TRPC6 deficiency causes increased body weight and glucose intolerance in mice fed a normal diet but does not amplify the obesogenic effect of a high fat diet

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.

Download Full-text

Effects of Zinc Alpha2 Glycoprotein on Lipid Metabolism of Liver in High-Fat Diet-Induced Obese Mice

Hormone and Metabolic Research ◽

10.1055/s-0043-118910 ◽

2017 ◽

Vol 49 (10) ◽

pp. 793-800 ◽

Cited By ~ 9

Author(s):

Guoqiang Fan ◽

Yu Qiao ◽

Shixing Gao ◽

Jun Guo ◽

Ruqian Zhao ◽

...

Keyword(s):

Body Weight ◽

Lipid Metabolism ◽

High Fat Diet ◽

Recombinant Plasmid ◽

Diet Group ◽

Normal Diet ◽

Hormone Sensitive Lipase ◽

High Fat ◽

Hepatic Lipid ◽

Protein Levels

AbstractZinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.

Download Full-text

Angelica sinensis Suppresses Body Weight Gain and Alters Expression of the FTO Gene in High-Fat-Diet Induced Obese Mice

BioMed Research International ◽

10.1155/2017/6280972 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Tao Zhong ◽

Xiao-Yue Duan ◽

Hao Zhang ◽

Li Li ◽

Hong-Ping Zhang ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Cpg Island ◽

Body Weight Gain ◽

Methylation Status ◽

Normal Diet ◽

Angelica Sinensis ◽

Obese Mouse ◽

Obese Mice ◽

High Fat

The root of Angelica sinensis (RAS) is a traditional Chinese medicine used for preventing and treating various diseases. In this study, we assessed RAS supplementation effects on body weight and the FTO gene expression and methylation status in a high-fat-diet (HFD) induced obese mouse model. Female obese mice were divided into groups according to RAS dosage in diet as follows: normal diet, HFD diet (HC), HFD with low-dosage RAS (DL), HFD with medium-dosage RAS (DM), and HFD with high-dosage RAS (DH). After RAS supplementation for 4 weeks, body weight suppression and FTO expression in DH mice were significantly higher than in HC mice, whereas no significant change in FTO expression was detected between DM and DL mice or in their offspring. Bisulfite sequencing PCR (BSP) revealed that the CpG island in the FTO promoter was hypermethylated up to 95.44% in the HC group, 91.67% in the DH group, and 90.00% in the normal diet group. Histological examination showed that adipocytes in the DH group were smaller than those in the HC group, indicating a potential role of RAS in obesity. This study indicated that RAS could ameliorate obesity induced by HFD and that the molecular mechanism might be associated with the expression of the FTO gene.

Download Full-text

Evaluation of voglibose on body weight in rats

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20192178 ◽

2019 ◽

Vol 8 (6) ◽

pp. 1159

Author(s):

Sarita Mulkalwar ◽

Tanya Gupta ◽

Vishwanath Kulkarni ◽

A. V. Tilak ◽

B. T. Rane ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Body Weight ◽

High Fat Diet ◽

Normal Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Obesity Drugs

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.

Download Full-text

A Combination of Apple Vinegar Drink with Bacillus coagulans Ameliorates High Fat Diet-Induced Body Weight Gain, Insulin Resistance and Hepatic Steatosis

Nutrients ◽

10.3390/nu12092504 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2504

Author(s):

Raquel Urtasun ◽

Joana Díaz-Gómez ◽

Miriam Araña ◽

María José Pajares ◽

María Oneca ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

High Fat Diet ◽

Body Weight Gain ◽

Bacillus Coagulans ◽

Normal Diet ◽

High Fat ◽

Blood Biochemical ◽

Traditional Remedy

Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.

Download Full-text

Knockout of nephron ATP6AP2 impairs proximal tubule function and prevents high fat diet induced obesity in male mice

Endocrinology ◽

10.1210/endocr/bqab200 ◽

2021 ◽

Author(s):

Silas A Culver ◽

Safia Akhtar ◽

Callie Rountree-Jablin ◽

Susanna R Keller ◽

Helen P Cathro ◽

...

