scholarly journals Metformin ameliorates maternal high-fat diet-induced maternal dysbiosis and fetal liver apoptosis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Szu-Wei Huang ◽  
Yu-Che Ou ◽  
Kuo-Shu Tang ◽  
Hong-Ren Yu ◽  
Li-Tung Huang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Fetal Liver ◽  
Liver Steatosis ◽  
Chow Diet ◽  
Obese Women ◽  
Sprague Dawley ◽  
Maternal Weight ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Beneficial Effects

Abstract Background The deleterious effect of maternal high-fat diet (HFD) on the fetal rat liver may cause later development of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effect of maternal HFD-induced maternal hepatic steatosis and dysbiosis on the fetal liver and intestines, and the effect of prenatal metformin in a rat model. Methods Sprague–Dawley rats were assigned to three groups (N = 6 in each group). Before mating, the rats were randomly assigned to HFD or normal-chow diet (NCD) group for 7 weeks. After mating, the HFD group rats were continued with high-fat diet during pregnancy and some of the HFD group rats were co-treated with metformin (HFMf) via drinking water during pregnancy. All maternal rats and their fetuses were sacrificed on gestational day 21. The liver and intestinal tissues of both maternal and fetal rats were analyzed. In addition, microbial deoxyribonucleic acid extracted from the maternal fecal samples was analyzed. Results HFD resulted in maternal weight gain during pregnancy, intrahepatic lipid accumulation, and change in the serum short-chain fatty acid profile, intestinal tight junctions, and dysbiosis in maternal rats. The effect of HFD on maternal rats was alleviated by prenatal metformin, which also ameliorated inflammation and apoptosis in the fetal liver and intestines. Conclusions This study demonstrated the beneficial effects of prenatal metformin on maternal liver steatosis, focusing on the gut-liver axis. In addition, the present study indicates that prenatal metformin could ameliorate maternal HFD-induced inflammation and apoptosis in the fetal liver and intestines. This beneficial effect of in-utero exposure of metformin on fetal liver and intestines has not been reported. This study supports the use of prenatal metformin for pregnant obese women.

scholarly journals Citrus Peel Extract Ameliorates High-Fat Diet-Induced NAFLD via Activation of AMPK Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 673 ◽  
Author(s):  
Geum-Hwa Lee ◽  
Cheng Peng ◽  
Seon-Ah Park ◽  
The-Hiep Hoang ◽  
Hwa-Young Lee ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Liver Steatosis ◽  
The Elderly ◽  
Underlying Mechanism ◽  
Chow Diet ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Citrus Peel ◽  
Ampk Signaling ◽  
Normal Chow

Non-alcoholic fatty liver disease (NAFLD) is prevalent in the elderly population, and has symptoms ranging from liver steatosis to advanced fibrosis. Citrus peel extracts (CPEs) contain compounds that potentially improve dyslipidemia; however, the mechanism of action and effects on hepatic steatosis regulation remains unclear. Current study was aimed to investigate the protective effect of CPEs extracted through hot-air drying (CPEW) and freeze-drying (CPEF) and the underlying mechanism in a rat model of high-fat diet-induced NAFLD. The high-fat diet (HFD)-fed rats showed significant increase in total cholesterol, alanine aminotransferase (ALT), triglycerides, aspartate aminotransferase (AST), and lipid peroxidation compared to the normal chow-diet (NCD) group rats; but CPEW and CPEF limited this effect. CPEW and CPEF supplementation reduced both hepatocyte steatosis and fat accumulation involving the regulatory effect of mTORC1. Collectively, CPEW and CPEF protected deterioration of liver steatosis with AMPK activation and regulating ROS accumulation associated with interstitial disorders, which are also associated with endoplasmic reticulum (ER) redox. Thus, the application of CPEW and CPEF may lead to the development of novel therapeutic or preventive agents against NAFLD.

scholarly journals Phytosterol esters attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease rats fed a high-fat diet

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lihua Song ◽  
Dan Qu ◽  
Qing Zhang ◽  
Jing jiang ◽  
Haiyue Zhou ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Hepatic Tissue ◽  
High Dose ◽  
Chow Diet ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Stress ◽  
Beneficial Effects ◽  
Ppar Γ ◽  
Phytosterol Esters

