scholarly journals Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance

Medicines ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 34
Author(s):  
Jeralyn Franson ◽  
Julianne Grose ◽  
Kaitlyn Larson ◽  
Laura Bridgewater
Keyword(s):  
Weight Gain ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Nutrient Sensing ◽  
Metabolic Effects ◽  
High Fat ◽  
Serine Threonine Kinase ◽  
16S Sequencing ◽  
Triglyceride Accumulation ◽  
Pas Kinase

Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per–Arnt–Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK−/−) protects against triglyceride accumulation, insulin resistance, and weight gain on a high-fat diet; conditions that are associated with dysbiosis of the gut microbiome. Methods: Herein, we report the metabolic effects of the interplay of diet (high fat high sugar, HFHS), genotype (PASK−/−), and microbiome (16S sequencing). Results: Microbiome analysis identified a diet-induced, genotype-independent forked shift, with two discrete clusters of HFHS mice having increased beta and decreased alpha diversity. A “lower” cluster contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres, and was associated with increased weight gain, glucose intolerance, triglyceride accumulation, and decreased claudin-1 expression. Genotypic effects were observed within the clusters, lower cluster PASK−/− mice displayed increased weight gain and decreased triglyceride accumulation, whereas upper PASK−/− were resistant to decreased claudin-1. Conclusions: These results confirm previous reports that PAS kinase deficiency can protect mice against the deleterious effects of diet, and they suggest that microbiome imbalances can override protection. In addition, these results support a healthy diet for beneficial microbiome maintenance and suggest microbial culprits associated with metabolic disease.

scholarly journals Gut Microbiota Regulates the Interplay between Diet and Genetics to Influence Glucose Tolerance †

Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 17
Author(s):  
Jeralyn J. Franson ◽  
Julianne H. Grose ◽  
Kaitlyn Williams Larson ◽  
Laura C. Bridgewater
Keyword(s):  
Weight Gain ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Nutrient Sensing ◽  
Metabolic Effects ◽  
Leaky Gut ◽  
Liver Triglyceride ◽  
High Fat ◽  
Triglyceride Accumulation ◽  
Pas Kinase

Per-arnt-sim (PAS) kinase is a nutrient sensing serine/threonine kinase whose absence protects against triglyceride accumulation, insulin resistance, a decreased metabolic rate and increased weight gain in response to a high fat diet, using phenotypes associated with the gut microbiome. Herein we further explored the metabolic effects of PAS kinase-deficiency(PASK−/−) on a high fat high sugar (HFHS) diet, including contributions from an altered microbiome. PASK−/− mice were not protected from weight gain on the HFHS diet but were resistant to liver triglyceride accumulation. Microbiome analysis of both WT and PASK−/− mice revealed a forked shift with two discrete clusters of HFHS-fed mice emerging, which displayed increased beta and decreased alpha diversity compared with the normal chow diet (NCD). A “lower” cluster associated with both increased weight gain and glucose intolerance contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres. Lower cluster PASK−/− mice also influenced glucose tolerance and Claudin-1 expression, a protein associated with leaky gut. These results suggest PAS kinase-deficiency can protect mice against the deleterious effects of liver triglyceride accumulation, leaky gut and glucose intolerance in response to diet; however, microbiome imbalance can override protection. In addition, these results support a healthy diet and suggest microbial culprits associated with metabolic disease.

scholarly journals Weight Gain, Glucose Tolerance, and the Gut Microbiome of Male C57BL/6J Mice Housed on Corncob or Paper Bedding and Fed Normal or High-Fat Diet

2021 ◽  
Author(s):  
Mohammed R Islam ◽  
Kimberly A Schultz ◽  
Mita Varghese ◽  
Simin H Abrishami ◽  
Jason S Villano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
White Adipose Tissue ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Animal Husbandry ◽  
Normal Diet ◽  
High Fat ◽  
16S Sequencing ◽  
Similar Body

Understanding how differences in animal husbandry practices affect the reproducibility of research results is critical. Wesought to understand how different beddings might influence dietary obesity studies. We compared the effects of paper andcorncob bedding on weight gain, metabolism, and gut microbiome (GM) of mice fed a high-fat diet (HFD) or a normal diet(ND) and evaluated effects on fecal and cecal microbiomes collected from these cohorts after euthanasia. Male C57BL/6J mice at 5 wk age were allowed to acclimate to the facility and the assigned bedding for one week before being placed on HFD or remaining on the ND for 12 wk. Fecal pellets and cecal samples were collected and frozen for batched 16S sequencing. Mice had similar body weight, visceral gonadal white adipose tissue (GWAT), subcutaneous inguinal white adipose tissue (IWAT), liver and spleen weights and metabolic changes regardless of the bedding type. Baseline microbiota differences were detected one week after bedding assignment. After 12 wk, the GM showed significant differences depending on both bedding and diet. The effects of the bedding were not significantly different between endpoint fecal and cecal GM, despite the inherent differences in microbiota in fecal and cecal samples. A correlation was detected between diet and the relative abundance of Bacteroidetes and Verrucomicrobia:Akkermansia. In conclusion, this study demonstrates the importance of considering bedding type when performing dietary experiments.

