scholarly journals Macrophage‐specific hypoxia‐inducible factor‐1α deletion suppresses the development of liver tumors in high‐fat diet‐fed obese and diabetic mice

2019 ◽  
Vol 10 (6) ◽  
pp. 1411-1418
Author(s):  
Akiko Takikawa ◽  
Isao Usui ◽  
Shiho Fujisaka ◽  
Koichi Tsuneyama ◽  
Keisuke Okabe ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Liver Tumors ◽  
Hypoxia Inducible Factor ◽  
Diabetic Mice ◽  
High Fat ◽  
Hypoxia Inducible Factor 1Α

Cardiovascular disease is associated with high-fat-diet-induced liver damage and up-regulation of the hepatic expression of hypoxia-inducible factor 1α in a rat model

2012 ◽  
Vol 124 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Adriana L. Burgueño ◽  
Tomas F. Gianotti ◽  
Noelia G. Mansilla ◽  
Carlos J. Pirola ◽  
Silvia Sookoian
Keyword(s):  
Cardiovascular Disease ◽  
Liver Damage ◽  
High Fat Diet ◽  
Liver Enzymes ◽  
Hypoxia Inducible Factor ◽  
Sirtuin 1 ◽  
Chow Diet ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Hypoxia Inducible Factor 1Α

CVD (cardiovascular disease) is associated with abnormal liver enzymes, and NAFLD (non-alcoholic fatty liver disease) is independently associated with cardiovascular risk. To gain insights into the molecular events underlying the association between liver enzymes and CVD, we developed an HFD (high-fat diet)-induced NAFLD in the SHR (spontaneously hypertensive rat) and its control WKY (Wistar–Kyoto) rat strain. We hypothesized that hepatic induction of Hif1a (hypoxia-inducible factor 1α) might be the link between CVD and liver injury. Male SHRs (n=13) and WKY rats (n=14) at 16 weeks of age were divided into two experimental groups: standard chow diet and HFD (10 weeks). HFD-fed rats, irrespective of the strain, developed NAFLD; however, only HFD-SHRs had focus of lobular inflammation and high levels of hepatic TNFα (tumour necrosis factor α). SHRs had significantly higher liver weight and ALT (alanine aminotransferase) levels, irrespective of NAFLD. Liver abundance of Hif1a mRNA and Hif1α protein were overexpressed in SHRs (P<0.04) and were significantly correlated with ALT levels (R=0.50, P<0.006). This effect was not reverted by a direct acting splanchnic vasodilator (hydralazine). Angiogenesis may be induced by the HFD, but the disease model showed significantly higher hepatic Vegf (vascular endothelial growth factor) levels (P<0.025) even in absence of dietary insult. Hif1a mRNA overexpression was not observed in other tissues. Liver mRNA of Nr1d1 (nuclear receptor subfamily 1, group D, member 1; P<0.04), Ppara [Ppar (peroxisome-proliferatoractivated receptor) α; P<0.05], Pparg (Pparγ; P<0.001) and Sirt1 (Sirtuin 1; P<0.001) were significantly upregulated in SHRs, irrespective of NAFLD. Sirt1 and Hif1a mRNAs were significantly correlated (R=0.71, P<0.00002). In conclusion, CVD is associated with Hif1a-related liver damage, hepatomegaly and reprogramming of liver metabolism, probably to compensate metabolic demands.

scholarly journals Hepatocellular Carcinoma Emergence in Diabetic Mice with Non-Alcoholic Steatohepatitis Depends on Diet and Is Delayed in Liver Exhibiting an Active Immune Response

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1491
Author(s):  
Mélanie Simoes Eugénio ◽  
Muhammad Farooq ◽  
Sarah Dion ◽  
Christelle Devisme ◽  
Céline Raguenes-Nicol ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
High Fat Diet ◽  
Liver Tumors ◽  
High Cholesterol Diet ◽  
Diabetic Mice ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
The Impact

The increase of the sedentary lifestyle and high-calorie diet have modified the etiological landscape of hepatocellular carcinoma (HCC), with a recrudescence of non-alcoholic fatty liver disease (NAFLD), especially in Western countries. The purpose of our study was to evaluate the impact of high-fat diet feeding on non-alcoholic steatohepatitis (NASH) establishment and HCC development. Streptozotocin-induced diabetic male mice were fed with high-fat-high-cholesterol diet (HFHCD) or high-fat-high-sugar diet (HFHSD) from 1 to 16 weeks. Even if liver tumors appear regardless of the high-fat diet, two distinct physiopathological patterns were evidenced, with much more severe NASH hallmarks (liver injury, inflammation and fibrosis) in diabetic mice fed with HFHCD. The mild hepatic injury, weak inflammation and fibrosis observed in HFHSD were interestingly associated with earlier emergence of more numerous liver tumors. When activated helper and cytotoxic T cells, detected by flow cytometry, infiltrated the liver of HFHCD-fed diabetic mice, a delay in the appearance of tumor nodules and a limitation of their numbers were observed, suggesting that the immune activities partly controlled tumor emergence. These data highlighted two different mouse models of HCC progression in diabetic mice depending on diet, which could be useful to evaluate new therapeutic approaches for HCC by targeting the immune response.

