Djulis Hull Improves Insulin Resistance and Modulates the Gut Microbiota in High-Fat Diet (HFD)-Induced Hyperglycaemia

In this study, we annotated the major flavonoid glycoside, rutin, of djulis hull crude extract using a Global Natural Products Social Molecular Networking (GNPS) library and its MS/MS spectra. To evaluate the protective effect of djulis hull crude extract and rutin on glucose tolerance, we fed mice a high-fat diet (HFD) for 16 weeks to induce hyperglycaemia. These results showed that crude extract significantly decreased HFD-induced elevation in the area under the curve (AUC) of weekly random blood glucose and oral glucose tolerance tests (OGTT), homeostasis model assessment (HOMA-IR), and advanced glycation end product (AGE) levels, and significantly increased pIRS1 and Glut4 protein expression in epididymal white adipose tissue (eWAT) and liver. Furthermore, the HFD-induced reduction in the activity of glutathione peroxidase (GPx) and catalase (CAT) was reversed by crude extract. In addition, ZO-1 and occludin protein expression in the colon was markedly downregulated in HFD-fed mice, resulting in decreased intestinal permeability and lipopolysaccharide (LPS) translocation, but were restored following crude extract. Moreover, the crude extract intervention had a profound effect on the alpha diversity and microbial community in the gut microbiota. Therefore, djulis hull crude extract could improve blood glucose and increase insulin receptor sensitivity in HFD-induced hyperglycaemia, which is likely due to its modulation of the gut microbiota, preservation of the integrity of the intestinal barrier to reduce body inflammation, increased antioxidant activity, and modulation of insulin signalling.

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Lactobacillus sakei OK67 ameliorates high-fat diet–induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression

Nutrition Research ◽

10.1016/j.nutres.2015.12.001 ◽

2016 ◽

Vol 36 (4) ◽

pp. 337-348 ◽

Cited By ~ 66

Author(s):

Su-Min Lim ◽

Jin-Ju Jeong ◽

Kyung Hee Woo ◽

Myung Joo Han ◽

Dong-Hyun Kim

Keyword(s):

Blood Glucose ◽

Gut Microbiota ◽

Protein Expression ◽

Tight Junction ◽

High Fat Diet ◽

Lactobacillus Sakei ◽

High Fat ◽

Tight Junction Protein Expression ◽

Junction Protein ◽

Obesity In Mice

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Comparison between pre-exercise casein peptide and intact casein supplementation on glucose tolerance in mice fed a high-fat diet

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0485 ◽

2018 ◽

Vol 43 (4) ◽

pp. 355-362 ◽

Cited By ~ 1

Author(s):

Yutaka Matsunaga ◽

Yuki Tamura ◽

Yasuyuki Sakata ◽

Yudai Nonaka ◽

Noriko Saito ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Tolerance ◽

Endurance Training ◽

Soleus Muscle ◽

High Fat Diet ◽

Glucose Transporter ◽

Area Under The Curve ◽

Abdominal Fat ◽

Oral Glucose ◽

High Fat

We hypothesized that along with exercise, casein peptide supplementation would have a higher impact on improving glucose tolerance than intact casein. Male 6-week-old ICR mice were provided a high-fat diet to induce obesity and glucose intolerance. The mice were randomly divided into 4 treatment groups: control (Con), endurance training (Tr), endurance training with intact casein supplementation (Cas+Tr), and endurance training with casein peptide supplementation (CP+Tr). The mice in each group were orally administrated water, intact casein, or casein peptide (1.0 mg/g body weight, every day), and then subjected to endurance training (15–25 m/min, 60 min, 5 times/week for 4 weeks) on a motor-driven treadmill 30 min after ingestion. Our results revealed that total intra-abdominal fat was significantly lower in CP+Tr than in Con (p < 0.05). Following an oral glucose tolerance test, the blood glucose area under the curve (AUC) was found to be significantly smaller for CP+Tr than for Con (p < 0.05). Moreover, in the soleus muscle, glucose transporter 4 (GLUT4) protein levels were significantly higher in CP+Tr than in Con (p < 0.01). However, intra-abdominal fat, blood glucose AUC, and GLUT4 protein content in the soleus muscle did not alter in Tr and Cas+Tr when compared with Con. These observations suggest that pre-exercise casein peptide supplementation has a higher effect on improving glucose tolerance than intact casein does in mice fed a high-fat diet.

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Aldehyde Dehydrogenase Mutation Exacerbated High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease with Gut Microbiota Remodeling in Male Mice

Biology ◽

10.3390/biology10080737 ◽

2021 ◽

Vol 10 (8) ◽

pp. 737

Author(s):

Sien-Sing Yang ◽

Yi-Hsun Chen ◽

Jui-Ting Hu ◽

Ching-Feng Chiu ◽

Shao-Wen Hung ◽

...

