scholarly journals K27Q/K29Q mutations in sphingosine kinase 1 attenuate high-fat diet induced obesity and altered glucose homeostasis in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jing Xie ◽  
Yong Shao ◽  
Jin Liu ◽  
Meilan Cui ◽  
Xiuxiao Xiao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Metabolic Diseases ◽  
Sphingosine Kinase ◽  
Protective Role ◽  
Sphingolipid Metabolism ◽  
Acid Oxidation ◽  
Sphingosine Kinase 1 ◽  
High Fat ◽  
Triglyceride Accumulation ◽  
Altered Glucose

AbstractObesity and its associated metabolic disorders are increasingly impacting public health worldwide. Sphingosine kinase 1 (Sphk1) is a critical enzyme in sphingolipid metabolism that has been implicated in various metabolic syndromes. In this study, we developed a mouse model constitutively expressing pseudoacetylated mouse Sphk1 (QSPHK1) to study its role in regulating glucose and lipid metabolism. The results showed that QSPHK1 mice gained less body weight than wide type (WT) mice on a high-fat diet, and QSPHK1 mice had improved glucolipid metabolism and insulin. Moreover, QSPHK1 mice had alleviated hepatic triglyceride accumulation and had high-fat-diet-induced hepatic steatosis that occurred as a result of reduced lipogenesis and enhanced fatty acid oxidation, which were mediated by the AMPK/ACC axis and the FGF21/adiponectin axis. Collectively, this study provided evidence that the K27Q/K29Q mutations of Sphk1 could have a protective role in preventing obesity and the related metabolic diseases. Hence, our results contribute to further understanding of the biological functions of Sphk1, which has great pharmaceutical implications.

scholarly journals Germinated Soybean Embryo Extract Ameliorates Fatty Liver Injury in High-Fat Diet-Fed Obese Mice

2020 ◽  
Vol 13 (11) ◽  
pp. 380
Author(s):  
Doyoung Kwon ◽  
Sou Hyun Kim ◽  
Seung Won Son ◽  
Jinuk Seo ◽  
Tae Bin Jeong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Ethanolic Extract ◽  
The Body ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Triglyceride Accumulation ◽  
Germinated Soybean

Soybean is known to have diverse beneficial effects against human diseases, including obesity and its related metabolic disorders. Germinated soybean embryos are enriched with bioactive phytochemicals and known to inhibit diet-induced obesity in mice, but their effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. Here, we germinated soybean embryos for 24 h, and their ethanolic extract (GSEE, 15 and 45 mg/kg) was administered daily to mice fed with a high-fat diet (HFD) for 10 weeks. HFD significantly increased the weight of the body, liver and adipose tissue, as well as serum lipid markers, but soyasaponin Ab-rich GSEE alleviated these changes. Hepatic injury and triglyceride accumulation in HFD-fed mice were attenuated by GSEE via decreased lipid synthesis (SREBP1c) and increased fatty acid oxidation (p-AMPKα, PPARα, PGC1α, and ACOX) and lipid export (MTTP and ApoB). HFD-induced inflammation (TNF-α, IL-6, IL-1β, CD14, F4/80, iNOS, and COX2) was normalized by GSEE in mice livers. In adipose tissue, GSEE downregulated white adipose tissue (WAT) differentiation and lipogenesis (PPARγ, C/EBPα, and FAS) and induced browning genes (PGC1α, PRDM16, CIDEA, and UCP1), which could also beneficially affect the liver via lowering adipose tissue-related circulating lipid levels. Thus, our results suggest that GSEE can prevent HFD-induced NAFLD via inhibition of hepatic inflammation and restoration of lipid metabolisms in both liver and adipose tissue.

Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet

2015 ◽  
Vol 1851 (2) ◽  
pp. 210-219 ◽  
Author(s):  
Greg M. Kowalski ◽  
Joachim Kloehn ◽  
Micah L. Burch ◽  
Ahrathy Selathurai ◽  
Steven Hamley ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
High Fat ◽  
Triglyceride Content

scholarly journals TNFSF14-Derived Molecules as a Novel Treatment for Obesity and Type 2 Diabetes

2021 ◽  
Vol 22 (19) ◽  
pp. 10647
Author(s):  
Mark Agostino ◽  
Jennifer Rooney ◽  
Lakshini Herat ◽  
Jennifer Matthews ◽  
Allyson Simonds ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Liver Steatosis ◽  
Western World ◽  
Acid Oxidation ◽  
High Fat

Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with glucose intolerance and insulin resistance, often culminating in Type 2 diabetes (T2D). Importantly, our team has recently shown that the TNF superfamily (TNFSF) member protein, TNFSF14, has been reported to protect against high fat diet induced obesity and pre-diabetes. We hypothesized that mimics of TNFSF14 may therefore be valuable as anti-diabetic agents. In this study, we use in silico approaches to identify key regions of TNFSF14 responsible for binding to the Herpes virus entry mediator and Lymphotoxin β receptor. In vitro evaluation of a selection of optimised peptides identified six potentially therapeutic TNFSF14 peptides. We report that these peptides increased insulin and fatty acid oxidation signalling in skeletal muscle cells. We then selected one of these promising peptides to determine the efficacy to promote metabolic benefits in vivo. Importantly, the TNFSF14 peptide 7 reduced high fat diet-induced glucose intolerance, insulin resistance and hyperinsulinemia in a mouse model of obesity. In addition, we highlight that the TNFSF14 peptide 7 resulted in a marked reduction in liver steatosis and a concomitant increase in phospho-AMPK signalling. We conclude that TNFSF14-derived molecules positively regulate glucose homeostasis and lipid metabolism and may therefore open a completely novel therapeutic pathway for treating obesity and T2D.

