scholarly journals Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2007
Author(s):  
Fabio Takeo Sato ◽  
Yu Anne Yap ◽  
Amanda Rabello Crisma ◽  
Mariana Portovedo ◽  
Gilson Masahiro Murata ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Body Weight Gain ◽  
Short Chain Fatty Acids ◽  
Obese Mice ◽  
Novel Approach ◽  
Lower Body Weight ◽  
Inflammatory State ◽  
Insulin Responsiveness ◽  
Inflammatory Changes ◽  
Dependent Mechanism

Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of Il-1β and Tnf-a and increased Il-10, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.

scholarly journals Omega-3 Phospholipids from Krill Oil Enhance Intestinal Fatty Acid Oxidation More Effectively than Omega-3 Triacylglycerols in High-Fat Diet-Fed Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2037 ◽  
Author(s):  
Petra Kroupova ◽  
Evert M. van Schothorst ◽  
Jaap Keijer ◽  
Annelies Bunschoten ◽  
Martin Vodicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Acid Oxidation ◽  
Obese Mice ◽  
Krill Oil ◽  
Omega 3 ◽  
High Fat ◽  
Lower Body Weight

Antisteatotic effects of omega-3 fatty acids (Omega-3) in obese rodents seem to vary depending on the lipid form of their administration. Whether these effects could reflect changes in intestinal metabolism is unknown. Here, we compare Omega-3-containing phospholipids (krill oil; ω3PL-H) and triacylglycerols (ω3TG) in terms of their effects on morphology, gene expression and fatty acid (FA) oxidation in the small intestine. Male C57BL/6N mice were fed for 8 weeks with a high-fat diet (HFD) alone or supplemented with 30 mg/g diet of ω3TG or ω3PL-H. Omega-3 index, reflecting the bioavailability of Omega-3, reached 12.5% and 7.5% in the ω3PL-H and ω3TG groups, respectively. Compared to HFD mice, ω3PL-H but not ω3TG animals had lower body weight gain (−40%), mesenteric adipose tissue (−43%), and hepatic lipid content (−64%). The highest number and expression level of regulated intestinal genes was observed in ω3PL-H mice. The expression of FA ω-oxidation genes was enhanced in both Omega-3-supplemented groups, but gene expression within the FA β-oxidation pathway and functional palmitate oxidation in the proximal ileum was significantly increased only in ω3PL-H mice. In conclusion, enhanced intestinal FA oxidation could contribute to the strong antisteatotic effects of Omega-3 when administered as phospholipids to dietary obese mice.

Bofutsushosan Improves Gut Barrier Function with a Bloom of Akkermansia Muciniphila and Improves Glucose Metabolism in Diet-Induced Obese Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1990-P ◽  
Author(s):  
SHIHO FUJISAKA ◽  
ISAO USUI ◽  
ALLAH NAWAZ ◽  
YOSHIKO IGARASHI ◽  
TOMONOBU KADO ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Barrier Function ◽  
Obese Mice ◽  
Gut Barrier ◽  
Akkermansia Muciniphila ◽  
Gut Barrier Function

Intravenous Infusion in Dogs and Primates

1994 ◽  
Vol 13 (1) ◽  
pp. 40-47 ◽  
Author(s):  
C.J. Perkin ◽  
R. Stejskal
Keyword(s):  
Body Weight ◽  
Intravenous Infusion ◽  
Body Weight Gain ◽  
Femoral Vein ◽  
Blood Pressure Measurement ◽  
Recovery Period ◽  
Vena Cava ◽  
Test Material ◽  
Catheter Tip ◽  
Inflammatory Changes