Keyword(s):

Gut Microbiota ◽

Aldehyde Dehydrogenase ◽

High Fat Diet ◽

Elevated Serum ◽

The Body ◽

Oral Glucose ◽

Model Assessment ◽

Male Mice ◽

High Fat ◽

Female Mice

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a critical enzyme involved in ethanol clearance in acetaldehyde metabolism and plays a key role in protecting the liver. The ALDH2*2 mutation causes a significant decrease in acetaldehyde scavenging capacity, leading to the accumulation of acetaldehyde after consuming alcohol. The prevalence of the ALDH2*2 variant is in 45% of Taiwanese individuals. ALDH2 reportedly has protective properties on myocardial damage, stroke, and diabetic retina damage. However, the effects of ALDH2 in the modulation of metabolic syndromes remain unclear. This study evaluates the roles of ALDH2 in a high-fat-diet-induced metabolic syndrome in mice. Male (M) and female (F) wild-type (WT) and ALDH2 knock-in C57BL/6J mice (4–5 weeks old) were fed a high-fat diet for 16 weeks. Results showed that the body and white-adipose-tissue weights were significantly increased in ALDH2-M compared to those in the other groups. We observed markedly elevated serum levels of alanine transaminase and glucose. Oral glucose-tolerance test and homeostasis-model assessment of insulin resistance (HOMA-IR) values were significantly higher in ALDH2-M mice than those in WT-M mice, with no observable differences in female mice. Abundant steatosis and inflammatory cells were observed in ALDH2-M, with significantly decreased expression of hepatic genes IRS2, GLUT4, and PGC-1α compared to that in WT-M. ALDH2 gene mutation also affected the β-diversity of gut microbiota in ALDH2-M resulting in the decreased abundance of Actinobacteria and an increase in Deferribacteres. Our results suggest that potential changes in gut microbiota may be associated with the defective ALDH2 exacerbation of high-fat-diet-induced liver diseases in male mice. However, female mice were not affected, and sex hormones may be an important factor that requires further investigation.

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Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

Nutrients ◽

10.3390/nu13051666 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1666

Author(s):

Dean S. Ross ◽

Tzu-Hsuan Yeh ◽

Shalinie King ◽

Julia Mathers ◽

Mark S. Rybchyn ◽

...

Keyword(s):

Glucose Tolerance ◽

Bone Formation ◽

Glucose Intolerance ◽

High Fat Diet ◽

Age Groups ◽

Oral Glucose ◽

Rna Expression ◽

High Fat ◽

Mineral Density ◽

Skeletal Fragility

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.

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Abstract 404: NLR Family, Pyrin Domain-containing 3 Knockout Rescues Cardiac Dysfunction Induced by High-fat Diet Feeding

Circulation Research ◽

10.1161/res.121.suppl_1.404 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Matthew R Peterson ◽

Samantha Haller ◽

Tracy Ta ◽

Luiza Bosch ◽

Aspen Smith ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Response ◽

Glucose Tolerance ◽

High Fat Diet ◽

Fasting Blood Glucose ◽

Left Ventricular ◽

Normal Diet ◽

High Fat ◽

Pyrin Domain

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p<0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p>0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p<0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p<0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p<0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p<0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p<0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p<0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p<0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p<0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p<0.001). Body weight explained 92% of variation in glucose tolerance (p<0.0001) and 69% of variation in fasting blood glucose (p<0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.

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Patchouli Alcohol from Pogostemon Cablin Prevents Development of Obesity and Improves Glucose Tolerance in High Fat Diet-induced Obese Mice (P06-107-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-107-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Jihye Lee ◽

Seong-Ho Lee

Keyword(s):

