Insulin-like growth factor-1 short-period therapy improves cardiomyopathy stimulating cardiac progenitor cells survival in obese mice

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2020-01, Vol.30 (1), p.151-161
• Main Authors: Andrade, Daniela, Oliveira, Genilza, Menezes, Luciana, Nascimento, Ana Lúcia, Carvalho, Simone, Stumbo, Ana Carolina, Thole, Alessandra, Garcia-Souza, Érica, Moura, Anibal, Carvalho, Laís, Cortez, Erika
• Format: Article
• Language: English
• Subjects: Cardiac progenitor cells; Cardiovascular disease; IGF-1; Obesity
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2019.09.001

Cardiovascular diseases are the main cause of mortality in obesity. Despite advanced understanding, the mechanisms that regulate cardiac progenitor cells (CPC) survival in pathological conditions are not clear. Low IGF-1 plasma levels are correlated to obesity, cardiomyopathy and CPC death, so this work aimed to investigate IGF-1 therapeutic potential on cardiomyopathy and its relationship with the survival, proliferation and differentiation of CPC in Western diet-induced obesity. Male Swiss mice were divided into control group (CG, n = 8), fed with standard diet; and obese group (OG, n = 16), fed with Western diet, for 12 weeks. At 11th week, OG was subdivided to receive a daily subcutaneous injection of human recombinant IGF-1 (100 μg.Kg−1) for seven consecutive days (OG + IGF1, n = 8). Results showed that IGF-1 therapy improved the metabolic parameters negatively impacted by western diet in OG, reaching levels similar to CG. OG + IGF-1 also demonstrated restored heart energetic metabolism, fibrosis resolution, decreased apoptosis level, restored cardiac gap junctions and intracellular calcium balance. Cardiomyopathy improvement was accompanied by increased CPC survival, proliferation and newly cardiomyocytes formation related to increased pAkt/Akt ratio. These results suggest that only one week of IGF-1 therapy has cardioprotective effects through Akt pathway upregulation, ensuring CPC survival and differentiation, contributing to heart failure rescue. •One week of IGF-1 therapy improves metabolic and biometric profile of obese mice.•One week of IGF-1 therapy reverses cardiomyopathy process in obese mice.•IGF-1 therapy improves CPC survival via Akt signaling pathway upregulation.•IGF-1 therapy stimulates new cardiomyocytes formation in obese mice.