scholarly journals Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin expression in diabetic mice on a high-fat diet

2017 ◽  
Vol 33 (7) ◽  
pp. 321-326 ◽  
Author(s):  
Fang-Hua Gong ◽  
Yan-Na Ye ◽  
Jin-Meng Li ◽  
Hai-Yang Zhao ◽  
Xiao-Kun Li
Keyword(s):  
High Fat Diet ◽  
Diabetic Mice ◽  
High Fat

Hypoglycemic effects of Auricularia auricula polysaccharides on high fat diet and streptozotocin-induced diabetic mice using metabolomics analysis

2021 ◽  
Author(s):  
nannan liu ◽  
Xuefeng Chen ◽  
Juanna Song ◽  
Mengyin Chen ◽  
Pin Gong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
Male Mice ◽  
High Fat ◽  
Auricularia Auricula ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Metabolomic Approach ◽  
Metabolomics Analysis

This study evaluated the hypoglycemic effect of Auricularia auricula polysaccharides (AAPs) on streptozotocin-induced type 2 diabetes mellitus (T2DM) male mice (C57BL/6J) using a metabolomic approach based on ultrahigh-performance liquid chromatography–Q...

FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice

2022 ◽  
Author(s):  
Somayeh Aslani ◽  
Saman Bahrambeigi ◽  
Davoud Sanajou
Keyword(s):  
Liver Injury ◽  
High Fat Diet ◽  
Lifestyle Modification ◽  
Serum Levels ◽  
Diabetic Mice ◽  
High Fat ◽  
Lifestyle Modifications ◽  
Gamma Glutamyl Transpeptidase ◽  
Alcoholic Fatty Liver

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.

scholarly journals Therapeutic effects of Hypoxia-Inducible Factor-1α (HIF-1α) on bone formation around implants in diabetic mice

2018 ◽  
Author(s):  
Sang-Min Oh ◽  
Jin-Su Shin ◽  
Il-Koo Kim ◽  
Jae-Seung Moon ◽  
Jung-Ho Kim ◽  
...  
Keyword(s):  
Bone Formation ◽  
Rna Sequencing ◽  
Normal Mouse ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Diabetic Mouse ◽  
Differentially Expressed ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Hypoxia Inducible Factor 1Α

AbstractPatients with uncontrolled diabetes are susceptible to implant failure due to impaired bone metabolism. Hypoxia-Inducible Factor 1α (HIF-1α), a transcription factor that is up-regulated in response to reduced oxygen condition during the bone repair process after fracture or osteotomy, is known to mediate angiogenesis and osteogenesis. However, its function is inhibited under hyperglycemic conditions in diabetic patients. The aim of this study is to evaluate the effects of exogenous HIF-1α on bone formation around implants by applying HIF-1α to diabetic mice via a novel PTD-mediated DNA delivery system. Smooth surface implants (1mm in diameter; 2mm in length) were placed in the both femurs of diabetic and normal mice. HIF-1α and placebo gels were injected to implant sites of the right and left femurs, respectively: Normal mouse with HIF-1α gel (NH), Normal mouse with placebo gel (NP), Diabetic mouse with HIF-1α gel (DH), and Diabetic mouse with placebo gel (DP). RNA sequencing was performed 4 days after surgery. Based on RNA sequencing, Differentially Expressed Genes (DEGs) were identified and HIF-1α target genes were selected. Histologic and histomorphometric results were evaluated 2 weeks after the surgery. The results showed that bone-to-implant contact (BIC) and bone volume (BV) were significantly greater in the DH group than the DP group (p < 0.05). A total of 216 genes were differentially expressed in DH group compared to DP group. On the other hand, there were 95 DEGs in the case of normal mice. Twenty-one target genes of HIF-1α were identified in diabetic mice through bioinformatic analysis of DEGs. Among the target genes, NOS2, GPNMB, CCL2, CCL5, CXCL16 and TRIM63 were manually found to be associated with wound healing-related genes. In conclusion, local administration of HIF-1α via PTD may help bone formation around the implant and induce gene expression more favorable to bone formation in diabetic mice.

Intake of Flavonoids from Astragalus Membranaceus Ameliorated Brain Impairment in Diabetic Mice Via Modulating Brain-Gut Axis

2021 ◽  
Author(s):  
Li Xuling ◽  
Junling Gu ◽  
Zhe Wang ◽  
Jing Lin ◽  
Tingting Zhao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Brain Damage ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Synaptic Function ◽  
Astragalus Membranaceus ◽  
Immunological Methods ◽  
Diabetic Mice ◽  
High Fat

Abstract Background: Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown.Methods: Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC-MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. Results: We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. Conclusion: Our findings demonstrated that flavonoids from Astragalus Membranaceus ameliorated brain impairment via gut-brain axis. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.

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