Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice

Miranda, Cristobal L.; Johnson, Lance A.; Montgolfier, Oriane De; Elias, Valerie; Ullrich, Lea S.; Hay, Joshua J.; Paraiso, Ines L.; Choi, Jaewoo; Reed, Ralph L.; Revel, Johana S.; Kioussi, Chrissa; Bobe, Gerd; Iwaniec, Urszula T.; Turner, Russell T.; Katzenellenbogen, Benita S.; Katzenellenbogen, John A.; Blakemore, Paul R.; Gombart, Adrian F.; Maier, Christoph; Raber, Jacob; Stevens, Jan F.

doi:10.1038/s41598-017-18992-6

Cited by 58 publications

(126 citation statements)

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“…Concentrations of blood glucose and plasma concentrations of TAG, and leptin were determined as described previously, and plasma insulin was determined using a mouse insulin ELISA kit (Alpco Diagnostics, Salem, NH, USA) [52]. The plasma HDL-C concentration was determined using the MaxDiscovery™ HDL-C Cholesterol Assay Kit (Bio Scientific Corporation, Austin, TX, USA).…”

Section: Measurement Of Blood Metabolic Profilesmentioning

confidence: 99%

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Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia

et al. 2020

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A calorie-dense diet is a well-established risk factor for obesity and metabolic syndrome (MetS), whereas the role of the intestinal microbiota (IMB) in the development of diet-induced obesity (DIO) is not completely understood. To test the hypothesis that Swiss Webster (Tac:SW) mice can develop characteristics of DIO and MetS in the absence of the IMB, we fed conventional (CV) and germ-free (GF) male Tac:SW mice either a low-fat diet (LFD; 10% fat derived calories) or a high-fat diet (HFD; 60% fat derived calories) for 10 weeks. The HFD increased feed conversion and body weight in GF mice independent of the increase associated with the microbiota in CV mice. In contrast to CV mice, GF mice did not decrease feed intake on the HFD and possessed heavier fat pads. The HFD caused hyperglycemia, hyperinsulinemia, and impaired glucose absorption in GF mice independent of the increase associated with the microbiota in CV mice. A HFD also elevated plasma LDL-cholesterol and increased hepatic triacylglycerol, free fatty acids, and ceramides in all mice, whereas hypertriglyceridemia and increased hepatic medium and long-chain acylcarnitines were only observed in CV mice. Therefore, GF male Tac:SW mice developed several detrimental effects of obesity and MetS from a high-fat, calorie dense diet.

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Section: Measurement Of Blood Metabolic Profilesmentioning

confidence: 99%

“…GF mice received a higher concentration of glucose to ensure an increase in blood glucose concentrations. Blood taken from the tail vein was sampled using a hand-held glucometer at 0, 15, 30, 60, and 120 min, as described previously [52].…”

Section: Glucose Tolerance Testmentioning

confidence: 99%

Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia

et al. 2020

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“…The same group found that XN and its hydrogenated derivatives α, β-dihydro-xanthohumol (DXN) and tetrahydro-xanthohumol (TXN) improved glucose tolerance as well as cognitive function in mice fed with high fat diet. The study suggested beneficial effects of DXN and TXN in obese mice, fed high fat diet, with metformin associated neuro-metabolic impairments, without risk of liver injury and adverse estrogenic effects [35].…”

Section: Benefits Of Xanthohumol In Hyperlipidaemia Obesity and Typementioning

confidence: 92%

Benefits of Xanthohumol in Hyperlipidaemia, Obesity and Type 2 Diabetes Mellitus: A Review

Rossi¹,

Whyand²,

Caplin³

2019

J Obes Chronic Dis

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Diabetes, obesity, hyperlipidaemia, as well as cardiovascular diseases in general, have become an increasing social and economic problem in developed countries. Hops contain Xanthohumol (XN), a chalcone within a group of prenylated phenols. Used alone, it has recently shown promising results in the management of these individual conditions and we have therefore undertaken a review and assessed the evidence for XN as a food supplement in this setting. Materials and Methods: A PubMed and Cochrane search was performed for the terms: xanthohumol; hyperlipidaemia; obesity; type 2 diabetes mellitus. All relevant articles published over the last 15 years were considered for this review. Results: A total of 39 papers were considered and 18 papers met the criteria for review and these included both in vitro and in vivo (including animal) studies. The studies suggest that XN improves high density lipoprotein (HDL) levels and optimise cholesterol transport, thus having a protective effect against atherosclerosis. Furthermore, XN might exert an anti-obesity effect by decreasing adipogenesis and inducing lipolysis. Finally, XN might also prevent insulin resistance and modulate glucose metabolic pathways. Conclusion: In vitro and in vivo studies (predominantly animal studies) showed promising results for XN in the prevention and treatment of hyperlipidaemia, obesity and T2DM. However, further studies in humans are required to draw more robust conclusions.

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“…Insulin levels in plasma were assessed using enzyme-linked immunosorbent assay (ELISA) kits from EMD Millipore (Billerica, MA) for insulin. The homeostatic model assessment of insulin resistance (HOMA-IR) of the mice was calculated from the simultaneous samples of plasma insulin and glucose as previously described [16].…”

Section: Analyses Of Metabolic Variablesmentioning

confidence: 99%

Influence of Saskatoon Berry and Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice

Huang

Zhao

Xia³

et al. 2020

Preprint

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Abstract Background Type 2 Diabetes (T2D) has become one of most common and harmful chronic diseases worldwide. T2D is characterized as insulin resistant and is often associated with unhealthy dietary habits. The present study assessed the effects of freeze-dried Saskatoon berry powder (SBp) and cyanidin-3-glucoside (C3G, an anthocyanin enriched in SBp) on metabolism, inflammatory markers and gut microbiota in high fat-high sucrose diet (HFHS) diet induced insulin resistant mice. Results Male C57 BL/6J mice received control, HFHS, HFHS + SBp (8.0 g/kg body weight/day) or HFHS + C3G (7.2 mg/kg/day, equal amount of C3G in 8.0 g/kg/day SBp) diet for 11 weeks. HFHS diet significantly increased the levels of glucose, cholesterol, triglycerides, insulin resistance and inflammatory mediators in plasma. The results of 16S rRNA gene sequencing demonstrated that HFHS diet increased the ratio of Bacteroidetes/Firmicutes (B/F) phylum bacteria and an elevated abundance of Muriculaceae family bacteria in the feces of mice. SBp or C3G supplementation attenuated HFHS diet-induced disorders in metabolism and inflammatory markers, and increased B/F ratio and Muriculaceae abundance in mouse gut compared to HFHS diet alone. The abundance of Muriculaceae in the gut microbiota negatively correlated with body weight, glucose, lipids, insulin resistance and inflammatory mediators in mice. The results of functional predication analysis suggest that HFHS diet upregulated the genes of gut bacteria involved in inflammation-related cellular processes, and inhibited bacteria involved in metabolism. SBp and C3G partially neutralized the alterations induced by HFHS diet in gut microbiota implicated in metabolism or inflammation. Conclusion The findings of the present study suggest that SBp is a potential prebiotic food mitigating Western diet-induced disorders in metabolism, inflammation and gut dysbiosis, and C3G possibly contributes to the beneficial effects of SBp.

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Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice

Cited by 58 publications

References 95 publications

Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia

Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia

Benefits of Xanthohumol in Hyperlipidaemia, Obesity and Type 2 Diabetes Mellitus: A Review

Influence of Saskatoon Berry and Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice

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