scholarly journals Hyperglycemia compromises the ischemia-provoked dedifferentiation of cerebral pericytes through p21–SOX2 signaling in high-fat diet-induced murine model

2021 ◽  
Vol 18 (1) ◽  
pp. 147916412199064
Author(s):  
Hao-Kuang Wang ◽  
Chih-Yuan Huang ◽  
Yun-Wen Chen ◽  
Yuan-Ting Sun
Keyword(s):  
High Fat Diet ◽  
Small Vessel Disease ◽  
Glucose Deprivation ◽  
Chow Group ◽  
Cellular Level ◽  
Neurological Deficits ◽  
High Fat ◽  
Diabetes Model ◽  
Patients With Diabetes ◽  
Sphere Formation

Aim: Diabetes-related cerebral small vessel disease (CSVD) causes neurological deficits. Patients with diabetes showed pericyte loss as a hallmark of retinopathy. Cerebral pericytes, which densely localize around brain capillaries, are quiescent stem cells regulating regeneration of brain and may have a role in CSVD development. This study investigated whether diabetes impairs ischemia-provoked dedifferentiation of pericytes. Methods: A murine high-fat diet (HFD)-induced diabetes model was used. After cerebral ischemia induction in the mice, pericytes were isolated and grown for a sphere formation assay. Results: The sphere counts from the HFD group were lower than those in the chow group. As the spheres formed, pericyte marker levels decreased and SOX2 levels increased gradually in the chow group, but not in the HFD group. Before sphere formation, pericytes from the HFD group showed high p21 levels. The use of a p21 inhibitor rescued the reduction of sphere counts in the HFD group. At cellular level, hyperglycemia-induced ROS increased the level of p21 in cerebral pericytes. The p21-SOX2 signaling was then activated after oxygen-glucose deprivation. Conclusion: HFD-induced diabetes compromises the stemness of cerebral pericytes by altering p21–SOX2 signaling. These results provide evidence supporting the role of pericytes in diabetes-related CSVD and subsequent cerebral dysfunction.

scholarly journals Role of TNF-α and FGF-2 in the Fracture Healing Disorder of Type 2 Diabetes Model Induced by High Fat Diet Followed by Streptozotocin

2020 ◽  
Vol Volume 13 ◽  
pp. 2279-2288
Author(s):  
Heqing Huang ◽  
Ling Luo ◽  
Zhitao Liu ◽  
Yan Li ◽  
Zhaochen Tong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fracture Healing ◽  
High Fat Diet ◽  
High Fat ◽  
Diabetes Model ◽  
Tnf Α

scholarly journals Novel mitochondrial complex I inhibitors restore glucose-handling abilities of high-fat fed mice

2016 ◽  
Vol 56 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Darren S D Martin ◽  
Siobhán Leonard ◽  
Robert Devine ◽  
Clara Redondo ◽  
Gemma K Kinsella ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
High Fat Diet ◽  
Complex I ◽  
Cellular Level ◽  
High Fat ◽  
Insulin Sensitizer ◽  
Kinase Activation ◽  
Drug Of Choice ◽  
Protein Kinase Activation ◽  
Complex I Activity

Metformin is the main drug of choice for treating type 2 diabetes, yet the therapeutic regimens and side effects of the compound are all undesirable and can lead to reduced compliance. The aim of this study was to elucidate the mechanism of action of two novel compounds which improved glucose handling and weight gain in mice on a high-fat diet. Wildtype C57Bl/6 male mice were fed on a high-fat diet and treated with novel, anti-diabetic compounds. Both compounds restored the glucose handling ability of these mice. At a cellular level, these compounds achieve this by inhibiting complex I activity in mitochondria, leading to AMP-activated protein kinase activation and subsequent increased glucose uptake by the cells, as measured in the mouse C2C12 muscle cell line. Based on the inhibition of NADH dehydrogenase (IC50 27µmolL−1), one of these compounds is close to a thousand fold more potent than metformin. There are no indications of off target effects. The compounds have the potential to have a greater anti-diabetic effect at a lower dose than metformin and may represent a new anti-diabetic compound class. The mechanism of action appears not to be as an insulin sensitizer but rather as an insulin substitute.

scholarly journals High fat diet-induced obesity prolongs critical stages of the spermatogenic cycle in a Ldlr−/−.Leiden mouse model

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
D. Komninos ◽  
L. Ramos ◽  
G. W. van der Heijden ◽  
M. C. Morrison ◽  
R. Kleemann ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Chromatin Condensation ◽  
Density Lipoprotein ◽  
Morphological Structure ◽  
High Plasma ◽  
Cellular Level ◽  
Seminiferous Tubules ◽  
High Fat ◽  
Knock Out ◽  
Sperm Dna Damage

AbstractObesity can disturb spermatogenesis and subsequently affect male fertility and reproduction. In our study, we aim to elucidate at which cellular level of adult spermatogenesis the detrimental effects of obesity manifest. We induced high fat diet (HFD) obesity in low-density lipoprotein receptor knock-out Leiden (Ldlr−/−.Leiden) mice, and studied the morphological structure of the testes and histologically examined the proportion of Sertoli cells, spermatocytes and spermatids in the seminiferous tubules. We examined sperm DNA damage and chromatin condensation and measured plasma levels of leptin, testosterone, cholesterol and triglycerides. HFD-induced obesity caused high plasma leptin and abnormal testosterone levels and induced an aberrant intra-tubular organisation (ITO) which is associated with an altered spermatids/spermatocytes ratio (2:1 instead of 3:1). Mice fed a HFD had a higher level of tubules in stages VII + VIII in the spermatogenic cycle. The stages VII + VII indicate crucial processes in spermatogenic development like initiation of meiosis, initiation of spermatid elongation, and release of fully matured spermatids. In conclusion, HFD-induced obese Ldlr−/−.Leiden mice develop an aberrant ITO and alterations in the spermatogenic cycle in crucial stages (stages VII and VII). Thereby, our findings stress the importance of lifestyle guidelines in infertility treatments.

