Int J Med Sci 2018; 15(5):417-424. doi:10.7150/ijms.22854

Research Paper

Nutrients restriction upregulates adiponectin in epicardial or subcutaneous adipose tissue: impact in de novo heart failure patients

Rosa M Agra1,2,3, Ángel Fernández-Trasancos2, Esther Díaz-Rodríguez2, Alberto Cordero4, Alfonso Varela-Román1,2,3, Inés Gómez-Otero1,2,3, J Nicolás López- Canoa1, Ángel Luis Fernández3,5, José Manuel Martínez-Cereijo5, José Ramón González-Juanatey1,2,3, Sonia Eiras2,3✉

1. Cardiovascular Area and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Spain
2. Cardiology Group, Health Research Institute of Santiago de Compostela, Spain
3. CIBERCV: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares
4. Cardiology Department, University Hospital of San Juan, Alicante, Spain
5. Heart Surgery, University Clinical Hospital of Santiago de Compostela, Spain

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Agra RM, Fernández-Trasancos Á, Díaz-Rodríguez E, Cordero A, Varela-Román A, Gómez-Otero I, Canoa JNL, Fernández ÁL, Martínez-Cereijo JM, González-Juanatey JR, Eiras S. Nutrients restriction upregulates adiponectin in epicardial or subcutaneous adipose tissue: impact in de novo heart failure patients. Int J Med Sci 2018; 15(5):417-424. doi:10.7150/ijms.22854. Available from

File import instruction


Background: Hyperadiponectinemia is an indicator of worse outcomes in advanced heart failure (HF), its role in de novo HF is less clear.

Objective: Because this protein is a hormone with starvation properties, we wanted to know its association with nutritional state and its regulator factors in de novo HF.

Methods: Adiponectin circulating levels were determined by ELISA at discharge in patients admitted for de novo HF (n=74). Nutritional status was determined by CONUT score. Univariate and multivariate Cox regression analyses were employed to calculate the estimated hazard ratio (HR) with 95% confidence interval (CI) for death or all-cause readmission. Stromal vascular cells (SVC) of EAT and subcutaneous adipose tissue (SAT) from patients (n=5) underwent heart surgery were induced to adipogenesis for 18 days. Then, cells were cultured with complete or starved medium for 8 hours. At the end, adiponectin expression levels were analysed by real time polymerase chain reaction.

Results: Patients were grouped regarding nutritional status. There was a strong association between high adiponectin levels and failing nutritional status. Those patients with worse nutritional state had the highest adiponectin and proBNP levels at discharge (p<0.01). Both proteins were slightly correlated (p<0.05). However, only high adiponectin levels were independently associated with death or all-cause readmission. Nutrients starvation upregulated adiponectin expression levels in adipogenesis-induced SVC from EAT or SAT.

Conclusions: Worse nutritional state in de novo HF patients is associated with higher adiponectin plasma levels. Their levels were upregulated in adipose cells after being nutrients-starved. These results may help us to understand the adiponectin paradox in HF.