Heterozygous caveolin-3 mice show increased susceptibility to palmitate-induced insulin resistance

Talukder, Milton; Preda, Marilena; Ryzhova, Larisa; Prudovsky, Igor; Pinz, Ilka

doi:10.14814/phy2.12736

Cited by 22 publications

(22 citation statements)

References 42 publications

(62 reference statements)

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“…It can induce IR in liver cells, skeletal muscles and cardiomyocytes, and plays an important role in the formation of diseases such as atherosclerosis and diabetes. [25][26][27] In this study, PA levels in GDM and PE patients showed an upward trend, and GDM were more prominent than PE patients. PA inhibits insulin-stimulated cellular glucose transport and increases blood glucose levels by attenuating tyrosine phosphorylation of the insulin receptor substrate and inhibiting the activation of phosphoinositide 3-kinase, which blocks insulin signaling.…”

Section: Fatty Acidssupporting

confidence: 48%

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Teng

Zhang

et al. 2020

J of Obstet and Gynaecol

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Aim The aim of the study was to investigate the difference of the serum metabolic profile between gestational diabetes mellitus (GDM) patients and preeclampsia (PE) patients, to establish the disease differentiation model and to find characteristic metabolites, in order to provide a new idea for the occurrence, development and treatment of the disease. Methods Twenty‐nine patients with GDM group and 29 PE group who were examined in Tianjin No. 3 Central Hospital from March 2018 to August 2018 were enrolled as case group, and 29 normal pregnant women were selected as control group. All the serum samples were analyzed by using the ultra‐performance liquid chromatography and mass spectrometry. Based on the multivariate statistical analysis method of pattern recognition, we screened out and identified the differential characteristic metabolites. Results The serum metabolic profile model of GDM group and PE group was successfully constructed. A total of nine characteristic metabolites were screened and identified in this study, including LPC 18:0, LPC 22:6, LPC 16:0, (S)‐14‐methylhexadecanoic acid, behenic acid, palmitic acid, sphingosine, phytosphingosine and 1,25‐dihydroxyvitamin D3‐26,23‐lactone. Among them, six characteristic metabolites which were LPC 18:0, LPC 22:6, behenic acid, palmitic acid, sphingosine and 1,25‐dihydroxyvitamin D3‐26,23‐lactone all had a significant statistical difference among GDM, PE and normal pregnancy groups (P < 0.05). Conclusion The construction of metabolic profile discriminant model has a strong ability to differentiate GDM patients from PE pregnant women. The screened characteristic metabolites can early reflect the disorder of lipid, calcium and phosphorus metabolism of patients, and provide reference and help for the discussion of the occurrence, development and treatment of diseases.

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Section: Fatty Acidssupporting

confidence: 48%

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Teng

Zhang

et al. 2020

J of Obstet and Gynaecol

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“…In humans, partial gene deficiencies in multiple loci, rather than complete loss of function of a given gene, underlie complex diseases such as obesity and Type 2 diabetes (22). Other studies examining the effects of heterozygosity on glucose and lipid metabolism have underscored the additional insights gained from mouse models of partial gene deficiency that are relevant to human disease variants (1,17,42). Therefore, our results highlight the value of examining the consequences of partial gene deficiency in preclinical animal models of complex diseases, as these data will provide a basis to help interpret and evaluate functional consequences of reduced gene expression due to polymorphisms or epigenetic changes in the gene regulatory regions uncovered by large-scale genome-wide studies in humans.…”

Section: Discussionmentioning

confidence: 99%

Partial deficiency of CTRP12 alters hepatic lipid metabolism

Tan

Little

Lei

et al. 2016

Physiological Genomics

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Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/-) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/-) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/-) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/-) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/-) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes.

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“…Echocardiography was performed with a Vevo2100 (VisualSonics), 40 MHz solid-state transducer, and the papillary muscle was used as orientation for the acquisition of short-axis M-mode images. Data were analyzed by the heart function package provided by VisualSonics Systems [10]. Diastolic and systolic LV internal dimensions were measured to evaluate LV structural changes.…”

Section: Cardiac Ultrasoundmentioning

confidence: 99%

Systemic and cardiac susceptibility of immune compromised mice to doxorubicin

Favreau-Lessard¹,

Blaszyk²,

Jones³

et al. 2019

Cardio-Oncology

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Background: Anthracycline chemotherapy is an effective and widely used treatment for solid tumors and hematological malignancies regardless of its known cardiotoxicity. The mechanisms of the cardiotoxicity are not fully understood and methods to protect the heart during or following anthracycline chemotherapy are currently unclear. In order to examine the efficacy of human cell based therapy in anthracycline-induced injury, we characterized a mouse model using an immune compromised strain of mice capable of accepting human cells.Methods: Immune compromised mice (NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ) were repeatedly exposed to pharmaceutical grade doxorubicin (0.5 mg/kg -4 mg/kg). Cardiotoxicity was assessed by echocardiography and μCT imaging of the coronary vascular bed as well as by flow cytometry and by histological assessments of anthracycline-induced cardiac tissue damage. Results: The immune compromised mice were highly susceptible to doxorubicin treatment. Doxorubicin induced both systemic and cardiac toxicities. Gastrointestinal and hepatic injury occurred at 4 mg/kg and 1.5 mg/kg dosing while mice receiving 0.5 mg/kg weekly only displayed hepatic damage. Repeated exposure to 0.5 mg/kg anthracyclines resulted in cardiac toxicity. Flow cytometric analysis of hearts indicated a loss in endothelial and cardiac progenitor cells after doxorubicin treatment. This endothelial loss is corroborated by the lack of small vessels detected by μCT in the hearts of mice exposed to doxorubicin. Histological assessment shows no overt cardiomyocyte injury but livers from mice treated with doxorubicin show marked hepatic plate atrophy with intracytoplasmic and canalicular cholestasis, rare pericentral hepatocellular necrosis and significant zone 3 iron accumulation, likely an indication of metabolic injury due to doxorubicin toxicity. Conclusions: Immune compromised mice are sensitive to doxorubicin therapy resulting in systemic complications in addition to cardiovascular toxicity. Anthracycline-induced cardiotoxicity is observed at very low doses in NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice.

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Heterozygous caveolin-3 mice show increased susceptibility to palmitate-induced insulin resistance

Cited by 22 publications

References 42 publications

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Partial deficiency of CTRP12 alters hepatic lipid metabolism

Systemic and cardiac susceptibility of immune compromised mice to doxorubicin

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