scholarly journals Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Woo Nam ◽  
Seok Hyun Nam ◽  
Sung Phil Kim ◽  
Carol Levin ◽  
Mendel Friedman
Keyword(s):  
Weight Gain ◽  
High Fat Diet ◽  
Biological Activities ◽  
The Body ◽  
High Fat ◽  
In Vivo Models ◽  
Triglyceride Accumulation ◽  
In Cells

Abstract Background The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice. Methods Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations. Results The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound. Conclusion The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.

scholarly journals Per-Arnt-Sim Kinase (PASK) Deficiency Increases Cellular Respiration on a Standard Diet and Decreases Liver Triglyceride Accumulation on a Western High-Fat High-Sugar Diet

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1990 ◽  
Author(s):  
Jenny Pape ◽  
Colleen Newey ◽  
Haley Burrell ◽  
Audrey Workman ◽  
Katelyn Perry ◽  
...  
Keyword(s):  
The United States ◽  
Cellular Respiration ◽  
Standard Diet ◽  
Male Mice ◽  
Hepatic Triglyceride ◽  
High Fat ◽  
High Sugar ◽  
Triglyceride Accumulation ◽  
Pas Kinase

Diabetes and the related disease metabolic syndrome are epidemic in the United States, in part due to a shift in diet and decrease in physical exercise. PAS kinase is a sensory protein kinase associated with many of the phenotypes of these diseases, including hepatic triglyceride accumulation and metabolic dysregulation in male mice placed on a high-fat diet. Herein we provide the first characterization of the effects of western diet (high-fat high-sugar, HFHS) on Per-Arnt-Sim kinase mice (PASK−/−) and the first characterization of both male and female PASK−/− mice. Soleus muscle from the PASK−/− male mice displayed a 2-fold higher oxidative phosphorylation capacity than wild type (WT) on the normal chow diet. PASK−/− male mice were also resistant to hepatic triglyceride accumulation on the HFHS diet, displaying a 2.7-fold reduction in hepatic triglycerides compared to WT mice on the HFHS diet. These effects on male hepatic triglyceride were further explored through mass spectrometry-based lipidomics. The absence of PAS kinase was found to affect many of the 44 triglycerides analyzed, preventing hepatic triglyceride accumulation in response to the HFHS diet. In contrast, the female mice showed resistance to hepatic triglyceride accumulation on the HFHS diet regardless of genotype, suggesting the effects of PAS kinase may be masked.

scholarly journals Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 393-393
Author(s):  
Moamen Elmassry ◽  
Eunhee Chung ◽  
Abdul Hamood ◽  
Chwan-Li Shen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Alpha Diversity ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Microbiome Composition ◽  
And Function

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

scholarly journals Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Lihong Hao ◽  
Nicholas T. Bello
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
High Fat Diet ◽  
The United States ◽  
Metabolic Effects ◽  
Control Group ◽  
Oral Glucose ◽  
High Fat ◽  
Oral Gavage ◽  
Raspberry Ketone

Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin (Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha (Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln, and increases hepatic Ppara expression.

scholarly journals Estradiol modulates gut microbiota in female ob/ob mice fed a high fat diet

2019 ◽  
Author(s):  
Kalpana D Acharya ◽  
Xing Gao ◽  
Elizabeth P Bless ◽  
Jun Chen ◽  
Marc J Tetel
Keyword(s):  
Weight Gain ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
High Fat ◽  
Diet Induced Obesity ◽  
The Family ◽  
Satiety Hormone ◽  
17Β Estradiol

AbstractEstrogens protect against diet-induced obesity in women and female rodents. In support of these anorectic effects, lack of estrogens in postmenopausal women is associated with weight gain, increasing their risk for cardiovascular diseases and cancer. Estrogens act with leptin, a satiety hormone encoded by the ob gene, to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. In addition to estrogens and leptin, the gut microbiome (gut microbes and their metabolites), is critical in regulating energy metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) control mice fed a high-fat diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes compared to vehicle counterparts. Moreover, both obesity (ob/ob mice) and E2 reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared to vehicle mice. Regarding taxa, E2 treatment was associated with higher abundances of the family S24-7. Leptin was associated with higher abundances of Coriobacteriaceae, Clostridium and Lactobacillus. E2 and leptin had overlapping effects on relative abundances of some taxa, suggesting that interaction of these hormones is important in gut microbial homeostasis. Taken together, these findings suggest that E2 and leptin profoundly alter the gut microbiota of HFD-fed female mice. Understanding the function of E2 and leptin in regulating gut microbiota will allow the development of therapies targeting the gut microbiome for hormone-dependent metabolic disorders in women.

