scholarly journals Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 637
Author(s):  
Priyanka Sharma ◽  
Guojun Wu ◽  
Deeptha Kumaraswamy ◽  
Natalie Burchat ◽  
Hong Ye ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Gut Microbiome ◽  
Lipid Accumulation ◽  
Intestinal Microbiome ◽  
Sexually Dimorphic ◽  
Adipose Tissue Inflammation ◽  
Male Mice ◽  
Female Mice ◽  
Hepatic Lipid Accumulation

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 Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico 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.

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

scholarly journals Sexually Dimorphic Regulation of Gut Microbiota and Body Weight by a Naturally Occurring Flavonoid

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 472-472
Author(s):  
Priyanka Sharma ◽  
Guojun Wu ◽  
Hong Ye ◽  
Yan Y Lam ◽  
Deeptha Kumaraswamy ◽  
...  
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
Intestinal Microbiome ◽  
Sexually Dimorphic ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Naturally Occurring ◽  
Principal Coordinates ◽  
Brown Adipose ◽  
Microbiota Structure

Abstract Objectives 7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that is being actively investigated as a therapeutic modality in the treatment of neurological disorders. A recent study also indicated that oral DHF supplementation protected female but not male mice from diet-induced obesity. However, the mechanisms underlying this sexually-dimorphic effects of DHF were not known. The aim of the work is to investigate the mechanisms underlying sex-specific effects of flavonoid. Methods Age-matched male and female mice were given ad libitum access to high fat-diet and drinking water containing vehicle or DHF for 12 weeks. Body weights, body composition, food, and water intake, were assessed. Immunohistological analysis, immunohistochemistry staining, plasma triglycerides, plasma bile acids, and hepatic lipids were investigated. Fresh fecal samples were collected, genomic DNA was extracted and hypervariable region V4 of the 16S rRNA gene was amplified. Gut microbiota structure was evaluated using alpha diversity indices and beta diversity distance metrices. Principal coordinates analysis (PCoA) was performed using the R “ape” package to visualize differences in gut microbiota structure between treatment groups along principal coordinates that accounted for most of the variations. Results Oral administration of DHF, remodels the intestinal microbiome of female, but not male, prior to divergence in body weight. This is concomitant with increase in brown adipose tissue thermogenesis, mediated by increased expression of UCP1 and Pgc -1α protecting the female mice from diet-induced obesity. Conclusions This study demonstrates sexually-dimorphic effects of a clinically relevant natural compound. Importantly, it points to a role for sex-dependent remodeling of the intestinal microbiome as a mechanism for weight control in females. Thus, our discoveries pave the way for personalized nutrition strategies that account for sex differences in metabolism. Funding Sources NIH.

Swimming’s Prevention of Ovariectomy-Induced Obesity Through Activation of Skeletal-Muscle PPARα

2012 ◽  
Vol 22 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Sunhyo Jeong ◽  
Michung Yoon
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Postmenopausal Women ◽  
Lipid Accumulation ◽  
Mrna Levels ◽  
Adipocyte Size ◽  
Female Mice ◽  
Group A

Ovariectomy leads to weight gain primarily in the form of adipose tissue in rodents. The authors investigated whether swimming improves ovariectomy-induced obesity through activation of peroxisome proliferatoractivated receptor α (PPARα) in the skeletal muscle of female ovariectomized (OVX) mice, an animal model of postmenopausal women. Female mice were randomly divided into 3 groups (n = 8/group): a sedentary sham-operated group, a sedentary OVX group, and a swim-trained OVX group. After mice were subjected to swim training or kept sedentary for 6 wk, the authors studied the effects of swimming on not only bodyweight gain, white adipose tissue (WAT) mass, adipocyte size, and skeletal-muscle lipid accumulation but also the expression of skeletal-muscle PPARα target genes. Sedentary OVX mice had significantly higher body weight and WAT than sedentary sham mice. However, swim training reduced body-weight gain, WAT mass, and adipocyte size of OVX mice. Swim-trained OVX mice had significantly lower levels of serum triglycerides and total cholesterol than sedentary OVX mice. Lipid accumulation in skeletal muscle was also markedly decreased by swimming. Concomitantly, swim training significantly increased mRNA levels of skeletal-muscle PPARα and its target enzymes, as well as uncoupling protein 3 (UCP3) responsible for fattyacid oxidation. These results suggest that swimming can effectively prevent weight gain, adiposity, adipocyte hypertrophy, and lipid disorders caused by ovariectomy, in part through the activation of PPARα and UCP3, in the skeletal muscle of female mice and may contribute to the alleviation of metabolic syndrome, including obesity, hyperlipidemia, and Type 2 diabetes in postmenopausal women.