Continuous intravenous infusion allows the intended clinical dosing regime to be better evaluated during preclinical studies. Depending on the test material and vehicle, infusion for up to 6 months in primates and 12 months in beagle dogs is possible, but 28 days is the most frequent duration. Under general anesthesia, medical grade catheters are placed in the vena cava via the femoral vein, passed subcutaneously, and exteriorized between the scapulae. A jacket and tether system are used to connect the catheter to an external pump for dosing and the animals are allowed to move freely within the cages. Dosing usually commences after a 1-week recovery period. Body weight gain, food intake, and general observations indicate that the procedure does not adversely affect the normal laboratory behavior of the animals. Test article infusion periods from a few minutes up to 24 h a day, 7 days a week are used; a low infusion rate ofsaline is used for the balance of the 24-h period. Dosage volumes up to 120 ml/kg/day can be infused for 28 days and larger volumes for shorter periods. Up to three separate catheters can be inserted to allow coadministration of compounds for assessment of potential interactions. Body weight, ophthalmoscopy, blood sampling, electrocardiography, and indirect blood pressure measurement can be performed during infusion. Histopathologic common changes in all species include thrombosis, proliferation of vascular intima, and various local inflammatory changes at the infusion site in the vicinity of the catheter tip. These generally are considered to be due to physical irritation by the catheter. Secondary changes include pulmonary microemboli or thrombosis and histiocytosis in hepatic sinusoids often with erythrophago-cytosis. The main findings associated with infusion of very large volumes are reticulocytosis and increased hematopoiesis. These spontaneous findings must be distinguished from those possibly related to administration of the test material and/or vehicle.

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

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.

scholarly journals Fish oil suppresses obesity more potently in lean mice than in diet-induced obese mice but ameliorates steatosis in such obese mice

2021 ◽  
Vol 85 (2) ◽  
pp. 421-429
Author(s):  
Sachiko Okue ◽  
Eimi Ishikawa ◽  
Ren Nakahara ◽  
Tsubasa Ito ◽  
Takumi Okura ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Fish Oil ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Food Efficiency ◽  
Lard Diet

ABSTRACT This study sought to clarify the antiobesity effects of fish oil (FO) in terms of prevention and amelioration. An isocaloric diet composed of lard or FO was given to lean C57BL/6J mice for the study of prevention and high-fat diet-induced obese (DIO) mice for the study of amelioration for 4 weeks. Body weight gain and food efficiency were potently suppressed by FO in lean mice compared to lard diet-fed mice. Uncoupling protein-1 (UCP-1) expression in inguinal white adipose tissue (WAT) was also significantly induced by FO in lean mice. FO also suppressed body weight gain and food efficiency in DIO mice but did not reduce body weight. FO ameliorated liver steatosis in DIO mice by mildly inducing UCP-1 in inguinal WAT. FO suppressed obesity more potently in lean mice than in DIO mice but ameliorated steatosis in the DIO mice.

Antibiotic-induced microbiome depletion alters renal glucose metabolism and exacerbates renal injury after ischemia-reperfusion injury in mice

2021 ◽  
Author(s):  
Yuika Osada ◽  
Shunsaku Nakagawa ◽  
Kanako Ishibe ◽  
Shota Takao ◽  
Aimi Shimazaki ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Kidney Injury ◽  
Short Chain Fatty Acids ◽  
Glucose Levels ◽  
The Impact

Recent studies have revealed the impact of antibiotic-induced microbiome depletion (AIMD) on host glucose homeostasis. The kidney has a critical role in systemic glucose homeostasis; however, information regarding the association between AIMD and renal glucose metabolism remains limited. Hence, we aimed to determine the effects of AIMD on renal glucose metabolism by inducing gut microbiome depletion using an antibiotic cocktail (ABX) composed of ampicillin, vancomycin, and levofloxacin in mice. The results showed that the bacterial 16s rRNA expression, luminal concentrations of short-chain fatty acids and bile acids, and plasma glucose levels were significantly lower in ABX-treated mice than in vehicle-treated mice. In addition, ABX treatment significantly reduced renal glucose and pyruvate levels. The mRNA expression levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the renal cortex were significantly higher in ABX-treated mice than in vehicle-treated mice. We further examined the impact of AIMD on the altered metabolic status in mice after ischemia-induced kidney injury. After exposure to ischemia for 60 min, the renal pyruvate concentrations were significantly lower in ABX-treated mice than in vehicle-treated mice. ABX treatment caused a more severe tubular injury after ischemia-reperfusion (IR). Our findings confirm that AIMD is associated with decreased pyruvate levels in the kidney, which may have been caused by the activation of renal gluconeogenesis. Thus, we hypothesized that AIMD would increase the vulnerability of the kidney to IR injury.

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