Chronic social stress lessens the metabolic effects induced by a high fat diet

2021 ◽  
Author(s):  
Tanja Jene ◽  
Inigo Ruiz de Azua ◽  
Annika Hasch ◽  
Jennifer Klüpfel ◽  
Julia Deuster ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Negative Consequences ◽  
High Fat ◽  
Glucose Levels ◽  
Metabolic Dysregulation

Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high fat diet (HFD), aggravates the metabolic phenotype, and whether there are particularly sensitive time windows for the negative consequences of HFD exposure. Chronically stressed male mice and controls (CTRL) were kept under (i) SD-conditions, (ii) with HFD commencing post-CSD, or (iii) provided with HFD lasting throughout, and after CSD. Under SD conditions, stress increased glucose levels early post-CSD. Both HFD regimens increased glucose levels in non-stressed mice, but not in stressed mice. Nonetheless, when HFD was provided after CSD, stressed mice did not differ from controls in long-term body weight gain, fat tissue mass and plasma insulin, and leptin levels. In contrast, when HFD was continuously available, stressed mice displayed reduced body weight gain, lowered plasma levels of insulin, and leptin, and reduced white adipose tissue weights as compared to their HFD-treated non-stressed controls. Interestingly, stress-induced adrenal hyperplasia and hypercortisolemia were observed in mice treated with SD and with HFD after CSD, but not in stressed mice exposed to a continuous HFD treatment. The present work demonstrates that CSD can reduce HFD-induced metabolic dysregulation. Hence, HFD during stress may act beneficially, as comfort food, by decreasing stress-induced metabolic demands.

scholarly journals Polymannuronic acid ameliorated obesity and inflammation associated with a high-fat and high-sucrose diet by modulating the gut microbiome in a murine model

2017 ◽  
Vol 117 (9) ◽  
pp. 1332-1342 ◽  
Author(s):  
Fang Liu ◽  
Xiong Wang ◽  
Hongjie Shi ◽  
Yuming Wang ◽  
Changhu Xue ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gut Microbiome ◽  
Body Weight Gain ◽  
High Fat ◽  
Microbial Composition ◽  
The Metabolic Syndrome ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

AbstractPolymannuronic acid (PM), one of numerous alginates isolated from brown seaweeds, is known to possess antioxidant activities. In this study, we examined its potential role in reducing body weight gain and attenuating inflammation induced by a high-fat and high-sucrose diet (HFD) as well as its effect on modulating the gut microbiome in mice. A 30-d PM treatment significantly reduced the diet-induced body weight gain and blood TAG levels (P<0·05) and improved glucose tolerance in male C57BL/6J mice. PM decreased lipopolysaccharides in blood and ameliorated local inflammation in the colon and the epididymal adipose tissue. Compared with low-fat and low-sucrose diet (LFD), HFD significantly reduced the mean number of species-level operational taxonomic units (OTU) per sample as well as species richness (P<0·05) but did not appear to affect other microbial diversity indices. Moreover, compared with LFD, HFD altered the abundance of approximately 23 % of the OTU detected (log10 linear discriminant analysis (LDA) score>2·0). PM also had a profound impact on the microbial composition in the gut microbiome and resulted in a distinct microbiome structure. For example, PM significantly increased the abundance of a probiotic bacterium, Lactobacillus reuteri (log10 LDA score>2·0). Together, our results suggest that PM may exert its immunoregulatory effects by enhancing proliferation of several species with probiotic activities while repressing the abundance of the microbial taxa that harbor potential pathogens. Our findings should facilitate mechanistic studies on PM as a potential bioactive compound to alleviate obesity and the metabolic syndrome.

scholarly journals Infant Weight Gain Trajectories Linked to Oral Microbiome Composition

2017 ◽  
Author(s):  
Sarah J. C. Craig ◽  
Daniel Blankenberg ◽  
Alice Carla Luisa Parodi ◽  
Ian M. Paul ◽  
Leann L. Birch ◽  
...  
Keyword(s):  
Weight Gain ◽  
Gut Microbiome ◽  
Growth Curves ◽  
Later Life ◽  
Child Growth ◽  
Growth Patterns ◽  
Oral Microbiome ◽  
Rapid Weight Gain ◽  
16S Sequencing ◽  
Microbiome Composition

ABSTRACTGut and oral microbiome perturbations have been observed in obese adults and adolescents. Less is known about how weight gain in early childhood is influenced by gut, and particularly oral, microbiomes. Here we analyze the relationships among weight gain and gut and oral microbiomes in 226 two-year-olds who were followed during the first two years of life, as part of a larger study, with weight and length measured at seven time points. We used these data to identify children with rapid weight gain (a strong risk factor for childhood obesity), and to derive growth curves with novel Functional Data Analysis (FDA) techniques. The children’s oral and gut microbiomes were sampled at the end of the two-year period, and surveyed with 16S sequencing. First, we show that growth curves are associated negatively with diversity and positively with Firmicutes-to-Bacteroidetes ratio of the oral microbiome – a relationship that is also observed in children with rapid (vs. non-rapid) weight gain. We also demonstrate an association between the gut microbiome and child growth, but only when considering the effect of diet on the microbiome. Lastly, we identify several bacterial genera that are associated with child growth patterns. These results suggest that by the age of two, the oral microbiome may have already begun to establish patterns often seen in older obese individuals. They also suggest that the gut microbiome, while strongly influenced by diet, at age two does not harbor obesity signatures many researchers identified in later life stages.

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