Oral Administration of Spa-derived Green Alga Improves Insulin Resistance in Overweight Subjects: Mechanistic Insights from Fructose-fed Rats.

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.