Induction and rescue of skeletal fragility in a high-fat diet mouse model of type 2 diabetes: An in vivo and in vitro approach

Bone ◽  
2021 ◽  
pp. 116302
Author(s):  
Joan E. LLabre ◽  
Grażyna E. Sroga ◽  
Matthew J.L. Tice ◽  
Deepak Vashishth
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
High Fat Diet ◽  
High Fat ◽  
Skeletal Fragility

scholarly journals TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet fed mouse

2018 ◽  
Vol 132 (1) ◽  
pp. 69-83 ◽  
Author(s):  
Stella Bernardi ◽  
Barbara Toffoli ◽  
Veronica Tisato ◽  
Fleur Bossi ◽  
Stefania Biffi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
High Fat Diet ◽  
Disease Onset ◽  
High Fat ◽  
Primary Hepatocytes

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. The present study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD). After 4 weeks of HFD, mice were further randomized to receive either placebo or TRAIL, which was delivered weekly for 8 weeks. Body weight, food intake, fasting glucose, and insulin were measured at baseline and every 4 weeks. Tolerance tests were performed before drug randomization and at the end of the study. Tissues were collected for further analyses. Parallel in vitro studies were conducted on HepG2 cells and mouse primary hepatocytes. TRAIL significantly reduced body weight, adipocyte hypertrophy, free fatty acid levels, and inflammation. Moreover, it significantly improved impaired glucose tolerance, and ameliorated non-alcoholic fatty liver disease (NAFLD). TRAIL treatment reduced liver fat content by 47% in vivo as well as by 45% in HepG2 cells and by 39% in primary hepatocytes. This was associated with a significant increase in liver peroxisome proliferator-activated receptor (PPAR) γ (PPARγ) co-activator-1 α (PGC-1α) expression both in vivo and in vitro, pointing to a direct protective effect of TRAIL on the liver. The present study confirms the ability of TRAIL to significantly attenuate diet-induced metabolic abnormalities, and it shows for the first time that TRAIL is effective also when administered after disease onset. In addition, our data shed light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD.

scholarly journals Antiobesity Effects of Gentiana lutea Extract on 3T3-L1 Preadipocytes and a High-Fat Diet-Induced Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2453 ◽  
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Junho Kim ◽  
Subin Yeo ◽  
Ji Ae Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Metabolic Diseases ◽  
Obese Mouse ◽  
High Fat ◽  
Messenger Ribonucleic Acid ◽  
Gentiana Lutea

Obesity is one of the most common metabolic diseases resulting in metabolic syndrome. In this study, we investigated the antiobesity effect of Gentiana lutea L. (GL) extract on 3T3-L1 preadipocytes and a high-fat-diet (HFD)-induced mouse model. For the induction of preadipocytes into adipocytes, 3T3-L1 cells were induced by treatment with 0.5 mM 3-isobutyl-1-methylxanthine, 1 mM dexamethasone, and 1 μg/mL insulin. Adipogenesis was assessed based on the messenger ribonucleic acid expression of adipogenic-inducing genes (adiponectin (Adipoq), CCAAT/enhancer-binding protein alpha (Cebpa), and glucose transporter type 4 (Slc2a4)) and lipid accumulation in the differentiated adipocytes was visualized by Oil Red O staining. In vivo, obese mice were induced with HFD and coadministered with 100 or 200 mg/kg/day of GL extract for 12 weeks. GL extract treatment inhibited adipocyte differentiation by downregulating the expression of adipogenic-related genes in 3T3-L1 cells. In the obese mouse model, GL extract prevented HFD-induced weight gain, fatty hepatocyte deposition, and adipocyte size by decreasing the secretion of leptin and insulin. In conclusion, GL extract shows antiobesity effects in vitro and in vivo, suggesting that this extract can be beneficial in the prevention of obesity.

scholarly journals The Antiinflammatory Cytokine Interleukin-1 Receptor Antagonist Protects from High-Fat Diet-Induced Hyperglycemia

