Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice
Abstract Chronic consumption of Western‐type diet (WD) induces cardiac structural and functional abnormalities. Previously, we have shown that WD consumption in male ATM (ataxia‐telangiectasia mutated kinase) deficient mice associates with accelerated body weight (BW) gain, cardiac systolic dysfunct...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-09-01
|
| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15434 |
| _version_ | 1798001304307499008 |
|---|---|
| author | Mary C. Wingard Suman Dalal Paige L. Shook Paulina Ramirez Muhammad U. Raza Patrick Johnson Barbara A. Connelly Douglas P. Thewke Mahipal Singh Krishna Singh |
| author_facet | Mary C. Wingard Suman Dalal Paige L. Shook Paulina Ramirez Muhammad U. Raza Patrick Johnson Barbara A. Connelly Douglas P. Thewke Mahipal Singh Krishna Singh |
| author_sort | Mary C. Wingard |
| collection | DOAJ |
| description | Abstract Chronic consumption of Western‐type diet (WD) induces cardiac structural and functional abnormalities. Previously, we have shown that WD consumption in male ATM (ataxia‐telangiectasia mutated kinase) deficient mice associates with accelerated body weight (BW) gain, cardiac systolic dysfunction with increased preload, and exacerbation of hypertrophy, apoptosis, and inflammation. This study investigated the role of ATM deficiency in WD‐induced changes in functional and biochemical parameters of the heart in female mice. Six‐week‐old wild‐type (WT) and ATM heterozygous knockout (hKO) female mice were placed on WD or NC (normal chow) for 14 weeks. BW gain, fat accumulation, and cardiac functional and biochemical parameters were measured 14 weeks post‐WD. WD‐induced subcutaneous and total fat contents normalized to body weight were higher in WT‐WD versus hKO‐WD. Heart function measured using echocardiography revealed decreased percent fractional shortening and ejection fraction, and increased LV end systolic diameter and volume in WT‐WD versus WT‐NC. These functional parameters remained unchanged in hKO‐WD versus hKO‐NC. Myocardial fibrosis, myocyte hypertrophy, and apoptosis were higher in WT‐WD versus WT‐NC. However, apoptosis was significantly lower and hypertrophy was significantly higher in hKO‐WD versus WT‐WD. MMP‐9 and Bax expression, and Akt activation were higher in WT‐WD versus WT‐NC. PARP‐1 (full‐length) expression and mTOR activation were lower in WT‐WD versus hKO‐WD. Thus, ATM deficiency in female mice attenuates fat weight gain, preserves heart function, and associates with decreased cardiac cell apoptosis in response to WD. |
| first_indexed | 2024-04-11T11:34:00Z |
| format | Article |
| id | doaj.art-e398068d23c84fd595fc3b5525220b58 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-04-11T11:34:00Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-e398068d23c84fd595fc3b5525220b582022-12-22T04:26:03ZengWileyPhysiological Reports2051-817X2022-09-011018n/an/a10.14814/phy2.15434Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female miceMary C. Wingard0Suman Dalal1Paige L. Shook2Paulina Ramirez3Muhammad U. Raza4Patrick Johnson5Barbara A. Connelly6Douglas P. Thewke7Mahipal Singh8Krishna Singh9Department of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Health Sciences East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USADepartment of Biomedical Sciences James H Quillen College of Medicine, East Tennessee State University Johnson City Tennessee USAAbstract Chronic consumption of Western‐type diet (WD) induces cardiac structural and functional abnormalities. Previously, we have shown that WD consumption in male ATM (ataxia‐telangiectasia mutated kinase) deficient mice associates with accelerated body weight (BW) gain, cardiac systolic dysfunction with increased preload, and exacerbation of hypertrophy, apoptosis, and inflammation. This study investigated the role of ATM deficiency in WD‐induced changes in functional and biochemical parameters of the heart in female mice. Six‐week‐old wild‐type (WT) and ATM heterozygous knockout (hKO) female mice were placed on WD or NC (normal chow) for 14 weeks. BW gain, fat accumulation, and cardiac functional and biochemical parameters were measured 14 weeks post‐WD. WD‐induced subcutaneous and total fat contents normalized to body weight were higher in WT‐WD versus hKO‐WD. Heart function measured using echocardiography revealed decreased percent fractional shortening and ejection fraction, and increased LV end systolic diameter and volume in WT‐WD versus WT‐NC. These functional parameters remained unchanged in hKO‐WD versus hKO‐NC. Myocardial fibrosis, myocyte hypertrophy, and apoptosis were higher in WT‐WD versus WT‐NC. However, apoptosis was significantly lower and hypertrophy was significantly higher in hKO‐WD versus WT‐WD. MMP‐9 and Bax expression, and Akt activation were higher in WT‐WD versus WT‐NC. PARP‐1 (full‐length) expression and mTOR activation were lower in WT‐WD versus hKO‐WD. Thus, ATM deficiency in female mice attenuates fat weight gain, preserves heart function, and associates with decreased cardiac cell apoptosis in response to WD.https://doi.org/10.14814/phy2.15434apoptosisATMfemaleheartWestern‐type diet |
| spellingShingle | Mary C. Wingard Suman Dalal Paige L. Shook Paulina Ramirez Muhammad U. Raza Patrick Johnson Barbara A. Connelly Douglas P. Thewke Mahipal Singh Krishna Singh Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice Physiological Reports apoptosis ATM female heart Western‐type diet |
| title | Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice |
| title_full | Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice |
| title_fullStr | Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice |
| title_full_unstemmed | Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice |
| title_short | Deficiency of ataxia‐telangiectasia mutated kinase attenuates Western‐type diet‐induced cardiac dysfunction in female mice |
| title_sort | deficiency of ataxia telangiectasia mutated kinase attenuates western type diet induced cardiac dysfunction in female mice |
| topic | apoptosis ATM female heart Western‐type diet |
| url | https://doi.org/10.14814/phy2.15434 |
| work_keys_str_mv | AT marycwingard deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT sumandalal deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT paigelshook deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT paulinaramirez deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT muhammaduraza deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT patrickjohnson deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT barbaraaconnelly deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT douglaspthewke deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT mahipalsingh deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice AT krishnasingh deficiencyofataxiatelangiectasiamutatedkinaseattenuateswesterntypedietinducedcardiacdysfunctioninfemalemice |