Search resultsIsohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor α and γ and reduce insulin resistance
Title
Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor α and γ and reduce insulin resistance
Publication type
Journal Article
Year of Publication
2004
Authors
Journal
Journal of Biological Chemistry
Volume
279
Issue
32
Pagination
33456 - 33462
Date published
2004
ISBN
00219258 (ISSN)
Keywords
2,4 thiazolidinedione derivative, Activation analysis, adipocyte, Adipocytes, Adolescent, Adult, Aged, animal model, animal tissue, Animalia, Animals, apoptosis, article, beer, biochemistry, biosensor, Blood Glucose, body weight, carbohydrate metabolism, cell size, clinical article, clinical trial, controlled clinical trial, controlled study, Cyclopentanes, Diabetes Mellitus, Type 2, Dietary Fats, dose response, double blind procedure, Double-Blind Method, drug effect, drug efficacy, drug mechanism, Drug products, drug structure, experimental diabetes mellitus, fat intake, fatty acid, fatty acid blood level, fatty acid metabolism, Fatty Acids, Fatty Acids, Nonesterified, Female, fibric acid derivative, glucose, glucose blood level, glucose tolerance, Hemoglobin A, Glycosylated, hemoglobin A1c, Homologs, Hops, human, Humans, Humulus, Humulus lupulus, Humulus lupulus extract, insulin dependent diabetes mellitus, insulin resistance, isocohumulone, isohumulone, lipid diet, Lipids, lipoprotein lipase, liver metabolism, male, Mice, Mice, Inbred C57BL, Middle Aged, mouse, mouse strain, natural product, nonhuman, nucleotide sequence, oxidation, Patient treatment, peroxisome proliferator activated receptor alpha, peroxisome proliferator activated receptor gamma, Pilot Projects, pioglitazone, placebo, Placebos, Plant extracts, priority journal, randomized controlled trial, receptor upregulation, Receptors, Receptors, Cytoplasmic and Nuclear, Recombinant Fusion Proteins, RNA, Messenger, Saccharomyces cerevisiae Proteins, Sensors, Thiazolidinediones, Transcription Factors, Transfection, triacylglycerol, triacylglycerol blood level, Triglycerides, unclassified drug, weight gain
Abstract
The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of fibrate drugs and the therapeutic benefits of the thiazolidinedione drugs are due to their activation of PPARα and -γ, respectively. In this study, isohumulones, the bitter compounds derived from hops that are present in beer, were found to activate PPARα and -γ in transient co-transfection studies. Among the three major isohumulone homologs, isohumulone and isocohumulone were found to activate PPARα and -γ. Diabetic KK-Ay mice that were treated with isohumulones (isohumulone and isocohumulone) showed reduced plasma glucose, triglyceride, and free fatty acid levels (65.3, 62.6, and 73.1%, respectively, for isohumulone); similar reductions were found following treatment with the thiazolidinedione drug, pioglitazone. Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10.6% increase versus control group). C57BL/6N mice fed a high fat diet that were treated with isohumulones showed improved glucose tolerance and reduced insulin resistance. Furthermore, these animals showed increased liver fatty acid oxidation and a decrease in size and an increase in apoptosis of their hypertrophic adipocytes. A double-blind, placebo-controlled pilot study for studying the effect of isohumulones on diabetes suggested that isohumulones significantly decreased blood glucose and hemoglobin A1c levels after 8 weeks (by 10.1 and 6.4%, respectively, versus week 0). These results suggest that isohumulones can improve insulin sensitivity in high fat diet-fed mice with insulin resistance and in patients with type 2 diabetes.