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.

Pharmacokinetics of reduced iso-α-acids in volunteers following clear bottled beer consumption

“…These preliminary IAA pharmacokinetic studies demonstrated that IAA compounds can be detected and suggests that the structurally similar reduced IAA may also be able to be targeted. Furthermore, there have been toxicity [19] and pharmacokinetic studies investigating reduced IAA, particularly RIAA and TIAA, due to their possible medicinal properties such as weight loss, antidiabetic, anti-carcinogenic and anti-inflammatory [7,8,[20][21][22][23]. Of these, two studies detected RIAA and TIAA in New Zealand white rabbits [7], and one measured RIAA in humans [8], confirming those reduced IAA groups examined were indeed bioavailable.…”

“…As a result of a study performed where osteoarthritis, rheumatoid arthritis and fibromyalgia patients were prescribed a combination of reduced-IAA and other anti-inflammatory substances [20,23], there have been some supplementary medicines produced that contain RIAA and TIAA [34]. The particular doses of each are not described only that up to 225-370 mg of total reduced IAA content are in each tablet.…”

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

“…Total RNA from tissues was prepared using the TriPure reagent (Roche) as described (14,17). Quantization and integrity analysis of total RNA was performed as previously described (17).…”

Effects of eplerenone on the activation of matrix metalloproteinase-2 stimulated by high glucose and interleukin-1β in human cardiac fibroblasts

“…A previous study found that HG altered the level of MMPs and cytokines in fibroblasts (Westermann et al, 2007). Furthermore, increased pro-inflammatory cytokines have been found in diabetic animal models and diabetic patients (Ersoy et al, 2004;Everard et al, 2012). Moreover, interleukin-1b (IL-1b) and tumor necrosis factor-α were shown to increase the expression and activity of MMP-2 and MMP-9 in cardiac fibroblasts (Siwik et al, 2000).…”