scholarly journals Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naho Kitamura ◽  
Yoko Yokoyama ◽  
Hiroki Taoka ◽  
Utana Nagano ◽  
Shotaro Hosoda ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Signaling Pathways ◽  
Hepatic Steatosis ◽  
Gene Transcription ◽  
High Fat Diet ◽  
Iron Supplementation ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
High Fat ◽  
Mitochondrial Signaling

AbstractDisruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.

scholarly journals The Edible Brown Seaweed Sargassum horneri (Turner) C. Agardh Ameliorates High-Fat Diet-Induced Obesity, Diabetes, and Hepatic Steatosis in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 551
Author(s):  
Shigeru Murakami ◽  
Chihiro Hirazawa ◽  
Takuma Ohya ◽  
Rina Yoshikawa ◽  
Toshiki Mizutani ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Weight Ratio ◽  
Brown Seaweed ◽  
Sargassum Horneri ◽  
Fecal Excretion ◽  
High Fat ◽  
Freeze Dried

Sargassum horneri (Turner) C. Agardh (S. horneri) is edible brown seaweed that grows along the coast of East Asia and has been traditionally used as a folk medicine and a local food. In this study, we evaluated the effects of S. horneri on the development of obesity and related metabolic disorders in C57BL/6J mice fed a high-fat diet. S. horneri was freeze-dried, fine-powdered, and mixed with a high-fat diet at a weight ratio of 2% or 6%. Feeding a high-fat diet to mice for 13 weeks induced obesity, diabetes, hepatic steatosis, and hypercholesterolemia. Supplementation of mice with S. horneri suppressed high-fat diet-induced body weight gain and the accumulation of fat in adipose tissue and liver, and the elevation of the serum glucose level. In addition, S. horneri improved insulin resistance. An analysis of the feces showed that S. horneri stimulated the fecal excretion of triglyceride, as well as increased the fecal polysaccharide content. Furthermore, extracts of S. horneri inhibited the activity of pancreatic lipase in vitro. These results showed that S. horneri can ameliorate diet-induced metabolic diseases, and the effect may be partly associated with the suppression of intestinal fat absorption.

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 Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Ishige okamurae Extract Suppresses Obesity and Hepatic Steatosis in High Fat Diet-Induced Obese Mice

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1802 ◽  
Author(s):  
Young-Jin Seo ◽  
Kippeum Lee ◽  
Ji-Hyeon Song ◽  
Sungwoo Chei ◽  
Boo-Yong Lee
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
Binding Protein ◽  
Regulatory Element ◽  
Hormone Sensitive Lipase ◽  
High Fat ◽  
Ishige Okamurae

Obesity is caused by the expansion of white adipose tissue (WAT), which stores excess triacylglycerol (TG), this can lead to disorders including type 2 diabetes, atherosclerosis, metabolic diseases. Ishige okamurae extract (IOE) is prepared from a brown alga and has anti-oxidative properties. We investigated the detailed mechanisms of the anti-obesity activity of IOE. Treatment with IOE blocked lipid accumulation by reducing expression of key adipogenic transcription factors, such as CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), in 3T3-L1 cells. Administration of IOE to high fat diet (HFD)-fed mice inhibited body and WAT mass gain, attenuated fasting hyperglycemia and dyslipidemia. The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. In summary, IOE ameliorates HFD-induced obesity and its related metabolic disease, hepatic steatosis, by regulating multiple pathways.

scholarly journals Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis

2009 ◽  
Vol 297 (6) ◽  
pp. E1420-E1429 ◽  
Author(s):  
Frederic Preitner ◽  
Nimesh Mody ◽  
Timothy E. Graham ◽  
Odile D. Peroni ◽  
Barbara B. Kahn
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Retinol Binding Protein ◽  
Term Therapy ◽  
High Fat ◽  
Diet Induced Obesity

The synthetic retinoid Fenretinide (FEN) increases insulin sensitivity in obese rodents and is in early clinical trials for treatment of insulin resistance in obese humans with hepatic steatosis (46). We aimed to determine the physiological mechanisms for the insulin-sensitizing effects of FEN. Wild-type mice were fed a high-fat diet (HFD) with or without FEN from 4–5 wk to 36–37 wk of age (preventive study) or following 22 wk of HF diet-induced obesity (12 wk intervention study). Retinol-binding protein-4 (RBP4) knockout mice were also fed the HFD with or without FEN in a preventive study. FEN had minimal effects on HFD-induced body weight gain but markedly reduced HFD-induced adiposity and hyperleptinemia in both studies. FEN-HFD mice gained epididymal fat but not subcutaneous or visceral fat mass in contrast to HFD mice without FEN. FEN did not have a measurable effect on energy expenditure, food intake, physical activity, or stool lipid content. Glucose infusion rate during hyperinsulinemic-euglycemic clamp was reduced 86% in HFD mice compared with controls and was improved 3.6-fold in FEN-HFD compared with HFD mice. FEN improved insulin action on glucose uptake and glycogen levels in muscle, insulin-stimulated suppression of hepatic glucose production, and suppression of serum FFA levels in HFD mice. Remarkably, FEN also reduced hepatic steatosis. In RBP4 knockout mice, FEN reduced the HFD-induced increase in adiposity and hyperleptinemia. In conclusion, long-term therapy with FEN partially prevents or reverses obesity, insulin resistance, and hepatic steatosis in mice on HFD. The anti-adiposity effects are independent of the RBP4 lowering effect.

scholarly journals Helminthostachys zeylanica alleviates hepatic steatosis and insulin resistance in diet-induced obese mice

