Tu1848 Chronic Oral Exposure to Ultrafine Particulate Matter Alters the Cecal Microbiota Composition but Not Ileal Permeability in LDLR-Null Male Mice Fed a High Fat Diet

This study aimed to investigate the effect of uridine on obesity, fat accumulation in liver, and gut microbiota composition in high-fat diet-fed mice.

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A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

International Journal of Molecular Sciences ◽

10.3390/ijms22041647 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1647

Author(s):

Brandi Miller ◽

Rabina Mainali ◽

Ravinder Nagpal ◽

Hariom Yadav

Keyword(s):

High Fat Diet ◽

Microbiota Composition ◽

Preventive Strategies ◽

Human Origin ◽

High Fat ◽

Diabetes In Mice ◽

Diabetes Progression ◽

Gut Microbiota Composition

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.

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Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice

Endocrinology ◽

10.1210/en.2013-1587 ◽

2013 ◽

Vol 154 (12) ◽

pp. 4548-4559 ◽

Cited By ~ 43

Author(s):

Mayumi Inoue ◽

Yibin Jiang ◽

Richard H. Barnes ◽

Masakuni Tokunaga ◽

Gabriel Martinez-Santibañez ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Skeletal Muscles ◽

Matrix Protein ◽

Extracellular Matrix Protein ◽

Male Mice ◽

High Fat ◽

Adipose Tissues ◽

Early Stages ◽

Thrombospondin 1

Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression.

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Yeast β-glucan reduces obesity-associated Bilophila abundance and modulates bile acid metabolism in healthy and high-fat diet mouse models

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00226.2021 ◽

2021 ◽

Author(s):

Sik Yu So ◽

Qinglong Wu ◽

Kin Sum Leung ◽

Zuzanna Maria Kundi ◽

Tor C Savidge ◽

...

Keyword(s):

Bile Acid ◽

Gut Microbiota ◽

High Fat Diet ◽

Metabolic Health ◽

Metabolic Phenotype ◽

Bile Acid Metabolism ◽

Microbiota Composition ◽

High Fat ◽

Mrna Accumulation ◽

Gut Microbiota Composition

Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-week dietary supplementation in healthy mice to evaluate effects of different fiber composition (soluble vs particulate Y-BG) and dose (0.1 vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver Cyp7a1 mRNA abundance and bile acid synthesis. These diet-induced responses were notably different when compared to the prebiotic inulin, and included a marked reduction in fecal Bilophila abundance which we demonstrated as translatable to obesity in population-scale American Gut and TwinsUK clinical cohorts. This prompted us to test whether 2% Y-BG maintained metabolic health in mice fed 60% HFD over 13 weeks. Y-BG consistently altered the gut microbiota composition and reduced Bilophila abundance, with trends observed in improvement of metabolic phenotype. Notably, Y-BG improved insulin sensitization and this was associated with enhanced ileal Glpr1r mRNA accumulation and reduced Bilophila abundance. Collectively, our results demonstrate that Y-BG modulates gut microbiota community composition and bile acid signaling, but the dietary regime needs to be optimized to facilitate clinical improvement in metabolic phenotype in an aggressive high-fat diet animal model.

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Hypoglycemic effects of Auricularia auricula polysaccharides on high fat diet and streptozotocin-induced diabetic mice using metabolomics analysis

Food & Function ◽

10.1039/d1fo02022f ◽

2021 ◽

Author(s):

nannan liu ◽

Xuefeng Chen ◽

Juanna Song ◽

Mengyin Chen ◽

Pin Gong ◽

...

Keyword(s):

Diabetes Mellitus ◽

High Fat Diet ◽

Diabetic Mice ◽

Male Mice ◽

High Fat ◽

Auricularia Auricula ◽

Ultrahigh Performance Liquid Chromatography ◽

Metabolomic Approach ◽

Metabolomics Analysis

This study evaluated the hypoglycemic effect of Auricularia auricula polysaccharides (AAPs) on streptozotocin-induced type 2 diabetes mellitus (T2DM) male mice (C57BL/6J) using a metabolomic approach based on ultrahigh-performance liquid chromatography–Q...

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Influence of gender on OVA-induced airway inflammation in C57/B6J mice on a high-fat diet

European Journal of Inflammation ◽

10.1177/2058739218760946 ◽

2018 ◽

Vol 16 ◽

pp. 205873921876094 ◽

Cited By ~ 1

Author(s):

Gang Yu ◽

Lili Zhu ◽

Haiyan Li ◽

Youyou Shao ◽

Lei Chong ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Inflammatory Cells ◽

Normal Weight ◽

Male Mice ◽

High Fat ◽

Low Fat ◽

Control Male ◽

Low Fat Diet ◽

Asthma Group

Overweight/obesity has been suggested as a risk factor for asthma development, and prospective studies have confirmed that high body weight precedes asthma symptoms. However, the nature of the association between overweight/obese status and asthma remains unclear. Animal models of obesity-related asthma are very useful for understanding disease pathophysiology. Although C57/B6J mice are the most widely used animal model for researching obesity-related asthma, gender differences are not always taken into consideration. Therefore, to explore the effect of gender on the development of obesity-related asthma, both female and male C57/B6J mice were used in this study. The mice were fed with a high-fat diet or a low-fat diet as control. Body weight, body length, liver weight, and Lee’s Index were used to evaluate obesity status, and lung histology, lung inflammatory cells infiltration, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were examined for asthma evaluation. We found that the mean body weight of male mice on a high-fat diet gradually increased and was significantly higher than control male mice on a low-fat diet ( P < 0.01), while no significant differences were found between female mice at the end of 12 weeks of feeding. Furthermore, the obese asthma group female and male mice exhibited significantly high inflammatory cells infiltration than normal weight or obese female and male mice ( P < 0.01). However, the obese asthma group presented higher Neu infiltration, Th1 cytokine, and interferon gamma (IFNγ) concentrations in BALF than the asthma group in both the genders ( P < 0.01). In conclusion, both female and male mice are suitable for the obesity-related asthma model, although male mice might be more stable. Besides, obesity-related asthma is not Th2 type asthma.

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Androgen Receptor-Dependent and Independent Atheroprotection by Testosterone in Male Mice

Endocrinology ◽

10.1210/en.2010-0663 ◽

2010 ◽

Vol 151 (11) ◽

pp. 5428-5437 ◽

Cited By ~ 58

Author(s):

Johan Bourghardt ◽

Anna S. K. Wilhelmson ◽

Camilla Alexanderson ◽

Karel De Gendt ◽

Guido Verhoeven ◽

...

Keyword(s):

Androgen Receptor ◽

Apolipoprotein E ◽

High Fat Diet ◽

Atherosclerotic Lesion ◽

Male Mice ◽

Wild Type ◽

High Fat ◽

Lesion Area ◽

Major Pathway

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.

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Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Animals ◽

10.3390/ani11113187 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3187

Author(s):

Eunkuk Park ◽

Chang-Gun Lee ◽

Hyoju Jeon ◽

Hyesoo Jeong ◽

Subin Yeo ◽

...

Keyword(s):

High Fat Diet ◽

Insulin Action ◽

Normal Diet ◽

Male Mice ◽

Impaired Glucose Metabolism ◽

High Fat ◽

Beneficial Effects ◽

Cornus Officinalis ◽

Treatment And Prevention ◽

Obese Male

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

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