Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome
7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have n...
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doaj-dd2ed7c4bf2448aeb8257eb0715536cb2021-02-17T00:03:15ZengMDPI AGNutrients2072-66432021-02-011363763710.3390/nu13020637Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut MicrobiomePriyanka Sharma0Guojun Wu1Deeptha Kumaraswamy2Natalie Burchat3Hong Ye4Yongjia Gong5Liping Zhao6Yan Y. Lam7Harini Sampath8Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USACenter for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USARutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USARutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USARutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USACenter for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USACenter for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USACenter for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USARutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, New Brunswick, NJ 08901, USA7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly <i>Desulfovibrionaceae</i>, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and <i>in silico</i> analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.https://www.mdpi.com/2072-6643/13/2/637metabolic syndromeintestinal microbiomedysbiosispolyphenolssex differences |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Priyanka Sharma Guojun Wu Deeptha Kumaraswamy Natalie Burchat Hong Ye Yongjia Gong Liping Zhao Yan Y. Lam Harini Sampath |
spellingShingle |
Priyanka Sharma Guojun Wu Deeptha Kumaraswamy Natalie Burchat Hong Ye Yongjia Gong Liping Zhao Yan Y. Lam Harini Sampath Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome Nutrients metabolic syndrome intestinal microbiome dysbiosis polyphenols sex differences |
author_facet |
Priyanka Sharma Guojun Wu Deeptha Kumaraswamy Natalie Burchat Hong Ye Yongjia Gong Liping Zhao Yan Y. Lam Harini Sampath |
author_sort |
Priyanka Sharma |
title |
Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome |
title_short |
Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome |
title_full |
Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome |
title_fullStr |
Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome |
title_full_unstemmed |
Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome |
title_sort |
sex-dependent effects of 7,8-dihydroxyflavone on metabolic health are associated with alterations in the host gut microbiome |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2021-02-01 |
description |
7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly <i>Desulfovibrionaceae</i>, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and <i>in silico</i> analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies. |
topic |
metabolic syndrome intestinal microbiome dysbiosis polyphenols sex differences |
url |
https://www.mdpi.com/2072-6643/13/2/637 |
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