAPK

Bak, Eun-Jung, Choi, Kyung-Chul, Jang, Sungil, Woo, Gye-Hyeong, Yoon, Ho-Geun, Na, Younghwa, Yoo, Yun-Jung, Lee, Youngseok, Jeong, Yangsik, Cha, Jeong-Heon
Clinical nutrition 2016 v.35 pp. 414-421
adipocytes, animal disease models, anti-inflammatory activity, blood, body weight changes, droplets, fatty liver, food intake, gene expression, glucose, glucose tolerance, glycogen, inducible nitric oxide synthase, inflammation, interleukin-1beta, interleukin-6, liver, luciferase, macrophages, messenger RNA, mice, mitogen-activated protein kinase, noninsulin-dependent diabetes mellitus, obesity, reverse transcriptase polymerase chain reaction, signal transduction, transcription factor NF-kappa B, tumor necrosis factor-alpha, white adipose tissue
Licochalcone (lico) F is a novel synthetic retrochalcone. In this study, we investigated the anti-inflammatory effects of lico F in vitro, and its effects on obesity-induced chronic inflammation, glucose intolerance, and fatty liver in vivo.The inhibitory effects of lico F on TNFα-induced inflammation were investigated using NF-κB luciferase reporter assay and RT-PCR. Diet-induced obese mice were treated orally, once per day, with vehicle or lico F (10 mg/kg/day), for 3 weeks, and blood, liver, and adipose tissues were analyzed.Lico F inhibited TNFα-induced NF-κB activation and mRNA expression of TNFα, COX-2, IL-6, IL-1β, and NOS2. In obese mice, lico F administration significantly alleviated glucose tolerance without changes in body weight gain and food intake. Lico F reduced adipocyte size and macrophage infiltration into white adipose tissue and improved hepatic lesions, by decreasing fat droplets and glycogen deposition. The mRNA expression levels of TNFα, MCP-1, and CD68 in white adipose tissue also decreased markedly. Moreover, lico F enhanced Akt signaling, but reduced p38 MAPK signaling in white adipose tissue.Lico F had anti-inflammatory effects and showed beneficial effects on glucose metabolism, which could be partially caused by activation of the Akt signal pathway and obesity-induced chronic inflammation, probably by downregulating p38 signal pathway. Moreover, lico F could be used as a potential novel therapeutic compound against type 2 diabetes and obesity-induced chronic inflammation without the deleterious effects of body weight gain and fatty liver.