Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA synthetase mRNA decrease

1997 ◽  
Vol 273 (1) ◽  
pp. E37-E45 ◽  
Author(s):  
S. Ikemoto ◽  
M. Takahashi ◽  
N. Tsunoda ◽  
K. Maruyama ◽  
H. Itakura ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Skeletal Muscles ◽  
Unsaturation Index ◽  
Sodium Cholate ◽  
Fat Absorption ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Triglyceride Accumulation ◽  
Responsive Element

The effects of sodium cholate on high-fat diet-induced hyperglycemia and obesity were investigated. Insulin resistance was estimated by measuring 2-deoxyglucose uptake in epitrochlearis muscles incubated in vitro. Addition of 0.5% cholate to high-safflower oil diet completely prevented high fat-induced hyperglycemia and obesity in C57BL/6J mice with a slight decrease of energy intake but with no inhibition of fat absorption. Furthermore, the addition of cholate decreased blood insulin levels and prevented high-fat diet-induced decrease of glucose uptake in epitrochlearis. However, there was no change in the unsaturation index of fatty acids in skeletal muscles and in GLUT-4 levels by cholate. In liver, cholate addition resulted in cholesterol accumulation and completely prevented high-fat diet-induced triglyceride accumulation. The changes of triglyceride level in the liver were paralleled to the changes of acyl-CoA synthetase (ACS) mRNA. ACS catalyzes the formation of acyl-CoA from fatty acid, and acyl-CoA is utilized for triglyceride formation in liver. ACS has a sterol-responsive element 1 in its promoter region. These data indicate that the favorable effects of cholate could be partly the result of downregulation of ACS mRNA.

scholarly journals Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Woo Nam ◽  
Seok Hyun Nam ◽  
Sung Phil Kim ◽  
Carol Levin ◽  
Mendel Friedman
Keyword(s):  
Weight Gain ◽  
High Fat Diet ◽  
Biological Activities ◽  
The Body ◽  
High Fat ◽  
In Vivo Models ◽  
Triglyceride Accumulation ◽  
In Cells

Abstract Background The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice. Methods Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations. Results The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound. Conclusion The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.

scholarly journals Lack of miR-379/miR-544 Cluster Resists High-Fat Diet-Induced Obesity and Prevents Hepatic Triglyceride Accumulation in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Congcong Cao ◽  
Peng Duan ◽  
Wencun Li ◽  
Yang Guo ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Leptin Receptor ◽  
Mirna Cluster ◽  
High Fat ◽  
Gene Expressions ◽  
Alcoholic Fatty Liver ◽  
Triglyceride Accumulation

Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Emerging evidence suggests that microRNAs (miRNAs) are essential for the metabolic homeostasis of liver tissues. Many hepatic miRNAs located in the miR-379/miR-544 cluster were significantly increased in leptin-receptor-deficient type 2 mice (db/db), a mouse model of diabetes. However, the function of the miR-379/miR-544 cluster in the process of hepatic steatosis remains unclear. Here, we report that the novel function of miR-379/miR-544 cluster in regulating obesity-mediated metabolic dysfunction. Genetical mutation of miR-379/miR-544 cluster in mice displayed resistance to high-fat diet (HFD)-induced obesity with moderate hepatic steatosis and hypertriglyceridemia. In vitro studies revealed that silencing of miR-379 in human hepatocellular carcinoma (HepG2) cells ameliorated palmitic acid-induced elevation of cellular triglycerides, and overexpression of miR-379 had the opposite effect. Moreover, Igf1r (Insulin-like growth factor 1 receptor) and Dlk1 (Delta-like homolog 1) were directly targeted by miR-379 and miR-329, respectively, and elevated in the livers of the miR-379/miR-544 cluster knockout mice fed on HFD. Further transcriptome analyses revealed that the hepatic gene expressions are dysregulated in miR-379/miR-544 knockout mice fed with HFD. Collectively, our findings identify the miR-379/miR-544 cluster as integral components of a regulatory circuit that functions under conditions of metabolic stress to control hepatic steatosis. Thus, this miRNA cluster provides potential targets for pharmacologic intervention in obesity and NAFLD.