Abstract Given the adverse effects of drugs used for NAFLD treatment, identifying novel and effective natural compound to prevent NAFLD is urgently needed. In the present study, the effects of phytosterol esters (PSEs) on NAFLD were explored. Adult SD rats were randomized into five groups: normal chow diet (NC), high-fat diet (HF), low-, medium- and high-dose PSE treatment plus high-fat diet groups (PSEL, PSEM, and PSEH). Our results showed that the levels of LDL-C in the PSEL group and hepatic TG, TC, and FFA in the three PSEs groups were significantly decreased. Notably, the uric acid (UA) level was significantly decreased by PSEs intervention. The hepatic inflammatory stress was ameliorated via the inhibition of the cytokines, including TGF-β, IL-6, IL-10 and CRP in the PSEs intervention groups. Further, the oxidative status was improved by PSE treatment through adjusting the enzyme activity (SOD and XOD) and decreasing the MDA level. These beneficial effects of PSE may have been partly due to its regulation on the expression of TGF-β1, TGF-β2, TNF-α, UCP-2, PPAR-α and PPAR-γ in hepatic tissue at both mRNA and protein level. The results of this study suggest that PSEs may be used as therapeutic agents for the prevention and progression of NAFLD and that hyperuricemia is induced by high-fat diet consumption.

scholarly journals CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high-fat-fed C57BL/6 mice

2019 ◽  
Vol 317 (6) ◽  
pp. E973-E983 ◽  
Author(s):  
Annie Hasib ◽  
Chandani K. Hennayake ◽  
Deanna P. Bracy ◽  
Aimée R. Bugler-Lamb ◽  
Louise Lantier ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
High Fat Diet ◽  
Critical Role ◽  
Chow Diet ◽  
Wild Type ◽  
High Fat ◽  
Insulin Resistant ◽  
Beneficial Effects

Extracellular matrix hyaluronan is increased in skeletal muscle of high-fat-fed insulin-resistant mice, and reduction of hyaluronan by PEGPH20 hyaluronidase ameliorates diet-induced insulin resistance (IR). CD44, the main hyaluronan receptor, is positively correlated with type 2 diabetes. This study determines the role of CD44 in skeletal muscle IR. Global CD44-deficient ( cd44−/−) mice and wild-type littermates ( cd44+/+) were fed a chow diet or 60% high-fat diet for 16 wk. High-fat-fed cd44−/− mice were also treated with PEGPH20 to evaluate its CD44-dependent action. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (ICv). High-fat feeding increased muscle CD44 protein expression. In the absence of differences in body weight and composition, despite lower clamp insulin during ICv, the cd44−/− mice had sustained glucose infusion rate (GIR) regardless of diet. High-fat diet-induced muscle IR as evidenced by decreased muscle glucose uptake (Rg) was exhibited in cd44+/+ mice but absent in cd44−/− mice. Moreover, gastrocnemius Rg remained unchanged between genotypes on chow diet but was increased in high-fat-fed cd44−/− compared with cd44+/+ when normalized to clamp insulin concentrations. Ameliorated muscle IR in high-fat-fed cd44−/− mice was associated with increased vascularization. In contrast to previously observed increases in wild-type mice, PEGPH20 treatment in high-fat-fed cd44−/− mice did not change GIR or muscle Rg during ICv, suggesting a CD44-dependent action. In conclusion, genetic CD44 deletion improves muscle IR, and the beneficial effects of PEGPH20 are CD44-dependent. These results suggest a critical role of CD44 in promoting hyaluronan-mediated muscle IR, therefore representing a potential therapeutic target for diabetes.

scholarly journals Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity

2019 ◽  
Vol 8 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Anna C Simcocks ◽  
Kayte A Jenkin ◽  
Lannie O’Keefe ◽  
Chrishan S Samuel ◽  
Michael L Mathai ◽  
...  
Keyword(s):  
Body Weight ◽  
G Protein ◽  
High Fat Diet ◽  
Chow Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
G Protein Coupled Receptor ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
G Protein Coupled

Atypical cannabinoid compounds O-1602 and O-1918 are ligands for the putative cannabinoid receptors G protein-coupled receptor 55 and G protein-coupled receptor 18. The role of O-1602 and O-1918 in attenuating obesity and obesity-related pathologies is unknown. Therefore, we aimed to determine the role that either compound had on body weight and body composition, renal and hepatic function in diet-induced obesity. Male Sprague–Dawley rats were fed a high-fat diet (40% digestible energy from lipids) or a standard chow diet for 10 weeks. In a separate cohort, male Sprague–Dawley rats were fed a high-fat diet for 9 weeks and then injected daily with 5 mg/kg O-1602, 1 mg/kg O-1918 or vehicle (0.9% saline/0.75% Tween 80) for a further 6 weeks. Our data demonstrated that high-fat feeding upregulates whole kidney G protein receptor 55 expression. In diet-induced obesity, we also demonstrated O-1602 reduces body weight, body fat and improves albuminuria. Despite this, treatment with O-1602 resulted in gross morphological changes in the liver and kidney. Treatment with O-1918 improved albuminuria, but did not alter body weight or fat composition. In addition, treatment with O-1918 also upregulated circulation of pro-inflammatory cytokines including IL-1α, IL-2, IL-17α, IL-18 and RANTES as well as plasma AST. Thus O-1602 and O-1918 appear not to be suitable treatments for obesity and related comorbidities, due to their effects on organ morphology and pro-inflammatory signaling in obesity.

