Beneficial effects of eicosapentaenoic acid on the metabolic profile of obese female mice entails upregulation of HEPEs and increased abundance of enteric Akkermansia Muciniphila

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

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Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones

Endocrinology ◽

10.1210/en.2006-0311 ◽

2006 ◽

Vol 147 (12) ◽

pp. 5826-5834 ◽

Cited By ~ 95

Author(s):

Shoshana Yakar ◽

Nomeli P. Nunez ◽

Patricia Pennisi ◽

Pnina Brodt ◽

Hui Sun ◽

...

Keyword(s):

Insulin Resistance ◽

Tumor Growth ◽

Glucose Intolerance ◽

Tumor Development ◽

Tumor Growth Rate ◽

Obese Mice ◽

Female Mice ◽

Diet Induced Obesity ◽

Body Adiposity ◽

Obese Female

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

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Effects of aerobic exercise training on obese female mice: metabolic and autonomic evaluation

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1109.1 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Michelle Sartori ◽

Leandro Eziquiel Souza ◽

Pamella Ramona Souza ◽

Fernando Santos ◽

Kátia De Angelis ◽

...

Keyword(s):

Exercise Training ◽

Aerobic Exercise ◽

Aerobic Exercise Training ◽

Female Mice ◽

Obese Female

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Faculty Opinions recommendation of Mineralocorticoid and estrogen receptors in endothelial cells coordinately regulate microvascular function in obese female mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.740050186.793586586 ◽

2021 ◽

Author(s):

Alan Parrish

Keyword(s):

Endothelial Cells ◽

Estrogen Receptors ◽

Microvascular Function ◽

Female Mice ◽

Obese Female

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Abstract P295: Endothelial Sodium Channel Activation Promotes Cardiac Stiffness in Obese Female Mice

Hypertension ◽

10.1161/hyp.68.suppl_1.p295 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Javad Habibi ◽

Annayya R Aroor ◽

Lixin Ma ◽

Guanghong Jia ◽

Adam Whaley-Connell ◽

...

Keyword(s):

Sodium Channel ◽

Low Dose ◽

Interstitial Fibrosis ◽

Diastolic Heart Failure ◽

The United States ◽

High Fat ◽

Female Mice ◽

Obese Female ◽

High Fructose ◽

Endothelial Stiffness

Cardiac diastolic dysfunction (DD) and diastolic heart failure is increasing in concert with obesity and aging population in the United States. In obese and diabetic women, DD is more common than in their male counterparts. This disproportionate increase in DD in obese females may partly explain their loss of sex-related cardiovascular (CV) disease protection. Recent studies have suggested a role for endothelial sodium channel (ENaC) activation in promotion of endothelial stiffness and suppression of flow- (nitric oxide) mediated vasodilation. Moreover, increased mineralocorticoid receptor (MR) activation mediated endothelial stiffness is promoted, in part, by ENaC activation. In this regard, we have recently reported increased plasma aldosterone levels, aortic and cardiac stiffness, and cardiac and vascular MR expression in female mice fed a high fat and high fructose diet (western diet [WD]). This increase in CV stiffness was prevented by very low dose MR antagonism. Accordingly, we hypothesized that inhibition of MR-mediated ENaC activation by using a very low dose of the ENaC inhibitor, amiloride would prevent cardiac stiffening (DD) in WD-fed female mice. Four week old C57BL6/J mice were fed a WD containing high fat (46%), sucrose (17.5%), and high fructose corn syrup (17.5%) with or without a very low dose of amiloride (1mg/kg/day) for 16 weeks. Amiloride significantly attenuated WD-induced impairment of cardiac relaxation in vivo as measured by high resolution magnetic resonance imaging (MRI) as well as cardiac interstitial fibrosis as measured by immunohistochemistry by picrosirius red staining. Moreover, amiloride prevented the development of DD in obese female mice without having effects on blood pressure. These observations support a role for ENaC activation in diet-induced cardiac stiffening (DD) in obese females.

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Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

Microorganisms ◽

10.3390/microorganisms8091413 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1413

Author(s):

Meng Yang ◽

Shambhunath Bose ◽

Sookyoung Lim ◽

JaeGu Seo ◽

JooHyun Shin ◽

...

Keyword(s):

Metabolic Disorders ◽

Intestinal Inflammation ◽

Body Weight Gain ◽

Liver Steatosis ◽

Caloric Intake ◽

Hepatic Function ◽

Low Grade ◽

Mice Model ◽

Akkermansia Muciniphila ◽

Beneficial Effects

The identification of new probiotics with anti-obesity properties has attracted considerable interest. In the present study, the anti-obesity activities of Akkermansia muciniphila (A. muciniphila) strains isolated from human stool samples and their relationship with the gut microbiota were evaluated using a high fat-diet (HFD)-fed mice model. Three strains of A. muciniphila were chosen from 27 isolates selected based on their anti-lipogenic activity in 3T3-L1 cells. The anti-lipogenic, anti-adipogenic and anti-obesity properties of these three strains were evaluated further in HFD-induced obese mice. The animals were administered these strains six times per week for 12 weeks. The treatment improved the HFD-induced metabolic disorders in mice in terms of the prevention of body weight gain, caloric intake and reduction in the weights of the major adipose tissues and total fat. In addition, it improved glucose homeostasis and insulin sensitivity. These effects were also associated with the inhibition of low-grade intestinal inflammation and restoration of damaged gut integrity, prevention of liver steatosis and improvement of hepatic function. These results revealed a difference in the distribution pattern of the gut microbial communities between groups. Therefore, the gut microbial population modulation, at least in part, might contribute to the beneficial impact of the selected A. muciniphila strains against metabolic disorders.

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Overexpression of UBQLN1 reduces neuropathology in the P497S UBQLN2 mouse model of ALS/FTD

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01039-9 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Shaoteng Wang ◽

Micaela Tatman ◽

Mervyn J. Monteiro

Keyword(s):

Mouse Model ◽

Neuronal Loss ◽

Body Weight Loss ◽

Missense Mutations ◽

Homologous Proteins ◽

Female Mice ◽

Beneficial Effects ◽

Therapeutic Benefits ◽

Gender Specific ◽

Lateral Sclerosis

Abstract Missense mutations in UBQLN2 cause X-linked dominant inheritance of amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). UBQLN2 belongs to a family of four highly homologous proteins expressed in humans that play diverse roles in maintaining proteostasis, but whether one isoform can substitute for another is not known. Here, we tested whether overexpression of UBQLN1 can alleviate disease in the P497S UBQLN2 mouse model of ALS/FTD by crossing transgenic (Tg) mouse lines expressing the two proteins and characterizing the resulting genotypes using a battery of pathologic and behavioral tests. The pathologic findings revealed UBQLN1 overexpression dramatically reduced the burden of UBQLN2 inclusions, neuronal loss and disturbances in proteostasis in double Tg mice compared to single P497S Tg mice. The beneficial effects of UBQLN1 overexpression were primarily confirmed by behavioral improvements seen in rotarod performance and grip strength in male, but not female mice. Paradoxically, although UBQLN1 overexpression reduced pathologic signatures of disease in P497S Tg mice, female mice had larger percentage of body weight loss than males, and this correlated with a corresponding lack of behavioral improvements in the females. These findings lead us to speculate that methods to upregulate UBQLN1 expression may reduce pathogenicity caused by UBQLN2 mutations, but may also lead to gender-specific outcomes that will have to be carefully weighed with the therapeutic benefits of UBQLN1 upregulation.

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