High-Fat Diet Alters the Intestinal Microbiota in Streptozotocin-Induced Type 2 Diabetic Mice

Intestinal microbiota is closely associated with various metabolic diseases such as type 2 diabetes (T2D), and microbiota is definitely affected by diet. However, more work is required to gain detailed information about gut metagenome and their associated impact with diet in T2D patients. We used a streptozotocin-high-fat diet (HFD) to induce a T2D mouse model and investigated the effect of standard chow diet and HFD on the composition and function of gut microbiota. We found that a HFD could worsen the diabetes status compared with a standard diet. 16S rRNA gene sequencing revealed that a HFD caused a large disturbance to the microbial structure and was linked to an increased ratio of Firmicutes to Bacteroidetes. A HFD increased the bacteria of the Ruminococcaceae and Erysipelotrichaceae family and decreased the bacteria of S24-7 and Rikenellaceae. Meanwhile, a HFD decreased the abundance of Parabacteroides distasonis and Eubacterium dolichum, both of which have previously been reported to alleviate obesity and metabolic dysfunctions. Moreover, PICRUSt-predicted KEGG pathways related to membrane transport, lipid metabolism, and xenobiotics biodegradation and metabolism were significantly elevated in HFD-fed T2D mice. Our results provide insights into dietary and nutritional approaches for improving host metabolism and ameliorating T2D.

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Acupuncture Regulating Gut Microbiota in Abdominal Obese Rats Induced by High-Fat Diet

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/4958294 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Haiying Wang ◽

Qiang Wang ◽

Cuimei Liang ◽

Mingxing Su ◽

Xin Wang ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

High Fat Diet ◽

16S Rrna Gene Sequencing ◽

The Body ◽

Chow Diet ◽

Rrna Gene ◽

Sprague Dawley ◽

High Fat ◽

Obese Rats

Objective. To investigate the effects of acupuncture on metabolic health and gut microbiota dysbiosis in diet-induced abdominal obese model. Materials and Methods. Male Sprague-Dawley rats were randomly distributed into normal chow diet (NCD) group and high-fat diet (HFD) group. After 12 weeks of HFD feeding, an abdominal obese rat model was established. The abdominal obese rats were further assigned to acupuncture group (n=7) and nontreated HFD group (n=7). Acupuncture was applied to bilateral GB 26 of rats for 8 weeks. Subsequently, the body weight, waist circumference (WC), visceral fat mass, and liver weight were measured weekly in all rats. Metabolic parameters such as total cholesterol, triglyceride, alanine aminotransferase, aspartate transaminase, and blood glucose were measured by an automatic biochemical analyzer. The serum levels of insulin (INS) were determined using Rat INS ELISA Kit. Analysis of gut microbiota was carried out by 16S rRNA gene sequencing. Results. Acupuncture decreased the body weight, WC, and visceral adipose tissues of HFD-induced abdominal obese rats. In addition, insulin sensitivity, glucose homeostasis, and lipid metabolism were improved by this treatment. Furthermore, electroacupuncture effectively modified the composition of gut microbiota, mainly via decreasing Firmicutes/Bacteroidetes ratio and increasing Prevotella_9 abundance. Conclusions. Electroacupuncture can ameliorate abdominal obesity and prevent metabolic disorders in HFD-induced abdominal obese rats, via the modulation of gut microbiota.

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Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.011840 ◽

2020 ◽

Vol 295 (31) ◽

pp. 10842-10856 ◽

Cited By ~ 1

Author(s):

Wen Liu ◽

Ye Yin ◽

Meijing Wang ◽

Ting Fan ◽

Yuyu Zhu ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Metabolic Disorders ◽

Metabolic Diseases ◽

Low Grade ◽

High Fat ◽

Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

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A pilot of the feasibility and usefulness of an aged obese model for use in stroke research

Wellcome Open Research ◽

10.12688/wellcomeopenres.16592.1 ◽

2021 ◽

Vol 6 ◽

pp. 104

Author(s):

Annastazia E. Learoyd ◽

Ryan Calmus ◽

Chelsea N. Cunningham ◽

Tim J. England ◽

Tracy D. Farr ◽

...

