scholarly journals Sesamol Increases Ucp1 Expression in White Adipose Tissues and Stimulates Energy Expenditure in High-Fat Diet-Fed Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1459 ◽  
Author(s):  
Dong Ho Lee ◽  
Seo-Hyuk Chang ◽  
Dong Kwon Yang ◽  
No-Joon Song ◽  
Ui Jeong Yun ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
The Body ◽  
High Fat ◽  
Adipose Tissues ◽  
Ucp1 Expression ◽  
Nrf2 Activator

Sesamol found in sesame oil has been shown to ameliorate obesity by regulating lipid metabolism. However, its effects on energy expenditure and the underlying molecular mechanism have not been clearly elucidated. In this study, we show that sesamol increased the uncoupling protein 1 (Ucp1) expression in adipocytes. The administration of sesamol in high-fat diet (HFD)-fed mice prevented weight gain and improved metabolic derangements. The three-week sesamol treatment of HFD-fed mice, when the body weights were not different between the sesamol and control groups, increased energy expenditure, suggesting that an induced energy expenditure is a primary contributing factor for sesamol’s anti-obese effects. Consistently, sesamol induced the expression of energy-dissipating thermogenic genes, including Ucp1, in white adipose tissues. The microarray analysis showed that sesamol dramatically increased the Nrf2 target genes such as Hmox1 and Atf3 in adipocytes. Moreover, 76% (60/79 genes) of the sesamol-induced genes were also regulated by tert-butylhydroquinone (tBHQ), a known Nrf2 activator. We further verified that sesamol directly activated the Nrf2-mediated transcription. In addition, the Hmox1 and Ucp1 induction by sesamol was compromised in Nrf2-deleted cells, indicating the necessity of Nrf2 in the sesamol-mediated Ucp1 induction. Together, these findings demonstrate the effects of sesamol in inducing Ucp1 and in increasing energy expenditure, further highlighting the use of the Nrf2 activation in stimulating thermogenic adipocytes and in increasing energy expenditure in obesity and its related metabolic diseases.

scholarly journals Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

2021 ◽  
Author(s):  
Won-Il Choi ◽  
Jae-Hyun Yoon ◽  
Seo-Hyun Choi ◽  
Bu-Nam Jeon ◽  
Hail Kim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Target Genes ◽  
Proximal Promoter ◽  
High Fat ◽  
Tissue Mass ◽  
Adipose Tissues ◽  
Adipose Tissue Mass ◽  
Age Dependent ◽  
Treatment Of Diabetes

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

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.

Abstract 394: Posttranslational Modification Of Klf5 Mediates Metabolic Dysfunction And Vascular Disease In Metabolic Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yumiko Oishi ◽  
Ichiro Manabe ◽  
Kazuyuki Tobe ◽  
Takashi Kadowaki ◽  
Ryozo Nagai
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Energy Expenditure ◽  
Posttranslational Modifications ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
C2c12 Myotubes ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Increased Risk

We have previously shown that a zinc finger transcription factor, Krüppel-like factor 5 (KLF5), plays an important role in pathogenesis of cardiovascular diseases, such as atherosclerosis. KLF5 heterozygous knockout ( KLF5 +/ − ) mice exhibited much less neointima formation, cardiac hypertrophy and fibrosis. We also found that expression of KLF5 correlated with a higher incidence of restenosis following PCI and the SNP located within the KLF5 promoter was associated with an increased risk of hypertension in man. Interestingly, KLF5 is also expressed in metabolic tissues such as adipose tissue, skeletal muscle, and pancreatic β-cells. Thus, we hypothesized that KLF5 might play a role in metabolic diseases. To test this, KLF5 +/ − mice were fed with high-fat diet. Although KLF5 +/ − mice ate more food than wild-type littermates, they were resistant to high-fat diet-induced obesity and protected from dyslipidemia, glucose intolerance and hepatic steatosis, indicating that KLF5 + /− mice were less susceptible to metabolic syndrome. The systemic O 2 consumption and expression of genes involved in energy expenditure in skeletal muscle were increased in KLF5 + /− mice, demonstrating enhanced energy expenditure, which partly explains the phenotype. Knocking down KLF5 by siRNA increased expression levels of UCP2/3 and CPT-1b in C2C12 myotubes, suggesting that KLF5 may inhibit energy expenditure-related genes. Chromatin immunoprecipitation and coimmunoprecipitation assays showed that KLF5 interacted with corepressors, such as SMRT and NCoR, and strongly inhibited the UCP and CPT-1b promoters. We found that this inhibitory activity of KLF5 depended on its SUMOylation. When KLF5 was deSUMOylated, it activated the promoters. These data demonstrate that KLF5 acts as a molecular switch for energy expenditure and the posttranslational modifications of KLF5 including SUMOylation turns on/off the switch function of KLF5. Given that KLF5 also controls tissue remodeling in response to external stress, KLF5 may mediate metabolic dysfunction and atherosclerosis in metabolic syndrome. Our findings also suggest that the posttranscriptional modification of KLF5 is an attractive novel therapeutic target.