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ting-Chen Chang ◽  
Hao Chiang ◽  
Yu-Heng Lai ◽  
Yu-Ling Huang ◽  
Hsiu-Chen Huang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Tissue Expansion ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Helminthostachys Zeylanica

Abstract Background Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling. Methods Helminthostachys zeylanica (HZ) is used widely as a common herbal medicine to relieve fever symptoms and inflammatory diseases in Asia. In the present study, we evaluated whether HZ has therapeutic effects on obesity, NAFLD and insulin resistance. The protective effects of HZ extract were examined using free fatty acid-induced steatosis in human HuS-E/2 cells and a high-fat diet-induced NAFLD in mice. Results The major components of the HZ extract are ugonins J and K, confirmed by HPLC. Incubation of human hepatocytes, HuS-E/2 cells, with palmitate markedly increased lipid accumulation and treatment with the HZ extract significantly decreased lipid deposition and facilitated AMPK and ACC activation. After 12 weeks of a high-fat diet with HZ extract treatment, the HFD mice were protected from hyperlipidemia and hyperglycemia. HZ extract prevented body weight gain, adipose tissue expansion and adipocyte hypertrophy in the HFD mice. In addition, fat accumulation was reduced in mice livers. Moreover, the insulin sensitivity-associated index, which evaluates insulin function, was also significantly restored. Conclusions These results suggest that HZ has a promising pharmacological effect on high-fat diet-induced obesity, hepatic steatosis and insulin resistance, which may have the potential for clinical application.

scholarly journals Combination Treatment of Arazyme and Soy Leaf Extract Attenuates Hyperglycemia and Hepatic Steatosis in High-Fat Diet-Fed C57BL/6J Mice

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 645
Author(s):  
Hwa Lee ◽  
Seona Cho ◽  
Anna Kang ◽  
Dong-Ha Shin ◽  
Ho-Yong Park ◽  
...  
Keyword(s):  
Body Weight ◽  
Bile Acid ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Lipid Synthesis ◽  
Therapeutic Effects ◽  
High Fat ◽  
Insulin Tolerance ◽  
Bile Acid Transporter

Arazyme and extracts of soy leaves (ESLs) are used as ingredients for functional foods; however, their combined administration has not been studied. This study assessed the combined effect of Arazyme and ESLs in high-fat-diet (HFD)-induced obese C57BL/6J mice fed 2 mg/kg Arazyme, 50 mg/kg ESLs, or a combination of 2 mg/kg Arazyme and 50 mg/kg ESLs by oral gavage for 13 weeks. Individually, Arazyme and ESLs had no effect on the HFD-induced phenotypes. The combination of Arazyme and ESLs significantly suppressed body weight gain, improved glucose and insulin tolerance, and suppressed hepatic steatosis by reducing lipid synthesis and enhancing lipid utilization gene expression. Furthermore, the combination significantly reduced HFD-induced plasma bile acid reabsorption by suppressing bile acid transporter expression, including the ATP biding cassette subfamily B member 11 (Abcb11), solute carrier family 10 member 1 (Slc10a1), Slc10a2, Slc51a, and Slc51b in the liver and gut. Moreover, the combination of Arazyme and ESLs significantly prevented HFD-induced islet compensation in the pancreas. These results suggest that the incorporation of Arazyme combined with ESLs reduces HFD-induced body weight, hyperglycemia, and hepatic steatosis by regulating liver–gut bile acid circulation in HFD-fed mice. This combination can markedly reduce treatment doses and enhance their therapeutic effects, thereby reducing therapeutic healthcare costs.

scholarly journals Murine Genetic Background Overcomes Gut Microbiota Changes to Explain Metabolic Response to High-Fat Diet

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 287 ◽  
Author(s):  
Zahra Safari ◽  
Aurélia Bruneau ◽  
Magali Monnoye ◽  
Mahendra Mariadassou ◽  
Catherine Philippe ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Genetic Background ◽  
Metabolic Diseases ◽  
Metabolic Response ◽  
Body Weight Gain ◽  
Mouse Strains ◽  
Donor Strain ◽  
High Fat ◽  
Microbiome Composition

Interactions of diet, gut microbiota, and host genetics play essential roles in the development of metabolic diseases. A/J and C57BL/6J (C57) are two mouse strains known to display different susceptibilities to metabolic disorders. In this context, we analyzed gut microbiota composition in A/J and C57 mice, and assessed its responses to high-fat diet (HFD) and antibiotic (AB) treatment. We also exchanged the gut microbiota between the two strains following AB treatment to evaluate its impact on the metabolism. We showed that A/J and C57 mice have different microbiome structure and composition at baseline. Moreover, A/J and C57 microbiomes responded differently to HFD and AB treatments. Exchange of the gut microbiota between the two strains was successful as recipients’ microbiota resembled donor-strain microbiota. Seven weeks after inoculation, the differences between recipients persisted and were still closer from the donor-strain microbiota. Despite effective microbiota transplants, the response to HFD was not markedly modified in C57 and A/J mice. Particularly, body weight gain and glucose intolerance in response to HFD remained different in the two mouse strains whatever the changes in microbiome composition. This indicated that genetic background has a much stronger impact on metabolic responses to HFD than gut microbiome composition.

Offspring of high fat diet fed dams develop hepatic steatosis

2014 ◽  
Vol 52 (01) ◽  
Author(s):  
JP Sowa ◽  
L Wingerter ◽  
G Gerken ◽  
M Palmert ◽  
A Canbay ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
High Fat
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