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Insulin-like growth factor 1 alleviates high-fat diet-induced myocardial contractile dysfunction: role of insulin signaling and mitochondrial function.
Hypertension. 2012 Mar; 59(3):680-93.H

Abstract

Obesity is often associated with reduced plasma insulin-like growth factor 1 (IGF-1) levels, oxidative stress, mitochondrial damage, and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high-fat diet-induced oxidative, myocardial, geometric, and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low- (10%) or high-fat (45%) diet to induce obesity. High-fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin 6, insulin, and triglyceride, as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end-systolic and end-diastolic diameter, increased wall thickness, and cardiac hypertrophy in high-fat-fed FVB mice. High-fat diet promoted reactive oxygen species generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca(2+) dysregulation (including depressed peak shortening and maximal velocity of shortening/relengthening), prolonged duration of relengthening, and dampened intracellular Ca(2+) rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor and postreceptor signaling molecules insulin receptor substrate 1 (tyrosine/serine phosphorylation), Akt, glycogen synthase kinase 3β, forkhead transcriptional factors, and mammalian target of rapamycin, as well as downregulated expression of mitochondrial proteins peroxisome proliferator-activated receptor-γ coactivator 1α and uncoupling protein 2. Intriguingly, IGF-1 mitigated high-fat-diet feeding-induced alterations in reactive oxygen species, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca(2+) handling, and insulin signaling but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high-fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high-fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly because of preserved cell survival, mitochondrial function, and insulin signaling.

Authors+Show Affiliations

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22275536

Citation

Zhang, Yingmei, et al. "Insulin-like Growth Factor 1 Alleviates High-fat Diet-induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function." Hypertension (Dallas, Tex. : 1979), vol. 59, no. 3, 2012, pp. 680-93.
Zhang Y, Yuan M, Bradley KM, et al. Insulin-like growth factor 1 alleviates high-fat diet-induced myocardial contractile dysfunction: role of insulin signaling and mitochondrial function. Hypertension. 2012;59(3):680-93.
Zhang, Y., Yuan, M., Bradley, K. M., Dong, F., Anversa, P., & Ren, J. (2012). Insulin-like growth factor 1 alleviates high-fat diet-induced myocardial contractile dysfunction: role of insulin signaling and mitochondrial function. Hypertension (Dallas, Tex. : 1979), 59(3), 680-93. https://doi.org/10.1161/HYPERTENSIONAHA.111.181867
Zhang Y, et al. Insulin-like Growth Factor 1 Alleviates High-fat Diet-induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function. Hypertension. 2012;59(3):680-93. PubMed PMID: 22275536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor 1 alleviates high-fat diet-induced myocardial contractile dysfunction: role of insulin signaling and mitochondrial function. AU - Zhang,Yingmei, AU - Yuan,Ming, AU - Bradley,Katherine M, AU - Dong,Feng, AU - Anversa,Piero, AU - Ren,Jun, Y1 - 2012/01/23/ PY - 2012/1/26/entrez PY - 2012/1/26/pubmed PY - 2012/4/18/medline SP - 680 EP - 93 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 59 IS - 3 N2 - Obesity is often associated with reduced plasma insulin-like growth factor 1 (IGF-1) levels, oxidative stress, mitochondrial damage, and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high-fat diet-induced oxidative, myocardial, geometric, and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low- (10%) or high-fat (45%) diet to induce obesity. High-fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin 6, insulin, and triglyceride, as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end-systolic and end-diastolic diameter, increased wall thickness, and cardiac hypertrophy in high-fat-fed FVB mice. High-fat diet promoted reactive oxygen species generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca(2+) dysregulation (including depressed peak shortening and maximal velocity of shortening/relengthening), prolonged duration of relengthening, and dampened intracellular Ca(2+) rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor and postreceptor signaling molecules insulin receptor substrate 1 (tyrosine/serine phosphorylation), Akt, glycogen synthase kinase 3β, forkhead transcriptional factors, and mammalian target of rapamycin, as well as downregulated expression of mitochondrial proteins peroxisome proliferator-activated receptor-γ coactivator 1α and uncoupling protein 2. Intriguingly, IGF-1 mitigated high-fat-diet feeding-induced alterations in reactive oxygen species, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca(2+) handling, and insulin signaling but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high-fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high-fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly because of preserved cell survival, mitochondrial function, and insulin signaling. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/22275536/Insulin_like_growth_factor_1_alleviates_high_fat_diet_induced_myocardial_contractile_dysfunction:_role_of_insulin_signaling_and_mitochondrial_function_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.111.181867?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -