Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice

Alterations of the gut microbiota and mucosal barrier are linked with metabolic diseases. Our aim was to investigate the potential benefit of the potential probiotic Bifidobacterium animalis ssp. lactis 420 in reducing high-fat diet-induced body weight gain and diabetes in mice. In the obesity model, C57Bl/6J mice were fed a high-fat diet (60 energy %) for 12 weeks, and gavaged daily with B. lactis 420 (109 cfu) or vehicle. In the diabetes model, mice were fed a high-fat, ketogenic diet (72 energy % fat) for 4 weeks, with a 6-week subsequent treatment with B. lactis 420 (108-1010 cfu/day) or vehicle, after which they were analysed for body composition. We also analysed glucose tolerance, plasma lipopolysaccharide and target tissue inflammation using only one of the B. lactis 420 groups (109 cfu/day). Intestinal bacterial translocation and adhesion were analysed in a separate experiment using an Escherichia coli gavage. Body fat mass was increased in both obese (10.7±0.8 g (mean ± standard error of mean) vs. 1.86±0.21 g, P<0.001) and diabetic mice (3.01±0.4 g vs. 1.14±0.15 g, P<0.001) compared to healthy controls. Treatment with B. lactis 420 significantly decreased fat mass in obese (7.83 ± 0.67 g, P=0.007 compared to obese with vehicle) and diabetic mice (1.89 ± 0.16 g, P=0.02 for highest dose). This was reflected as reduced weight gain and improved glucose tolerance. Furthermore, B. lactis 420 decreased plasma lipopolysaccharide levels (P<0.001), liver inflammation (P=0.04), and E. coli adhesion in the distal gut (P<0.05). In conclusion, B. lactis 420 reduces fat mass and glucose intolerance in both obese and diabetic mice. Reduced intestinal mucosal adherence and plasma lipopolysaccharide suggest a mechanism related to reduced translocation of gut microbes.

Download Full-text

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.

Download Full-text

Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22105390 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5390

Author(s):

Qianhui Zeng ◽

Nannan Wang ◽

Yaru Zhang ◽

Yuxuan Yang ◽

Shuangshuang Li ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Insulin Sensitivity ◽

Energy Metabolism ◽

Glucose Tolerance ◽

High Fat Diet ◽

Chow Diet ◽

High Fat ◽

Glycolipid Metabolism ◽

Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

Download Full-text

Abstract 037: Role of Pro-opiomelanocortin (POMC) Specific PTP1B in Differential Regulation of Blood Pressure, Liver Lipid Accumulation and Glucose Tolerance in Response to a High Fat Diet

Hypertension ◽

10.1161/hyp.68.suppl_1.037 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Nicola Aberdein ◽

Jussara M do Carmo ◽

Zhen Wang ◽

Taolin Fang ◽

Cecilia P de Lara ◽

...

Keyword(s):