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2208-2218 ◽  
Author(s):  
Nadine S. Sauter ◽  
Fabienne T. Schulthess ◽  
Ryan Galasso ◽  
Lawrence W. Castellani ◽  
Kathrin Maedler
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Receptor Antagonist ◽  
High Fat Diet ◽  
Cell Function ◽  
Interleukin 1 ◽  
High Fat ◽  
Β Cell

Subclinical inflammation is a recently discovered phenomenon in type 2 diabetes. Elevated cytokines impair β-cell function and survival. A recent clinical trial shows that blocking IL-1β signaling by IL-1 receptor antagonist (IL-1Ra) improves β-cell secretory function in patients with type 2 diabetes. In the present study, we provide further mechanisms of the protective role of IL-1Ra on the β-cell. IL-1Ra prevented diabetes in vivo in C57BL/6J mice fed a high-fat/high-sucrose diet (HFD) for 12 wk; it improved glucose tolerance and insulin secretion. High-fat diet treatment increased serum levels of free fatty acids and of the adipokines resistin and leptin, which were reduced by IL-1Ra treatment. In addition, IL-1Ra counteracted adiponectin levels, which were decreased by high-fat feeding. Studies on isolated islets revealed that IL-1Ra specifically acted on the β-cell. IL-1Ra protected islets from HFD treated animals from β-cell apoptosis, induced β-cell proliferation, and improved glucose-stimulated insulin secretion. Insulin mRNA was reduced in islets from mice fed a HFD but normalized in the IL-1Ra group. Our results show that IL-1Ra improves β-cell survival and function, and support the potential role for IL-1Ra in the treatment of diabetes.

scholarly journals Chronic noise-exposure exacerbates insulin resistance and promotes the manifestations of the type 2 diabetes in a high-fat diet mouse model

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0195411 ◽  
Author(s):  
Lijie Liu ◽  
Yi Huang ◽  
Cong Fang ◽  
Hongyu Zhang ◽  
Jing Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
High Fat Diet ◽  
Noise Exposure ◽  
High Fat

scholarly journals Mitochondrial amidoxime-reducing component 2 (MARC2) has a significant role in N-reductive activity and energy metabolism

2019 ◽  
Vol 294 (46) ◽  
pp. 17593-17602 ◽  
Author(s):  
Sophia Rixen ◽  
Antje Havemeyer ◽  
Anita Tyl-Bielicka ◽  
Kazimiera Pysniak ◽  
Marta Gajewska ◽  
...  
Keyword(s):  
Mouse Model ◽  
Drug Metabolism ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Reductase Activity ◽  
Sequence Similarity ◽  
Significant Activity ◽  
High Fat

The mitochondrial amidoxime-reducing component (MARC) is a mammalian molybdenum-containing enzyme. All annotated mammalian genomes harbor two MARC genes, MARC1 and MARC2, which share a high degree of sequence similarity. Both molybdoenzymes reduce a variety of N-hydroxylated compounds. Besides their role in N-reductive drug metabolism, only little is known about their physiological functions. In this study, we characterized an existing KO mouse model lacking the functional MARC2 gene and fed a high-fat diet and also performed in vivo and in vitro experiments to characterize reductase activity toward known MARC substrates. MARC2 KO significantly decreased reductase activity toward several N-oxygenated substrates, and for typical MARC substrates, only small residual reductive activity was still detectable in MARC2 KO mice. The residual detected reductase activity in MARC2 KO mice could be explained by MARC1 expression that was hardly unaffected by KO, and we found no evidence of significant activity of other reductase enzymes. These results clearly indicate that MARC2 is mainly responsible for N-reductive biotransformation in mice. Striking phenotypical features of MARC2 KO mice were lower body weight, increased body temperature, decreased levels of total cholesterol, and increased glucose levels, supporting previous findings that MARC2 affects energy pathways. Of note, the MARC2 KO mice were resistant to high-fat diet–induced obesity. We propose that the MARC2 KO mouse model could be a powerful tool for predicting MARC-mediated drug metabolism and further investigating MARC's roles in energy homeostasis.

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