Keyword(s):

High Fat Diet ◽

Artery Occlusion ◽

Standard Diet ◽

High Fat ◽

Stroke Research ◽

Obese Rats ◽

Develop Type ◽

Cerebral Artery Occlusion ◽

Diet Model

Background: Animal models of stroke have been criticised as having poor predictive validity, lacking risk factors prevalent in an aging population. This pilot study examined the development of comorbidities in a combined aged and high-fat diet model, and then examined the feasibility of modelling stroke in such rats. Methods: Twelve-month old male Wistar-Han rats (n=15) were fed a 60% fat diet for 8 months during which monthly serial blood samples were taken to assess the development of metabolic syndrome and pro-inflammatory markers. Following this, to pilot the suitability of these rats for undergoing surgical models of stroke, they underwent 30min of middle cerebral artery occlusion (MCAO) alongside younger controls fed a standard diet (n=10). Survival, weight and functional outcome were monitored, and blood vessels and tissues collected for analysis. Results: A high fat diet in aged rats led to substantial obesity. These rats did not develop type 2 diabetes or hypertension. There was thickening of the thoracic arterial wall and vacuole formation in the liver; but of the cytokines examined changes were not seen. MCAO surgery and behavioural assessment was possible in this model (with some caveats discussed in manuscript). Conclusions: This study shows MCAO is possible in aged, obese rats. However, this model is not ideal for recapitulating the complex comorbidities commonly seen in stroke patients.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_026 ◽

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.

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Fecal Microbiota Perspective for Evaluation of Prebiotic Potential of Bamboo Hemicellulose Hydrolysate in Mice: A Preliminary Study

Microorganisms ◽

10.3390/microorganisms9050888 ◽

2021 ◽

Vol 9 (5) ◽

pp. 888

Author(s):

Nao Ikeyama ◽

Mitsuo Sakamoto ◽

Moriya Ohkuma ◽

Shigeru Hiramoto ◽

Jianpeng Wang ◽

...

Keyword(s):

High Fat Diet ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Normal Diet ◽

Rrna Gene ◽

Hemicellulose Hydrolysate ◽

High Fat ◽

Fatty Acid Production ◽

The Family

Bamboo hemicellulose hydrolysate (BHH) may possess antihypercholesterolemic activity; however, this activity requires further comprehensive study to assess the prebiotic mechanisms of BHH in vivo. Here, we used high-throughput 16S rRNA gene sequencing to preliminarily investigate the correlations between BHH and the fecal microbiomes of three groups of mice fed either a normal diet, a high-fat diet, or a high-fat diet supplemented with 5% BHH for 5 weeks. Alpha diversity (within community) was nonsignificant for all groups; however, beta diversity analysis among communities showed that 5% BHH suppressed the significant changes induced by the high-fat diet. The Firmicutes/Bacteroidetes ratio, the family S24-7 within the order Bacteroidales, the family Lachnospiraceae and several cellulolytic taxa were slightly ameliorated in the BHH group. These results indicated that BHH supplementation influenced the gut bacterial community and suppressed the high-fat diet-induced alterations. Additionally, BHH significantly lowered the serum cholesterol levels and fecal pH. Improving short-chain fatty acid production for all of the bacterial communities in the mouse guts may induce this effect. Thus, the prebiotic potential of BHH should be evaluated considering the gut microbial communities and their interactions.

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A dietary ketone ester mitigates histological outcomes of NAFLD and markers of fibrosis in high-fat diet fed mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00259.2020 ◽

2021 ◽

Author(s):

Mary P Moore ◽

Rory P Cunningham ◽

Rachel A. H. Davis ◽

Sarah E. Deemer ◽

Brandon M. Roberts ◽

...

Keyword(s):

High Fat Diet ◽

Inflammatory Markers ◽

Metabolic Diseases ◽

Stellate Cell ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Hepatic Markers ◽

Nafld Activity Score ◽

Ketone Ester

Nutritional ketosis as a therapeutic tool has extended to the treatment of metabolic diseases including - obesity, type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to determine whether dietary administration of the ketone ester (KE), R,S-1,3-butanediol diacetoacetate (BD-AcAc2), attenuates markers of hepatic stellate cell (HSC) activation and hepatic fibrosis in the context of high fat diet (HFD)-induced obesity. Six-week-old male C57BL/6J mice were placed on a 10-week ad libitum HFD (45% FAT, 32% CHO, 23% PRO). Mice were then randomized to 1 of 3 groups (n = 10 per group) for an additional 12 weeks: 1) control (CON), continuous HFD, 2) pair-fed (PF) to KE; and 3) KE (HFD+30% energy from BD-AcAc2, KE). KE feeding significantly reduced histological steatosis, inflammation and total NAFLD activity score vs CON, beyond improvements observed for calorie restriction alone (PF). Dietary KE supplementation also reduced the protein content and gene expression of pro-fibrotic markers (α-SMA, Col1a1, PDGF-β, MMP9) vs CON (p<0.05), beyond reductions observed for PF vs CON. Furthermore, KE feeding increased hepatic markers of anti-inflammatory M2 macrophages (CD163) and also reduced pro-inflammatory markers (TRAIL and CCN1) vs CON and PF (p ≤ 0.05), in the absence of changes in markers of total hepatic macrophage content (F4/80 and CD68; p > 0.05). These data highlight that the dietary ketone ester, BD-AcAc2, ameliorates histological NAFLD and inflammation and reduces pro-fibrotic and pro-inflammatory markers. Future studies to further explore potential mechanisms are warranted.

