PMID- 31917283 OWN - NLM STAT- MEDLINE DCOM- 20210104 LR - 20221207 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 152 DP - 2020 Feb TI - Oral administration of spa-derived green alga improves insulin resistance in overweight subjects: Mechanistic insights from fructose-fed rats. PG - 104633 LID - S1043-6618(19)30824-2 [pii] LID - 10.1016/j.phrs.2020.104633 [doi] AB - Advanced glycation end products (AGEs) and their receptor (RAGE) system evoke inflammatory reactions and insulin resistance in adipocytes. Spa-derived green alga Mucidosphaerium sp. (MS) had anti-inflammatory properties in vitro. We examined here whether and how MS could ameliorate insulin resistance in fructose-rich diet-fed rats, and conducted a randomized, double blind, placebo-controlled trial to investigate the effects of MS on insulin resistance in overweight subjects. Oral administration of MS for 8 weeks significantly decreased random blood glucose, and fasting insulin, oxidative stress levels, and improved homeostasis model assessment of insulin resistance (HOMA-IR) values in fructose-fed rats, which were associated with the reduction of AGEs, RAGE, 8-hydroxy-2'-deoxy-guanosine, NADPH oxidase activity, macrophage and lymphocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, and adipocyte size in the adipose tissues as well as restoration of adiponectin levels. MS decreased the AGE-induced NADPH oxidase activity, ROS generation, MCP-1 and RAGE gene expression, and lipid accumulation in differentiated adipocytes, while it restored the decrease in adiponectin mRNA levels. An anti-oxidant, N-acetylcysteine mimicked the effects of MS on ROS generation, RAGE gene expression, and lipid accumulation. Oral intake of MS for 12 weeks significantly decreased systolic and diastolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, HDL-cholesterol and creatinine in overweight subjects. Baseline-adjusted diastolic blood pressure, fasting plasma glucose, fasting insulin, and HOMA-IR values were significantly lower in MS treatment group than in placebo. Our present findings suggest that MS may improve insulin resistance by blocking the AGE-RAGE-oxidative stress axis in the adipose tissues. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Kaseda, Kuniyoshi AU - Kaseda K AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan; Department of Hospital Administration, Juntendo University School of Medicine, Tokyo, Japan. FAU - Kai, Yuya AU - Kai Y AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Tajima, Masahiro AU - Tajima M AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Suematsu, Mika AU - Suematsu M AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Iwata, Shunsuke AU - Iwata S AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Miyata, Mitsuyoshi AU - Miyata M AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Mifude, Chie K AU - Mifude CK AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Yamashita, Naoki AU - Yamashita N AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Seiryu, Wakana A AU - Seiryu WA AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Fukada, Maki AU - Fukada M AD - Saravio Central Institute, Saravio Cosmetics Ltd., Oita, Japan. FAU - Kobayashi, Hiroyuki AU - Kobayashi H AD - Department of Hospital Administration, Juntendo University School of Medicine, Tokyo, Japan. FAU - Sotokawauchi, Ami AU - Sotokawauchi A AD - Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. FAU - Matsui, Takanori AU - Matsui T AD - Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. Electronic address: matsui_takanori@med.kurume-u.ac.jp. FAU - Yamagishi, Sho-Ichi AU - Yamagishi SI AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. Electronic address: shoichi@med.showa-u.ac.jp. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200107 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Adiponectin) RN - 0 (Chemokine CCL2) RN - 0 (Glycation End Products, Advanced) RN - 0 (Receptor for Advanced Glycation End Products) RN - 30237-26-4 (Fructose) RN - EC 1.6.3.- (NADPH Oxidases) SB - IM MH - 3T3-L1 Cells MH - Adiponectin/metabolism MH - Administration, Oral MH - Adult MH - Animals MH - Asian People MH - Chemokine CCL2/metabolism MH - *Chlorophyta MH - Diet MH - Double-Blind Method MH - Female MH - Fructose MH - Glycation End Products, Advanced/metabolism MH - Hot Springs MH - Humans MH - *Insulin Resistance MH - Male MH - Mice MH - Middle Aged MH - NADPH Oxidases/metabolism MH - Overweight/metabolism/*therapy MH - Rats, Wistar MH - Receptor for Advanced Glycation End Products/metabolism MH - Young Adult OTO - NOTNLM OT - Adipose tissue OT - Advanced glycation end products (AGEs) OT - Inflammation OT - Insulin resistance OT - RAGE COIS- Declaration of Competing Interest Y.K., M.S., S.I., M.M., C.K.M., N.Y., W.S., M.F., M.T., and K.K. were employees of Saravio Cosmetics Ltd. EDAT- 2020/01/10 06:00 MHDA- 2021/01/05 06:00 CRDT- 2020/01/10 06:00 PHST- 2019/05/09 00:00 [received] PHST- 2020/01/02 00:00 [revised] PHST- 2020/01/03 00:00 [accepted] PHST- 2020/01/10 06:00 [pubmed] PHST- 2021/01/05 06:00 [medline] PHST- 2020/01/10 06:00 [entrez] AID - S1043-6618(19)30824-2 [pii] AID - 10.1016/j.phrs.2020.104633 [doi] PST - ppublish SO - Pharmacol Res. 2020 Feb;152:104633. doi: 10.1016/j.phrs.2020.104633. Epub 2020 Jan 7.