Body Weight ◽

Glucose Tolerance ◽

High Fat Diet ◽

Oral Glucose ◽

Male Mice ◽

Fat Pad ◽

High Fat ◽

Patchouli Alcohol ◽

Brown Adipose ◽

Pogostemon Cablin

Abstract Objectives Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin. Recently, we observed that patchouli alcohol reduced lipid accumulation in differentiated 3T3-L1 adipocytes and increased glucose uptake in differentiated C2C12 myocytes. This study was designed to investigate anti-obese and anti-diabetic activities of patchouli alcohol using high fat diet-induced obese mouse model. Methods Forty-eight 5-week old C57BL/6 J male mice were assigned into four groups and fed with 1) normal diet (control), 2) high fat diet, 3) high fat diet with gavaging 25 mg of patchouli alcohol/kg body weight and 4) high fat diet with gavaging 50 mg of patchouli alcohol/kg body weight. High fat diet or control diets were provided to each treatment group for four weeks and then different doses of patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered for following 8 weeks with the diet. At age of week 17, all animals were sacrificed, fat tissues were collected, and tissue weight was measured. In addition, twenty C57BL/6 J male mice were assigned into the same treatment groups above. At the end of the 8 weeks (age of week 17), the mice were fasted for 12 h and the oral glucose tolerance test was performed after intraperitoneal injection of 2 g of anhydrous glucose/kg body weight. The blood was collected from tail at 0, 15, 30, 90 and 120 min after injection and blood glucose level was analyzed using glucose meter. Results Treatment of patchouli alcohol (50 mg/kg body weight) significantly reduced body weight and accumulation of body fat pads which was highly induced by feeding of high fat diet. An analysis of individual fat pad weights (expressed as mg weight of fat pad/g body weight) revealed a significant decrease of epididymal and retroperitoneal fat pad in patchouli alcohol-treated mice whereas brown adipose tissue were not significantly altered. And, slightly improved glucose tolerance was observed at 90 and 120 minutes after glucose injection in mice treated with patchouli alcohol (50 mg/kg body weight) compared to those fed with high fat diet alone. Conclusions We propose a potential use of patchouli alcohol as an anti-obesity compound in obese population. Funding Sources NIFA Hatch grant. Supporting Tables, Images and/or Graphs

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Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00465.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. R332-R339 ◽

Cited By ~ 8

Author(s):

Jieyun Yin ◽

Jian Kuang ◽

Manisha Chandalia ◽

Demidmaa Tuvdendorj ◽

Batbayar Tumurbaatar ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acid ◽

Blood Glucose ◽

Insulin Sensitivity ◽

Free Fatty Acid ◽

Glucose Tolerance ◽

High Fat Diet ◽

Postprandial Glucose ◽

Tolerance Test ◽

High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

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Preventive Effects of Kaempferol on High-Fat Diet-Induced Obesity Complications in C57BL/6 Mice

BioMed Research International ◽

10.1155/2020/4532482 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Tieqiao Wang ◽

Qiaomin Wu ◽

Tingqi Zhao

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Blood Glucose ◽

Gut Microbiota ◽

Serum Cholesterol ◽

High Fat Diet ◽

Liver Weight ◽

Control Group ◽

High Fat ◽

High Blood Glucose

Kaempferol is a dietary flavanol that regulates cellular lipid and glucose metabolism. Its mechanism of action in preventing hepatic steatosis and obesity-related disorders has yet to be clarified. The purpose of this research was to examine kaempferol’s antiobesity effects in high-fat diet- (HFD-) fed mice and to investigate its impact on their gut microbiota. Using a completely randomized design, 30 mice were equally assigned to a control group, receiving a low-fat diet, an HFD group, receiving a high-fat diet, and an HFD+kaempferol group, receiving a high-fat diet and kaempferol doses of 200 mg/kg in the diet. After eight weeks, the HFD mice displayed substantial body and liver weight gain and high blood glucose and serum cholesterol levels. However, treatment with kaempferol moderated body and liver weight gain and elevation of blood glucose and serum cholesterol and triglyceride levels. Examination of 16S ribosomal RNA showed that HFD mice exhibited decreased microbial diversity, but kaempferol treatment maintained it to nearly the same levels as those in the control group. In conclusion, kaempferol can protect against obesity and insulin resistance in mice on a high-fat diet, partly through regulating their gut microbiota and moderating the decrease in insulin resistance.

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Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity

FEMS Microbiology Ecology ◽

10.1093/femsec/fiaa079 ◽

2020 ◽

Vol 96 (6) ◽

Cited By ~ 2

Author(s):

Sarah L Becker ◽

Edna Chiang ◽

Anna Plantinga ◽

Hannah V Carey ◽

Garret Suen ◽

...

Keyword(s):

Glucose Tolerance ◽

Gut Microbiota ◽

Glucose Intolerance ◽

High Fat Diet ◽

High Fat ◽

Low Fat ◽

Treatment Groups ◽

Low Fat Diet ◽

Taxonomic Groups ◽

Induced Changes

ABSTRACT Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia. After 10 weeks of treatment, mice consuming a high fat diet (60% kcal from fat) developed glucose intolerance and gained more weight than mice consuming a low fat diet. Stevia supplementation did not impact body weight or glucose intolerance. Differences in species richness and relative abundances of several phyla were observed in low fat groups compared to high fat, stevia and saccharin. We identified two operational taxonomic groups that contributed to differences in beta-diversity between the stevia and saccharin groups: Lactococcus and Akkermansia in females and Lactococcus in males. Our results demonstrate that stevia does not rescue high fat diet-induced changes in glucose tolerance or the microbiota, and that stevia results in similar alterations to the gut microbiota as saccharin when administered in concordance with a high fat diet.

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