High‐fat diet ameliorates neurological deficits caused by defective astrocyte lipid metabolism

2012 ◽  
Vol 26 (10) ◽  
pp. 4302-4315 ◽  
Author(s):  
Nutabi Camargo ◽  
Jos F. Brouwers ◽  
Maarten Loos ◽  
David H. Gutmann ◽  
August B. Smit ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Neurological Deficits ◽  
High Fat

scholarly journals An APJ agonist suppresses the loss of retinal neuronal cells in diabetes model mouse fed a high-fat diet

2020 ◽  
Vol 93 (0) ◽  
pp. 2-P-213
Author(s):  
Fumiya Shibagaki ◽  
Yuki Ishimaru ◽  
Kiichi Akai ◽  
Kana Tokuda ◽  
Akiko Yamamuro ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Neuronal Cells ◽  
High Fat ◽  
Diabetes Model ◽  
Model Mouse

scholarly journals Polyphenols-Rich Fruit (Euterpe edulis Mart.) Prevents Peripheral Inflammatory Pathway Activation by the Short-Term High-Fat Diet

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1655 ◽  
Author(s):  
Aline Boveto Santamarina ◽  
Giovana Jamar ◽  
Laís Vales Mennitti ◽  
Daniel Araki Ribeiro ◽  
Caroline Margonato Cardoso ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Chow Group ◽  
Control Group ◽  
High Fat ◽  
Inflammatory Pathway ◽  
Inflammatory Parameters ◽  
Pathway Activation ◽  
Freeze Dried

Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum access to food and water were divided into four experimental groups: control standard chow group (C); high-fat diet control group (HFC); high-fat diet juçara 0.25% group (HFJ0.25%); and high-fat diet juçara 0.5% group (HFJ0.5%). The inflammatory parameters were analyzed by ELISA and Western blotting in liver and retroperitoneal adipose tissue (RET). The HFJ0.25% group had the energy intake, aspartate transaminase (AST) levels, and liver triacylglycerol accumulation reduced; also, the tumor necrosis factor α (TNF-α) and TNF receptor-associated factor 6 (TRAF6) expression in RET were reduced. However, there were no changes in other protein expressions in liver and adipose tissue. Adiposity and pNFκBp50 had a positive correlation in HFC and HFJ0.5%, but not in the C group and HFJ0.25%. The necrosis hepatic score did not change with treatment; however, the serum (AST) levels and the hepatic triacylglycerol were increased in HFC and HFJ0.5%. These results demonstrated that one week of HFD intake triggered pro-inflammatory mechanisms and liver injury. Additionally, 0.25% juçara prevented inflammatory pathway activation, body weight gain, and liver damage

scholarly journals Long-chain non-coding RNA-GAS5 / hsa-miR-138-5p attenuates high glucose-induced cardiomyocyte damage by targeting CYP11B2

2021 ◽  
Author(s):  
Xiao-Zhen Zhuo ◽  
Kai Bai ◽  
Yingxian Wang ◽  
Peining Liu ◽  
Wen Xi ◽  
...  
Keyword(s):  
High Glucose ◽  
Myocardial Injury ◽  
Quantitative Polymerase Chain Reaction ◽  
Myocardial Damage ◽  
Cellular Level ◽  
Down Regulation ◽  
Non Coding Rna ◽  
Diabetes Model ◽  
Proliferation And Apoptosis ◽  
Patients With Diabetes

Objective: Diabetic cardiomyopathy (DCM) is one of the complications experienced by patients with diabetes. In recent years, long noncoding RNAs (lncRNAs) have been investigated because of their role in the progression of various diseases, including DCM. The purpose of this study was to explore the role of lncRNA GAS5 in high-glucose (HG)-induced cardiomyocyte injury and apoptosis. Materials and methods: We constructed HG-induced AC16 cardiomyocytes and a streptozotocin-induced rat diabetes model. GAS5 was overexpressed and knocked out at the cellular level, and GAS5 was knocked down by lentiviruses at the animal level to observe its effect on myocardial injury. Real-time quantitative polymerase chain reaction was used to detect the expression of GAS5. Cell proliferation and apoptosis after GAS5 knockout were detected by CCK-8, TUNEL, and flow cytometry assays. ELISA was used to detect the changes in myocardial enzyme content in cells and animal myocardial tissues during the action of GAS5 on myocardial injury. Results: GAS5 expression was up-regulated in HG-treated AC16 cardiomyocytes and the rat diabetic myocardial injury model. The down-regulation of GAS5 inhibited HG-induced myocardial damage. This work proved that GAS5 konckdown reversed cardiomyocyte injury and apoptosis by targeting miR-138 to down-regulate CYP11B2. Conclusion: We confirmed for the first time that the down-regulation of GAS5 could reverse CYP11B2 via the miR-138 axis to reverse HG-induced cardiomyocyte injury. This research might provide a new direction for explaining the developmental mechanism of DCM and potential targets for the treatment of myocardial injury.

Hydroxypropylated Tapioca Starch Retards the Development of Insulin Resistance in KKAy Mice, a Type 2 Diabetes Model, Fed a High-Fat Diet

2009 ◽  
Vol 74 (7) ◽  
pp. H232-H236 ◽  
Author(s):  
Makoto Tachibe ◽  
Ryo Kato ◽  
Shozo Sugano ◽  
Taro Kishida ◽  
Kiyoshi Ebihara
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
High Fat ◽  
Tapioca Starch ◽  
Kkay Mice ◽  
Diabetes Model
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