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The flavonoid-rich Quzhou Fructus Aurantii extract modulates gut microbiota and prevents obesity in high-fat diet-fed mice

Nutrition and Diabetes ◽

10.1038/s41387-019-0097-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 15

Author(s):

Yong-feng Bai ◽

Si-wei Wang ◽

Xiao-xiao Wang ◽

Yuan-yuan Weng ◽

Xue-yu Fan ◽

...

Keyword(s):

Gut Microbiota ◽

High Fat Diet ◽

Metabolic Diseases ◽

Liver Steatosis ◽

Chow Diet ◽

High Fat ◽

Gut Dysbiosis ◽

Gut Microbial Community ◽

Junction Proteins

Abstract Background Flavonoids are reported to modulate the composition of gut microbiota, which play an important role in preventing obesity and associated metabolic diseases. In this study, we investigated the effect of Total Flavonoids of Quzhou Fructus Aurantii Extract (TFQ) on gut microbial community in mice fed with a high-fat diet (HFD). Methods C57BL/6J mice were fed with either a chow diet or HFD with or without oral gavage of TFQ (300 mg/kg/day) for 12 weeks. Results Our data indicate TFQ significantly reduced obesity, inflammatio,n and liver steatosis. TFQ elevates the expression of tight junction proteins and reduces metabolic endotoxemia. In addition, TFQ treatment reverses HFD-induced gut dysbiosis, as indicated by the reduction of Firmicutes to Bacteroidetes ratio, the increase of genera Akkermansia and Alistipes, and the decrease of genera Dubosiella, Faecalibaculum, and Lactobacillus. Conclusion These findings support a prebiotic role of TFQ as a dietary supplement for the intervention of gut dysbiosis and obesity-related metabolic disorders.

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Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats

Molecules ◽

10.3390/molecules24071268 ◽

2019 ◽

Vol 24 (7) ◽

pp. 1268 ◽

Cited By ~ 1

Author(s):

Peipei Zhou ◽

Xiaolin Yang ◽

Zhonglin Yang ◽

Wenzhe Huang ◽

Junping Kou ◽

...

Keyword(s):

Intestinal Microbiota ◽

High Fat Diet ◽

Metabolic Diseases ◽

Therapeutic Drug ◽

Systematic Change ◽

Hypolipidemic Effect ◽

Model Group ◽

Sprague Dawley ◽

High Fat ◽

Sprague Dawley Rats

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.

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Modulation of Some Insulin Signaling Genes Due to Prenatal Rice Consumption

Iranian journal of diabetes and obesity ◽

10.18502/ijdo.v11i4.2880 ◽

2020 ◽

Author(s):

Bilyaminu Abubakar ◽

Norsharina Ismail ◽

Md Zuki Abubakar ◽

Maznah Ismail

Keyword(s):

Prenatal Exposure ◽

Insulin Signaling ◽

High Fat Diet ◽

Metabolic Diseases ◽

Brown Rice ◽

Male Rats ◽

Standard Diet ◽

High Fat ◽

Germinated Brown Rice ◽

White Rice

Objective: A clinically observable metabolic disorder often takes its root from modulation of transcriptional factors which in turn are responsible for perturbed protein expressions and their sequelae. Perinatal perturbations due to chronic prenatal exposure to a certain type of rice could predispose parents exposed to such ‘insult’ and their subsequent offsprings to metabolic diseases. Materials and Methods: We investigated the effect of chronic prenatal exposure to different types of rice (in context of a balanced normal diet and a high-fat diet) on some insulin signaling genes using nulliparous Sprague Dawley rats. The rats were exposed to various predetermined rice diets for 90 days. After returning them to standard chow, they were mated with male rats raised on standard chow. The resulting pups (F1) and dams were sacrificed and their tissues were examined for modulation of genes related to insulin signaling. Results: Our results show that dams fed with white rice in context of standard diet modulated MAPK 1 , M A F A 1 and S L C 2 A 2 . Also, germinated brown rice prevented dysregulation of MAPK1, and SLC2A2 in both dams and pups exposed to this diet in the context of a high-fat diet. In general, germinated brown rice retarded dysregulations due to high-fat diet exposure while white rice enhanced the dysregulatory effects of high-fat diet. Conclusion: We conclude that chronic prenatal exposure to a certain type of rice, could be a factor to modulation of some genes related to insulin signaling pathways and that these modulation could be inherited by at least one generation of offsprings.

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