Keyword(s):

Body Weight ◽

Proximal Tubule ◽

Knockout Mice ◽

High Fat Diet ◽

Caloric Intake ◽

Normal Diet ◽

Male Mice ◽

High Fat ◽

Diet Induced Obesity ◽

Urinary Glucose

Abstract ATP6AP2 expression is increased in the nephron during high fat diet (HFD) and its knockout (ATP6AP2 KO) reduces body weight (WT) in mice. We evaluated the contribution of ATP6AP2 to urinary glucose (UG) and albumin (Ualb) handling during HFD. We hypothesized that nephron ATP6AP2 KO increases UG and Ualb and minimizes HFD-induced obesity. Eight-week old male C57BL/6J mice with inducible nephron specific ATP6AP2 KO and non-induced controls (C) were fed either normal diet (ND, 12% kcal fat) or HFD (45% kcal fat) for 6 months. ATP6AP2 KO mice on ND had 20% (p<0.01) lower WT compared to C. HFD fed mice had 41% (p<0.05) greater WT than ND fed C. In contrast, ATP6AP2 KO abrogated the increase in WT induced by HFD by 40% (p<0.05). Mice on HFD had less caloric intake compared to ND controls (p<0.01). There were no significant differences in metabolic rate between all groups. UG and Ualb was significantly increased in ATP6AP2 KO mice on both ND and HFD. ATP6AP2 KO showed greater levels of proximal tubule apoptosis and histologic evidence of proximal tubule injury. In conclusion, our results demonstrate that nephron specific ATP6AP2 KO is associated with glucosuria and albuminuria, most likely secondary to renal proximal tubule injury and/or dysfunction. Urinary loss of nutrients may have contributed to the reduced WT of knockout mice on ND and lack of WT gain in response to HFD. Future investigation should elucidate the mechanisms by which loss of renal ATP6AP2 causes proximal tubule injury and dysfunction.

Download Full-text

Effects of Hwangryunjihwang-tang on In Vitro Fertilization and Ovulation in Mice Fed a High-fat Diet

The American Journal of Chinese Medicine ◽

10.1142/s0192415x03000904 ◽

2003 ◽

Vol 31 (02) ◽

pp. 213-223

Author(s):

H. G. Choi ◽

D. H. Kwak ◽

J. Y. Kim ◽

Y. J. Choi ◽

B. S. Kil ◽

...

Keyword(s):

Body Weight ◽

Embryonic Development ◽

High Fat Diet ◽

Normal Diet ◽

The Body ◽

High Fat ◽

Reproductive Dysfunction ◽

Vitro Fertilization

It has been generally accepted that Hwangryunjihwang-tang (H-tang) is a useful prescription for treating polydipsia and to prevent obesity induced by a high-fat diet. The aim of this study was to clarify whether H-tang improved reproductive dysfunction caused by obesity in mice. Mice were fed a high density protein and lipid diet for 4 weeks, followed by administration of H-tang at 480 mg/kg body weight per day for 4 days. Thereafter, changes of body weight, ovulation rate, in vitro and in vivo fertilization, embryonic development and implantation rate were measured. H-tang markedly reduced the body weight of obese mice fed a high-fat diet, but not mice fed a normal diet. H-tang significantly improved ovulation rates, in vitro and in vivo fertilization rates and embryonic development. These results indicate pharmacological reversal of reproductive dysfunction caused by obesity, perhaps by adjusting internal secretions and metabolic functions.

Download Full-text

Anti-Obese Effect of Cinnamon Extracts Dietary Supplementation on Serum Lipids and Body Weight Gain in High-Fat-Diet Induced Obese Mice Model

Current Developments in Nutrition ◽

10.1093/cdn/nzab055_046 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1236-1236

Author(s):

Joohee Oh ◽

Hyun-Sook !Kim

Keyword(s):