scholarly journals Chinese Propolis Prevents Obesity and Metabolism Syndromes Induced by a High Fat Diet and Accompanied by an Altered Gut Microbiota Structure in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 959
Author(s):  
Yufei Zheng ◽  
Yuqi Wu ◽  
Lingchen Tao ◽  
Xi Chen ◽  
Trevor Joseph Jones ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Liver Weight ◽  
Dependent Manner ◽  
Male Mice ◽  
High Fat ◽  
16S Rrna Analysis ◽  
Triglyceride Accumulation ◽  
Chinese Propolis

The increasing incidence of obesity poses a great threat to public health worldwide. Recent reports also indicate the relevance of obesity in metabolic diseases. Chinese propolis (CP), as a well-studied natural nutraceutical, has shown a beneficial effect on alleviating diabetes mellitus. However, few studies have investigated the effect of CP on weight management and energy balance. We examined the beneficial effects of dietary CP on weight in high-fat diet-fed female and male mice and determined whether CP alters gut microbiota. In this study, dietary CP supplementation reduces body weight and improves insulin resistance in high-fat diet (HFD)-fed mice in a dose-dependent manner. CP treatment also reverses liver weight loss and triglyceride accumulation in association with hepatic steatosis. The 16S rRNA analysis of gut microbiota demonstrated that CP treatment modulates the composition in HFD-fed mice. Our study also suggests that male mice were more sensitive to CP treatment than female mice. Taken together, CP supplementation reduces weight gain and reverses gut microbiome dysbiosis induced by HFD. Further, the effects of CP treatment on metabolic biomarkers and microbiome structure differ by gender.

scholarly journals Overexpression of Sphingosine Kinase 1 Prevents Ceramide Accumulation and Ameliorates Muscle Insulin Resistance in High-Fat Diet-Fed Mice

Diabetes ◽  
2012 ◽  
Vol 61 (12) ◽  
pp. 3148-3155 ◽  
Author(s):  
C. R. Bruce ◽  
S. Risis ◽  
J. R. Babb ◽  
C. Yang ◽  
G. M. Kowalski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
High Fat ◽  
Muscle Insulin Resistance ◽  
Ceramide Accumulation

scholarly journals Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγPathway

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ming Gu ◽  
Shengjie Fan ◽  
Gaigai Liu ◽  
Lu Guo ◽  
Xiaobo Ding ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
High Fat ◽  
Wax Gourd

Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptorγ(PPARγ) transactivities and could decrease mRNA levels of PPARγand its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγand HMGCR signaling.

scholarly journals Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice

2021 ◽  
Vol 22 (8) ◽  
pp. 4277
Author(s):  
Marija Pinterić ◽  
Iva I. Podgorski ◽  
Marijana Popović Hadžija ◽  
Ivana Tartaro Bujak ◽  
Ana Tadijan ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Lipid Hydroperoxide ◽  
Metabolic Stress ◽  
Lipid Hydroperoxides ◽  
Ros Scavenging ◽  
High Fat ◽  
Preclinical Research ◽  
Female Mice

High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases.

scholarly journals Delayed Exercise Training Improves Obesity-Induced Chronic Kidney Disease by Activating AMPK Pathway in High-Fat Diet-Fed Mice

2020 ◽  
Vol 22 (1) ◽  
pp. 350
Author(s):  
Florian Juszczak ◽  
Maud Vlassembrouck ◽  
Olivia Botton ◽  
Thomas Zwakhals ◽  
Morgane Decarnoncle ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Exercise Training ◽  
High Fat Diet ◽  
Interstitial Fibrosis ◽  
Calorie Intake ◽  
Acid Oxidation ◽  
Obese Mice ◽  
High Fat ◽  
Ampk Pathway

Exercise training is now recognized as an interesting therapeutic strategy in managing obesity and its related disorders. However, there is still a lack of knowledge about its impact on obesity-induced chronic kidney disease (CKD). Here, we investigated the effects of a delayed protocol of endurance exercise training (EET) as well as the underlying mechanism in obese mice presenting CKD. Mice fed a high-fat diet (HFD) or a low-fat diet (LFD) for 12 weeks were subsequently submitted to an 8-weeks EET protocol. Delayed treatment with EET in obese mice prevented body weight gain associated with a reduced calorie intake. EET intervention counteracted obesity-related disorders including glucose intolerance, insulin resistance, dyslipidaemia and hepatic steatosis. Moreover, our data demonstrated for the first time the beneficial effects of EET on obesity-induced CKD as evidenced by an improvement of obesity-related glomerulopathy, tubulo-interstitial fibrosis, inflammation and oxidative stress. EET also prevented renal lipid depositions in the proximal tubule. These results were associated with an improvement of the AMPK pathway by EET in renal tissue. AMPK-mediated phosphorylation of ACC and ULK-1 were particularly enhanced leading to increased fatty acid oxidation and autophagy improvement with EET in obese mice.

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