Ingredient in hops to treat learning and memory impairments and metabolic changes associated with a high-fat diet
Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and type 2 diabetes. MetS is associated with enhanced risk to develop age-related cognitive impairments and and dementia. Diets high in saturated fat induce inflammation that contributes to the development of MetS. Obesity and consumption of a high-fat diet can impair cognitive function in humans and animal models. In humans, risk factors for developing age-related cognitive decline and dementia include consumption of a high-fat diet, obesity, insulin resistance, type-2 diabetes.
The principal flavonoid found in hops (Humulus lupulus) has anti-obesity effects in the rodent models. However, the use of XN in dietary supplements raises some concerns, as one of its metabolites, is a potent phytoestrogen. Phytoestrogens carry the risk of adverse effects of estrogens. In this study, we used XN along with XN analogues that cannot be converted into phytoestrogens and determined whether they are able to treat MetS and cognitive impairment associated with obesity. Along with a HFD, we administered XN and two XN analogues that cannot be converted into phytoestrogens orally to young adult wild-type mice for 14 weeks. Cognitive impairments induced by a high-fat diet include impairments in spatial navigation, which in turn requires the ability to generate and recall a spatial map. Spatial navigation is the ability to explore the environment to locate a specific location previously visited using cues in the environment (A). Spatial navigation is impaired as part of age-related cognitive decline and especially in dementia.
Mice treated with XN and XN analogues that cannot be converted into phytoestrogens showed improvements of impaired glucose tolerance and decreased plasma insulin and leptin levels. Mice treated with either of these three compounds showed improved spatial learning as compared to mice only receiving the high-fat diet. The mice treated with either of these three compounds showed spatial memory, which was not seen in mice only receiving the high-fat diet (B-D). Thus, our results demonstrate the potential to prevent or treat the cognitive injury and metabolic alterations associated with a high-fat diet. HFD-induced obesity without risk of estrogenic adverse effects.
Jacob Raber, Jan Frederik Stevens
Oregon Health & Science University, USA
Linus Pauling Institute, Oregon State University, USA
PublicationNon-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice.
Cristobal L. Miranda, Lance A. Johnson, Oriane de Montgolfier, Valerie D. Elias, Lea S. Ullrich, Joshua J. Hay, Ines L. Paraiso, Jaewoo Choi, Ralph L. Reed, Johana S. Revel, Chrissa Kioussi, Gerd Bobe, Urszula T. Iwaniec, Russell T. Turner, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Paul R. Blakemore, Adrian F. Gombart, Claudia S. Maier, Jacob Raber & Jan F. Stevens
Sci Rep. 2018 Jan 12
|Can glucose or fructose consumption impair memory? The intake of simple sugars in the human diet has risen in the last decades, especially due to the elevated consumption of sugar-sweetened beverages. This increase in simple sugar consumption…|
|Cyagen Biosciences – Helping you choose the right… While many animal models are available “ off the shelf ” through various repositories and collaborations, generation of novel animal models has allowed for more effective studies, not limited by…|
|Leptin can contribute to evaluate cardiometabolic… Obesity is a major risk factor for the development of cardiometabolic complications and it is proportional to the degree of obesity and, more specifically, the accumulation of visceral fat. The…|
|Suvorexant, a dual orexin receptor antagonist, may… Glucose is the predominant metabolic fuel for the brain. Thus, the mechanism of glucose regulation is crucial to survival. Insulin is the main glucose regulatory hormone among redundant glucose regulatory…|
|Not frozen in time: the past matters to the… Insulin is a hormone which regulates how your food fuels your body. The food you eat is digested and converted into glucose, which then travels through your blood to reach…|
|Early treatment with basal insulin glargine in… The inability to control blood glucose levels can result in many negative health outcomes including eye, kidney, cardiovascular (heart) and foot disease, and early death. Persons with type 2 diabetes…|