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

Diet Group ◽

Normal Diet ◽

Obese Mice ◽

Mice Model ◽

High Fat ◽

Final Body Weight

Abstract Objectives Cinnamon is one of the oldest spices widely used in traditional medicine and also currently used by people all around the world. Cinnamon has been known for modulating metabolic disorders by regulating insulin sensitivity. The aim of this study was to investigate the anti-obese effects of cinnamon extracts in high-fat-diet induced obese mice model. Methods After a week of adaptation period, the 6-week-old male C57BL/6J mice were randomly divided into 4 groups (n = 11 for each group) of the normal diet group (ND), the high-fat-diet group (HF), the normal diet with 1% cinnamon extracts (NC), and the high-fat diet with 1% cinnamon extracts (HC). All groups were treated for 14 weeks. Results In final body weight and body weight gain, NC group was significantly lower than ND group and HC group was significantly lower than HF group (P = 0.000). In serum TG (Triglyceride) levels and TC (Total cholesterol) levels, NC group showed significantly decreased level compared to that of ND group and HC group represented significantly decreased level compared to that of HF group (P = 0.000). Conclusions The present data showed NC group and HC group showed lower final body weight and body weight gain than ND group and HF group. Also, NC group and HC group showed the decreased level of TG (Triglyceride) and TC (Total cholesterol) compared to ND group and HF group. The further indicators of insulin-related factors are in progress. Funding Sources This study received no external funding.

Download Full-text

Garcinia Mangostana Extract and Curcumin Ameliorate Oxidative Stress, Dyslipidemia, and Hyperglycemia in High Fat Diet-induced Obese Wistar Albino Rats

10.21203/rs.3.rs-122559/v1 ◽

2021 ◽

Author(s):

Ranyah Labban ◽

Hanan fawaz ◽

Ahmed Almnaizel ◽

May Al-Muammar ◽

Ramesa Bhat ◽

...

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

High Fat Diet ◽

Curcuma Longa ◽

Normal Weight ◽

Normal Diet ◽

Albino Rats ◽

High Fat ◽

Garcinia Mangostana ◽

Pharmacological Agents

Abstract Background:Obesity is a risk factor for several diseases related to oxidative stress, hyperlipidemia, and hyperglycemia. Several pharmacological agents have been used to treat obesity, but these commonly exhibit undesirable side effects. The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating selected biochemical markers of oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Methods:Male albino Wistar rats were divided into eight experimental groups, fed on a normal diet or high-fat diet (HFD), then given mangosteen extract (400 mg /kg body weight/day) and/or curcumin (80 mg/kg body weight/day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Results:Curcumin was found to be more effective in reducing BMI, while mangosteen extract was found to induce a significant increase in anti-atherogenic marker HDL-C, but was ineffective in reducing dyslipidemia. Mangosteen extract and curcumin effectively reduced blood glucose. Mangosteen did not exhibit any anti-oxidative effects in normal weight rats; however, it induced a significant increase in glutathione in obese rats. Conclusion:The present study demonstrated that mangosteen pericarp extract and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.

Download Full-text

Neuroprotective role of Ginkgobiloba and Rosuvastatin in CA1 region of Hippocampus against high fat diet induced neurotoxicity

Indian Journal of Clinical Anatomy and Physiology ◽

10.18231/j.ijcap.2021.042 ◽

2021 ◽

Vol 8 (3) ◽

pp. 179-189

Author(s):

Anil Kumar ◽

Anand Acharya ◽

Subhadra Devi Velichety ◽

Rajesh Vaderav

Keyword(s):

Body Weight ◽

Spatial Learning ◽

High Fat Diet ◽

Diet Group ◽

Normal Diet ◽

High Fat ◽

Ca1 Region ◽

Group I ◽

Branching Points

Diet rich in fat is one of the main risk factor for the development of Alzheimer’s disease. Studies have shown that diet rich in fat disrupts memory and learning. The present study evaluates the ameliorative role of Ginkgobiloba and Rosuvastatin against high fat diet induced neurotoxicity in CA1 (Corona Ammonis) region of hippocampus. Animals were randomly divided into six groups. Group I received normal diet, Group II received high fat diet, Group III & IV were treated with Ginkgobiloba 50mg/kg and 100mg/kg body weight, and Group V & VI were treated with Rosuvastatin 10mg/kg and 20 mg/kg body weight. All the rats were subjected to spatial learning (Morris water maze). Subsequently, rats were sacrificed and brains were removed. Golgi staining was done and CA1 neurons of hippocampus were traced using camera lucida. Dendritic branching points and dendritic intersections were quantified. Lipid profile and Super oxide (SOD) was also estimated.There was enhancement of spatial learning in treatment group rats. Furthermore, a significant increase in dendritic length and branching points was observed in CA1 region along with significant decrease in the Superoxide dismutase in rats treated with higher dose of Ginkgobiloba and Rosuvastatin. Present study concludes that Ginkgobiloba and Rosuvastatin in higher dose have protective role against high fat diet induced neurotoxicity in CA1 region.

Download Full-text