Blood Pressure ◽

Glucose Tolerance ◽

Fat Mass ◽

Lipid Accumulation ◽

High Fat Diet ◽

Acute Stress ◽

Liver Lipid ◽

Liver Weight ◽

Metabolic Effects ◽

High Fat

Obese subjects are often resistant to leptin’s metabolic effects although blood pressure (BP) and sympathetic nervous system responses appear to be preserved. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin signaling, may play a role in promoting this selective leptin resistance and causing metabolic dysfunction in obesity. Our previous studies suggest that the chronic BP responses to leptin are mediated via activation of pro-opiomelanocortin (POMC) neurons. The goal of this study was to determine if PTP1B in POMC neurons differentially controls metabolic functions and BP in mice fed a high fat diet (HFD). Male mice with POMC specific PTP1B deletion (POMC/PTP1B -/- ) and littermate controls (PTP1B flox/flox ) were fed a HFD from 6 to 22 wks of age. Baseline BP after 16 weeks of a HFD (95±2 vs. 95±3 mmHg) and BP responses to acute stress (Δ32±0 vs. Δ32±6 mmHg), measured by telemetry, were not different in POMC/PTP1B -/- compared to control mice, respectively. Heart rate (HR) was not different in POMC/PTP1B -/- and control mice during acute stress (699±4 vs. 697±15 bpm, respectively). Total body weight (TBW) and fat mass were reduced at 20 weeks of age in POMC/PTP1B -/- compared to controls (36.7±0.1 vs. 42.0±1 g TBW and 12.7±0.4 vs. 16.1±1.0 g fat mass, respectively). Liver weight of POMC/PTP1B -/- mice was less than in controls, and this was evident even when liver weight was normalized as % of TBW (4.5±0.2 vs. 5.0±0.2 %). POMC/PTP1B -/- males had reduced liver lipid accumulation compared to controls as measured by EchoMRI (0.08±0.03 vs. 0.15±0.03 g/g liver weight). Glucose tolerance was also improved by 46% in POMC/PTP1B -/- compared to controls as measured by AUC, 25856±1683 vs. 47267±5616 mg/dLx120min, respectively. These findings indicate that PTP1B signaling in POMC neurons plays a crucial role in regulating liver lipid accumulation and glucose tolerance but does not appear to mediate changes in BP or BP responses to acute stress in mice fed a high HFD (supported by NHLBI-PO1HL51971 and NIGMS P20GM104357)

Download Full-text

Antiobesity Effect of a Novel Herbal Formulation LI85008F in High-Fat Diet-Induced Obese Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6612996 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Hak Joo Choi ◽

Hwa Young Kim ◽

Kyoung Sik Park

Keyword(s):

Weight Gain ◽

Body Fat ◽

Fat Mass ◽

High Fat Diet ◽

Body Weight Gain ◽

Whole Body ◽

Body Fat Mass ◽

Obese Mice ◽

High Fat ◽

Herbal Formulation

A variety of natural products have been explored for their antiobesity potential and widely used to develop dietary supplements for the prevention of weight gain from excess body fat. In an attempt to find a natural antiobesity agent, this study was designed to evaluate the antiobesity activity of a novel herbal formulation LI85008F composed of extracts from three medicinal plants in high-fat diet- (HFD-) induced obese mice. After the thirteen-week oral administration of the test materials to mice, the body weight gain, whole-body fat mass, adipose tissue weight, and the expression levels of obesity-related proteins were measured. Our results indicated that LI85008F can suppress body weight gain and lower whole-body fat mass in HFD-induced obese mice. Significant decreases in epididymal and retroperitoneal fat mass were observed in LI85008F-treated groups compared with the HFD-fed control group ( p < 0.05 ). Furthermore, the oral administration of LI85008F caused significant decreases in the expression level of adipogenic (C/EBPα and PPARγ) and lipogenic (ACC) markers and notable increases in the production level of thermogenetic (AMPKα, PGC1α and UCP1) and lipolytic (HSL) proteins. These findings suggest that LI85008F holds great promise for a novel herbal formulation with antiobesity activities, preventing body fat accumulation and altering lipid metabolism.

Download Full-text

Carbonyl Reductase 1 Overexpression in Adipose Amplifies Local Glucocorticoid Action and Impairs Glucose Tolerance in Lean Mice

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1639 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A806-A806

Author(s):

Rachel Bell ◽

Elisa Villalobos ◽

Mark Nixon ◽

Allende Miguelez-Crespo ◽

Matthew Sharp ◽

...