scholarly journals Integrated Transcriptomic and Translatomic Inquiry of the Role of Betaine on Lipid Metabolic Dysregulation Induced by a High-Fat Diet

2021 ◽  
Vol 8 ◽  
Author(s):  
Tengda Huang ◽  
Lin Yu ◽  
Hongyuan Pan ◽  
Zeqiang Ma ◽  
Tian Wu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
High Fat Diet ◽  
Liver Lipid ◽  
Liver Steatosis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Translational Efficiency ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Translational Level

An excessive high-fat/energy diet is a major cause of obesity and linked complications, such as non-alcoholic fatty liver disease (NAFLD). Betaine has been shown to effectively improve hepatic lipid metabolism. However, the mechanistic basis for this improvement is largely unknown. Herein, integration of mRNA sequencing and ribosome footprints profiling (Ribo-seq) was used to investigate the means by which betaine alleviates liver lipid metabolic disorders induced by a high-fat diet. For the transcriptome, gene set enrichment analysis demonstrated betaine to reduce liver steatosis by up-regulation of fatty acid beta oxidation, lipid oxidation, and fatty acid catabolic processes. For the translatome, 574 differentially expressed genes were identified, 17 of which were associated with the NAFLD pathway. By combined analysis of transcriptome and translatome, we found that betaine had the greater effect on NAFLD at the translational level. Further, betaine decreased translational efficiency (TE) for IDI1, CYP51A1, TM7SF2, and APOA4, which are related to lipid biosynthesis. In summary, this study demonstrated betaine alleviating lipid metabolic dysfunction at the translational level. The transcriptome and translatome data integration approach used herein provides for a new understanding of the means by which to treat NAFLD.

scholarly journals Diverse Effects of Different Akkermansia muciniphila Genotypes on Brown Adipose Tissue Inflammation and Whitening in a High-fat-diet Murine Model

2019 ◽  
Author(s):  
Lulu Deng ◽  
Zihao Ou ◽  
Dongquan Huang ◽  
Chong Li ◽  
Zhi Lu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Chow Diet ◽  
High Fat ◽  
Akkermansia Muciniphila ◽  
Brown Adipose

Abstract Background The study aimed to investigate the differences of different Akkermansia muciniphila (A.muciniphila) genotypes on metabolic protective effects in mice with high-fat diet and explore possible mechanisms. Methods Male C57BL/6 mice were randomly divided into 6 groups, including high-fat diet (HFD)+ A.muciniphila I/II/PBS group, normal chow diet (NCD)+A.muciniphila I/ II /PBS group, respectively. Dietary intervention and A.muciniphila gavage were performed simultaneously. Blood glucose and lipid metabolism, brown adipose morphology and activities, and intestinal barrier function were examined after the mice were sacrificed. Results A.muciniphila gavage improved the impaired glucose tolerance, hyperlipidemia and liver steatosis in HFD mice, and that A.muciniphila II was not as effective as A.muciniphila I. This phenomenon might be because A.muciniphila I intervention significantly inhibited brown adipose tissue whitening and inflammation induced by HFD, by repairing the intestinal barrier and relieving endotoxemia. A.muciniphila II did not display the same results as A.muciniphila I in HFD mice, but had stronger effects in the NCD mice. Conclusions This study mainly reveals the distinct functions of different A.muciniphila genotypes on diet-induced obesity, suggesting that different A.muciniphila genotypes may play inequitable roles in pathological conditions through distinct action pathways.

scholarly journals Low-Intensity Exercise Training Additionally Increases Mitochondrial Dynamics Caused by High-Fat Diet (HFD) but Has No Additional Effect on Mitochondrial Biogenesis in Fast-Twitch Muscle by HFD

2020 ◽  
Vol 17 (15) ◽  
pp. 5461
Author(s):  
Yun Seok Kang ◽  
Donghun Seong ◽  
Jae Cheol Kim ◽  
Sang Hyun Kim
Keyword(s):  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
High Fat Diet ◽  
Mitochondrial Dynamics ◽  
Chow Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Related Factors ◽  
Mitochondrial Dynamic ◽  
Low Intensity