scholarly journals Kappa-Carrageenan Inhibited the High-Fat-Diet-Induced Obesity Through Up-Regulating the Hepatic Sirt1 Gene Expression

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 503-503
Author(s):  
Zhiji Huang ◽  
Yafang Ma ◽  
Chunbao Li
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Energy Intake ◽  
High Fat Diet ◽  
The Body ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Sirt1 Gene ◽  
Kappa Carrageenan

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake.  The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)

scholarly journals AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1457-1466 ◽  
Author(s):  
Miyuki Shibata ◽  
Ryoichi Banno ◽  
Mariko Sugiyama ◽  
Takashi Tominaga ◽  
Takeshi Onoue ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucocorticoid Receptor ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
Chow Diet ◽  
Wild Type ◽  
High Fat ◽  
Brown Adipose

Abstract Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

scholarly journals Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 26 ◽  
Author(s):  
Jin Choi ◽  
No-Joon Song ◽  
A Lee ◽  
Dong Lee ◽  
Min-Ju Seo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Obese Mice ◽  
High Fat ◽  
White Adipocyte

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.

scholarly journals Effect of high-fat diet on secreted milk transcriptome in midlactation mice

2017 ◽  
Vol 49 (12) ◽  
pp. 747-762 ◽  
Author(s):  
Y. Chen ◽  
J. Wang ◽  
S. Yang ◽  
S. Utturkar ◽  
J. Crodian ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Milk Fat ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Control Diet ◽  
Milk Composition ◽  
High Fat ◽  
Enriched Categories ◽  
Mrna Content ◽  
Organismal Development

High-fat diet (HFD) during lactation alters milk composition and is associated with development of metabolic diseases in the offspring. We hypothesized that HFD affects milk microRNA (miRNA) and mRNA content, which potentially impact offspring development. Our objective was to determine the effect of maternal HFD on secreted milk transcriptome. To meet this objective, 4 wk old female ICR mice were divided into two treatments: control diet containing 10% kcal fat and HFD containing 60% kcal fat. After 4 wk on CD or HFD, mice were bred while continuously fed the same diets. On postnatal day 2 (P2), litters were normalized to 10 pups, and half the pups in each litter were cross-fostered between treatments. Milk was collected from dams on P10 and P12. Total RNA was isolated from milk fat fraction of P10 samples and used for mRNA-Seq and small RNA-Seq. P12 milk was used to determine macronutrient composition. After 4 wk of prepregnancy feeding HFD mice weighed significantly more than did the control mice. Lactose and fat concentration were significantly ( P < 0.05) higher in milk of HFD dams. Pup weight was significantly greater ( P < 0.05) in groups suckled by HFD vs. control dams. There were 25 miRNA and over 1,500 mRNA differentially expressed (DE) in milk of HFD vs. control dams. DE mRNA and target genes of DE miRNA enriched categories that were primarily related to multicellular organismal development. Maternal HFD impacts mRNA and miRNA content of milk, if bioactive nucleic acids are absorbed by neonate differences may affect development.

scholarly journals Bardoxolone Methyl Prevents Mesenteric Fat Deposition and Inflammation in High-Fat Diet Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Chi H. L. Dinh ◽  
Alexander Szabo ◽  
Yinghua Yu ◽  
Danielle Camer ◽  
Hongqin Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
Fat Deposition ◽  
Therapeutic Effects ◽  
Stress Effect ◽  
High Fat ◽  
Mesenteric Adipose Tissue ◽  
Mesenteric Fat

Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue.

scholarly journals Choline-deficient High-fat Diet-induced Steatohepatitis in BALB/c Mice

2021 ◽  
Vol 5 (2) ◽  
pp. 74
Author(s):  
Saut Horas Hatoguan Nababan ◽  
Seruni Tyas Khairunissa ◽  
Erni Erfan ◽  
Nafrialdi Nafrialdi ◽  
Ening Krisnuhoni ◽  
...  
Keyword(s):  
Fatty Acids ◽  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Uncoupling Protein ◽  
Saturated Fatty Acids ◽  
The Body ◽  
Standard Diet ◽  
High Fat ◽  
Expression Levels ◽  
Relative Expression

Background: Non-alcoholic steatohepatitis (NASH) is an expanding cause of chronic liver disease worldwide, including Indonesia, with higher risk progression to cirrhosis and hepatocellular carcinoma. Preclinical experiments using several mice models have been conducted to clarify its complex pathogenesis. This study was designed to investigate whether BALB/c mice on a choline-deficient high-fat diet can be used as a model for NASH. Materials and Methods: BALB/c male mice were fed choline-deficient L-amino acid-defined high-fat diet (CDAHFD) or a standard diet for six weeks. The body and liver weights, liver histology, and plasma biochemistry were analyzed. The relative expression levels of tumor necrosis factor (TNF)α, transforming growth factor (TGF)β1, collagen-1α1 (COL1α1), glutathione peroxidase 1 (GPx1), and uncoupling protein 2 (UCP2) genes in the livers were analyzed using a two-step real time-polymerase chain reaction. Liver fatty acids composition was analyzed using gas chromatography with flame ionization detector (GC-FID). Results: CDAHFD induced steatohepatitis in BALB/c mice with increased plasma levels of alanine aminotransferase. The liver of CDAHFD-fed BALB/c mice showed upregulated relative expression levels of TNFα, TGFβ1, COL1α1, GPx1, and UCP2 genes. The liver fatty acid analysis showed a significant accumulation of saturated fatty acids (SFAs) and an increased ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) in the livers of CDAHFD-fed BALB/c mice. Conclusion: This study suggests that CDAHFD can induce steatohepatitis in BALB/c mice and therefore may be used as NASH mice model.Keywords: steatohepatitis, fatty liver, choline-deficient high fat diet, BALB/c 

scholarly journals Effects of Methanolic Leaf Extract of Clinacanthus nutans on Fatty Acid Composition and Gene Expression in Male Obese Mice

2018 ◽  
Author(s):  
Samiaa Jamil Abdulwahid ◽  
Meng Yong Goh ◽  
Mahdi Ebrahimi ◽  
Norhafizah Mohtarrudin ◽  
Zailina Binti Hashim
Keyword(s):  
Fatty Acid ◽  
High Fat Diet ◽  
Leaf Extract ◽  
Metabolic Diseases ◽  
The Body ◽  
Health Concern ◽  
Obese Mice ◽  
High Fat ◽  
Wide Range ◽  
Clinacanthus Nutans

Obesity is a universal health concern that can lead to serious diseases. The side effects of synthetic anti-obesity drugs necessitate the finding of suitable natural/herbal alternatives. Mother nature offers a wide range of plants with medicinal properties that include crude extracts and isolated compounds which are effective for controlling and reducing weight gain. Obesity was induced in 60, 3-week-old male ICR mice, using high-fat diet (60% dietary energy from fat) for 16-week. The mice were divided at random into six groups with 10 mice: mice fed with high-fat diet (HFD) only, mice fed normal diet only (NC), and orlistat at 15.9 mg/kg (HFD+Orlistat), and mice in three other high-fat diet groups treated with methanolic leaf extract of Clinacanthus nutans (MECN) at 500, 1000 and 1500 mg/kg. After 21-day of the treatment, MECN significantly reduced (P&lt;0.05) the body weight, visceral fat and muscle saturated fatty acid compositions. There was also significant downregulation of HSL, PPAR &alpha; and PPAR &gamma; and SCD genes expressions in the obese mice treated with 1500 mg/kg MECN compared to the HFD group. Therefore, MECN is a potentially useful natural supplement for alleviating obesity and obesity-mediated metabolic diseases.

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