Keyword(s):

Adipose Tissue ◽

Glucose Tolerance ◽

Fat Mass ◽

High Fat Diet ◽

Fasting Glucose ◽

High Fat ◽

Male And Female ◽

Over Expression ◽

Female Mice ◽

Diet Induced Obesity

Abstract Glucocorticoids play a critical role in metabolic homeostasis. Chronic or excessive activation of the glucocorticoid receptor (GR) in adipose tissue contributes to metabolic disorders such as glucose intolerance and insulin resistance. Steroid-metabolising enzymes in adipose, such as 11β-HSD1 or 5α-reductase, modulate the activation of GR by converting primary glucocorticoids into more or less potent ligands. Carbonyl reductase 1 (CBR1) is a novel regulator of glucocorticoid metabolism, converting corticosterone/cortisol to 20β-dihydrocorticosterone/cortisol (20β-DHB/F); a metabolite which retains GR activity. CBR1 is abundant in adipose tissue and increased in obese adipose of mice and humans1 and increased Cbr1 expression is associated with increased fasting glucose1. We hypothesised that increased Cbr1/20β-DHB in obese adipose contributes to excessive GR activation and worsens glucose tolerance. We generated a novel murine model of adipose-specific Cbr1 over-expression (R26-Cbr1Adpq) by crossing conditional knock-in mice with Adiponectin-Cre mice. CBR1 protein and activity were doubled in subcutaneous adipose tissue of male and female R26-Cbr1Adpq mice compared with floxed controls; corresponding to a two-fold increase 20β-DHB (1.6 vs. 4.2ng/g adipose; P=0.0003; n=5-7/group). There were no differences in plasma 20β-DHB or corticosterone. Bodyweight, lean or fat mass, did not differ between male or female R26-Cbr1Adpq mice and floxed controls. Lean male R26-Cbr1Adpq mice had higher fasting glucose (9.5±0.3 vs. 8.4±0.3mmol/L; P=0.04) and worsened glucose tolerance (AUC 1819±66 vs. 1392±14; P=0.03). Female R26-Cbr1Adpq mice also had a worsened glucose tolerance but fasting glucose was not altered with genotype. There were no differences in fasting insulin or non-esterified fatty acid between genotypes in either sex. Expression of GR-induced genes Pnpla2, Gilz and Per1, were increased in adipose of R26-Cbr1Adpq mice. Following high-fat diet induced obesity, no differences in bodyweight, lean or fat mass, with genotype were observed in male and female mice, and genotype differences in fasting glucose and glucose tolerance were abolished. In conclusion, adipose-specific over-expression of Cbr1 in lean male and female mice led to increased levels of 20β-DHB in adipose but not plasma, and both sexes having worsened glucose tolerance. The influence of adipose CBR1/20β-DHB on glucose tolerance was not associated with altered fat mass or bodyweight and was attenuated by high-fat diet-induced obesity. These metabolic consequences of Cbr1 manipulation require careful consideration given the wide variation in CBR1 expression in the human population, the presence of inhibitors and enhancers in many foodstuffs and the proposed use of inhibitors as an adjunct for cancer treatment regimens. Reference: Morgan et al., Scientific Reports. 2017; 7.

Download Full-text

Gingerol supplementation does not change glucose tolerance, lipid profile and does not prevent weight gain in C57BL/6 mice fed a high-fat diet

Clinical Nutrition Experimental ◽

10.1016/j.yclnex.2020.05.001 ◽

2020 ◽

Vol 32 ◽

pp. 11-19

Author(s):

Aline Jose Coelho Moreira Zordan ◽

Caroline Bertoncini-Silva ◽

Anderson Gregorio Joaquim ◽

Marina Rodrigues ◽

Cássia Dias Machado ◽

...

Keyword(s):

Weight Gain ◽

Glucose Tolerance ◽

Lipid Profile ◽

High Fat Diet ◽

High Fat ◽

Prevent Weight Gain

Download Full-text

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.

Download Full-text

Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain

Physiological Genomics ◽

10.1152/physiolgenomics.00135.2017 ◽

2018 ◽

Vol 50 (8) ◽

pp. 605-614

Author(s):

Hong He ◽

Katie Holl ◽

Sarah DeBehnke ◽

Chay Teng Yeo ◽

Polly Hansen ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Knockout Mice ◽

High Fat Diet ◽

Wild Type ◽

High Fat ◽

Male And Female ◽

Female Mice

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.

Download Full-text