This study examines how the high-fat diet (HFD) affects mitochondrial dynamics and biogenesis, and also whether combining it with low-intensity endurance exercise adds to these effects. Six 8-week-old male Sprague–Dawley (SD) rats were put on control (CON; standard chow diet), HF (HFD intake), and HFEx (HFD + low-intensity treadmill exercise) for 6 weeks. As a result, no change in body weight was observed among the groups. However, epididymal fat mass increased significantly in the two groups that had been given HFD. Blood free fatty acid (FFA) also increased significantly in the HF group. While HFD increased insulin resistance (IR), this was improved significantly in the HFEx group. HFD also significantly increased mitochondrial biogenesis-related factors (PPARδ, PGC-1α, and mtTFA) and mitochondrial electron transport chain proteins; however, no additional effect from exercise was observed. Mitochondrial dynamic-related factors were also affected: Mfn2 increased significantly in the HFEx group, while Drp1 and Fis-1 increased significantly in both the HF and HFEx groups. The number of mitochondria in the subsarcolemmal region, and their size in the subsarcolemmal and intermyofibrillar regions, also increased significantly in the HFEx group. Taken overall, these results show that HFD in combination with low-intensity endurance exercise has no additive effect on mitochondrial biogenesis, although it does have such an effect on mitochondrial dynamics by improving IR.

scholarly journals HISTOPATHOLOGICAL STUDY OF THE PROTECTIVE EFFECT OF SPIRULINA PLATENSIS ON FETAL LIVER OF MICE WITH ACUTE FATTY LIVER OF PREGNANCY

2020 ◽  
pp. 201-207
Author(s):  
MARYAM KARGARZADEH ◽  
MITRA HEIDARI NASRABADI ◽  
AREZO DASTPAK ◽  
HANIEH KARGARZADEH
Keyword(s):  
Fatty Liver ◽  
Protective Effect ◽  
High Fat Diet ◽  
Spirulina Platensis ◽  
Fetal Liver ◽  
Liver Steatosis ◽  
High Fat ◽  
Small Female ◽  
Female Mice ◽  
Acute Fatty Liver

Objective: The protective effect of Spirulina platensis on the fetal liver of mice with acute fatty liver of pregnancy was investigated. Methods: Small female mice were divided into four groups: A control group with a standard diet, a high-fat diet to induce liver steatosis, a high-fat diet plus Spirulina, and a high-fat diet plus Simvastatin given through gavage to protect the liver against steatosis. After 2 months, the female mice became pregnant by polygamy method at the same time they were treated by different diets. On day 17, the fetuses were removed by C-section, and histological studies were carried out on their livers. Results: The results showed a significant decrease in liver steatosis in the group treated by Spirulina compared with the other groups (p<0.05). The fatty liver of pregnancy could lead to liver failure and death in both mother and fetus, and medications like Simvastatin that is used for the treatment of fatty liver are harmful to the fetus. However, Spirulina shows a positive effect on the treatment of both fetus and mother. Conclusions: The results of this study show that Spirulina is an effective medical supplement in the treatment of fatty liver of pregnancy.

scholarly journals Chinese Traditional Fermented Soy Sauce Exerts Protective Effects against High-Fat and High-Salt Diet-Induced Hypertension in Sprague-Dawley Rats by Improving Adipogenesis and Renin-Angiotensin-Aldosterone System Activity

Fermentation ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 52
Author(s):  
Bao Zhong ◽  
Eun-Gyung Mun ◽  
Jin-Xi Wang ◽  
Youn-Soo Cha
Keyword(s):  
High Fat Diet ◽  
High Salt ◽  
Soy Sauce ◽  
Fermented Foods ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
High Fat ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Beneficial Effects

Although high-fat and high-salt diets are considered risk factors for hypertension, the intake of salty soybean-based fermented foods has beneficial effects. This study explored the potential of Chinese traditional fermented soy sauce (CTFSS) in preventing hypertension by analyzing its effects on adipogenesis and the renin-angiotensin-aldosterone system (RAAS). Male Sprague-Dawley (SD) rats were divided into four groups (n = 6): normal diet (ND), high-fat diet (HD), high-fat diet with saline (HDS, NaCl-8%), and high-fat diet with Chinese traditional soy sauce (HDCTS, NaCl-8%). Each group is administrated 12 weeks by oral gavage as 10 mL/kg dose, respectively. CTFSS supplementation resulted in significantly lower body weight, epididymal fat weight, and systolic blood pressure. Additionally, it decreased the serum total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), renin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and aldosterone levels. It also increased the urinary volume and improved sodium and potassium ion balance. The gene levels showed significant enhancements in the mRNA levels of renin-angiotensin-aldosterone system-related and adipogenesis-related genes. In addition, CTFSS may prevent hypertension-associated kidney injury. Therefore, this study demonstrates that CTFSS has no harmful effects on hypertension. In contrast, the beneficial effects of CTFSS intake in ameliorating hypertension were shown.

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