scholarly journals Deletion of lysophosphatidylcholine acyltransferase3 in myeloid cells worsens hepatic steatosis after a high fat diet

2020 ◽  
pp. jlr.RA120000737
Author(s):  
Thibaut Bourgeois ◽  
Antoine Jalil ◽  
Charles Thomas ◽  
Charlene Magnani ◽  
Naig Le Guern ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Ldl Receptor ◽  
Myeloid Cells ◽  
Lipid Absorption ◽  
High Fat ◽  
Triglyceride Accumulation ◽  
Pufa Composition

Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3’s role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approx. 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation.

Hypoxic Exercise Training Promotes apelin/APJ Expression in Skeletal Muscles of High Fat Diet-Induced Obese Mice

2016 ◽  
Vol 24 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Weixiu Ji ◽  
Lijing Gong ◽  
Jianxiong Wang ◽  
Hui He ◽  
Ying Zhang
Keyword(s):  
Exercise Training ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Obese Mice ◽  
High Fat ◽  
Hypoxic Exercise

scholarly journals High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

2021 ◽  
Vol 22 (7) ◽  
pp. 3746
Author(s):  
Ilaria Zuliani ◽  
Chiara Lanzillotta ◽  
Antonella Tramutola ◽  
Eugenio Barone ◽  
Marzia Perluigi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Mitochondrial Activity ◽  
High Fat ◽  
Hexosamine Biosynthetic Pathway ◽  
Neurodegenerative Process ◽  
The Brain

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.

scholarly journals Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maki Murakoshi ◽  
Tomohito Gohda ◽  
Eri Adachi ◽  
Saki Ichikawa ◽  
Shinji Hagiwara ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Tubular Damage ◽  
Standard Diet ◽  
Mrna Levels ◽  
High Fat ◽  
Organ Specific

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Low Dose ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

scholarly journals Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

2017 ◽  
Vol 43 (5) ◽  
pp. 1961-1973 ◽  
Author(s):  
Yan Bai ◽  
Zhenli Su ◽  
Hanqi Sun ◽  
Wei Zhao ◽  
Xue Chen ◽  
...  
Keyword(s):  
Action Potential ◽  
Protein Expression ◽  
High Fat Diet ◽  
Qt Prolongation ◽  
Electrical Remodeling ◽  
High Fat ◽  
Treatment Groups ◽  
Aloe Emodin

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.

scholarly journals Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4548-4559 ◽  
Author(s):  
Mayumi Inoue ◽  
Yibin Jiang ◽  
Richard H. Barnes ◽  
Masakuni Tokunaga ◽  
Gabriel Martinez-Santibañez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Male Mice ◽  
High Fat ◽  
Adipose Tissues ◽  
Early Stages ◽  
Thrombospondin 1

Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression.

scholarly journals 7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet

2018 ◽  
Vol 120 (7) ◽  
pp. 751-762 ◽  
Author(s):  
Giorgio Biasiotto ◽  
Isabella Zanella ◽  
Federica Predolini ◽  
Ivonne Archetti ◽  
Moris Cadei ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
High Fat Diet ◽  
Sugar Metabolism ◽  
Lipid Uptake ◽  
High Fat ◽  
Total Extract ◽  
The Metabolic Syndrome ◽  
Metabolic Genes

Abstract7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the correspondingPicea abiesextract (total extractP. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (−11 and −13 %) and fat mass (−11 and −18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and −12 % smaller and the liver was less steatotic (−62 and −65 %). Serum lipids decreased in TEP-treated mice (−11 % cholesterol, −23 % LDL and −15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genesPPARγ,C/EBPαandaP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1–6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptakein vitro.

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