title: Tetrahydro iso-alpha acids from hops improve glucose homeostasis and reduce body weight gain and metabolic endotoxemia in high-fat diet-fed mice.
abstract: Obesity and related metabolic disorders such as insulin resistance and type 2 diabetes are associated with a low-grade inflammatory state possibly through changes in gut microbiota composition and the development of higher plasma lipopolysaccharide (LPS) levels, i.e. metabolic endotoxemia. Various phytochemical compounds have been investigated as potential tools to regulate these metabolic features. Humulus lupulus L. (hops) contains several classes of compounds with anti-inflammatory potential. Recent evidence suggests that hops-derived compounds positively impact adipocyte metabolism and glucose tolerance in obese and diabetic rodents via undefined mechanisms. In this study, we found that administration of tetrahydro iso-alpha acids (termed META060) to high-fat diet (HFD)-fed obese and diabetic mice for 8 weeks reduced body weight gain, the development of fat mass, glucose intolerance, and fasted hyperinsulinemia, and normalized insulin sensitivity markers. This was associated with reduced portal plasma LPS levels, gut permeability, and higher intestinal tight junction proteins Zonula occludens-1 and occludin. Moreover, META060 treatment increased the plasma level of the anti-inflammatory cytokine interleukin-10 and decreased the plasma level of the pro-inflammatory cytokine granulocyte colony-stimulating factor. In conclusion, this research allows us to decipher a novel mechanism contributing to the positive effects of META060 treatment, and supports the need to investigate such compounds in obese and type 2 diabetic patients.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium.
authors.forename: Amandine
authors.initials: A
authors.lastname: Everard
authors.forename: Lucie
authors.initials: L
authors.lastname: Geurts
authors.forename: Marie
authors.initials: M
authors.lastname: Van Roye
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D059305:Diet, High-Fat; D019446:Endotoxemia / Q000188:drug therapy*; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D027582:Humulus / Q000737:chemistry*; D006946:Hyperinsulinism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein
chemical_list: D003517:Cyclopentanes; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; D010936:Plant Extracts; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase; D005947:Glucose