Vitamin D Deficiency Attenuates High-Fat Diet-Induced Hyperinsulinemia and Hepatic Lipid Accumulation in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 2103-2113 ◽  
Author(s):  
Xiao-Jing Liu ◽  
Bi-Wei Wang ◽  
Cheng Zhang ◽  
Mi-Zhen Xia ◽  
Yuan-Hua Chen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Male Mice ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Consumption of the edible sea urchin Mesocentrotus nudus attenuates body weight gain and hepatic lipid accumulation in mice

2018 ◽  
Vol 47 ◽  
pp. 40-47 ◽  
Author(s):  
Ryoko Yamamoto ◽  
Hisanori Minami ◽  
Hiromi Matsusaki ◽  
Mami Sakashita ◽  
Naoki Morita ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Sea Urchin ◽  
Lipid Accumulation ◽  
Body Weight Gain ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Mesocentrotus Nudus

scholarly journals Luteolin Improves Insulin Resistance in Postmenopausal Obese Mice by Altering Macrophage Polarization (FS12-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yunjung Baek ◽  
Mi Nam Lee ◽  
Dayong Wu ◽  
Munkyong Pae
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Ovarian Function ◽  
Body Weight Gain ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Ovariectomized Mice

Abstract Objectives Previously, we showed that loss of ovarian function in mice fed high-fat diet exacerbated insulin resistance and adipose tissue inflammation. In the current study, we tested whether consumption of luteolin, an anti-inflammatory flavonoid, could mitigate adipose tissue inflammation and insulin resistance in obese ovariectomized mice. Methods Nine-week-old ovariectomized C57BL/6 mice were fed a low-fat diet (LFD), high-fat diet (HFD), or HFD supplemented with 0.005% luteolin (HFD + L) for 16 weeks. The anti-inflammatory drug salicylate was used as a positive control. Fasting blood glucose, insulin, and insulin resistance index HOMA-IR were measured every 4 weeks. Adipose tissue and spleen were characterized for tissue inflammation by real-time PCR and immune cell populations by flow cytometry after 16 weeks of feeding. Results HFD resulted in more body weight gain than LFD in ovariectomized mice and supplementing HFD with 0.005% luteolin did not affect the body weight gain. In addition, HFD elicited a significant elevation in fat mass, which were comparable between HFD and HFD + L groups. However, luteolin supplementation resulted in a significant decrease in CD11c+ macrophages in gonadal adipose tissue, as well as a trend of decrease in macrophage infiltration. Luteolin supplementation also significantly decreased mRNA expression of inflammatory and M1 markers MCP-1, CD11c, TNF-a, and IL-6, while maintaining expression of M2 marker MGL1. We further found that luteolin treatment protected mice from insulin resistance induced by HFD consumption; this improved insulin resistance was correlated with reductions in CD11c+ adipose tissue macrophages. Conclusions Our findings indicate that dietary luteolin supplementation attenuates adipose tissue inflammation and insulin resistance found in mice with loss of ovarian function coupled with a HFD intake, and this effect may be partly mediated through suppressing M1-like polarization of macrophages in adipose tissue. These results have clinical implication in implementing dietary intervention for prevention of metabolic syndrome associated with postmenopause and obesity. Funding Sources Supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2018R1A1A1A05078886).

scholarly journals Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes

2019 ◽  
Vol 216 (7) ◽  
pp. 1542-1560 ◽  
Author(s):  
Hemraj B. Dodiya ◽  
Thomas Kuntz ◽  
Shabana M. Shaik ◽  
Caroline Baufeld ◽  
Jeffrey Leibowitz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Male Mice ◽  
Female Mice ◽  
Antibiotic Cocktail ◽  
Specific Effects ◽  
Plaque Pathology ◽  
Microglial Morphology

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE/presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the “M0” homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

scholarly journals Administration of Saccharin to Neonatal Mice Influences Body Composition of Adult Males and Reduces Body Weight of Females

Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1313-1326 ◽  
Author(s):  
Sebastian D. Parlee ◽  
Becky R. Simon ◽  
Erica L. Scheller ◽  
Emilyn U. Alejandro ◽  
Brian S. Learman ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Bone Mass ◽  
Composition Analysis ◽  
Male Body ◽  
Adult Males ◽  
Male Mice ◽  
Female Mice ◽  
Trabecular Bone Mass ◽  
High Concentrations

Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice.

scholarly journals Deletion of Serum Amyloid A3 Improves High Fat High Sucrose Diet-Induced Adipose Tissue Inflammation and Hyperlipidemia in Female Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e108564 ◽  
Author(s):  
Laura J. den Hartigh ◽  
Shari Wang ◽  
Leela Goodspeed ◽  
Yilei Ding ◽  
Michelle Averill ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Serum Amyloid ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Female Mice ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose
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