Fat Quality Matters: Distinct Proteomic Signatures Between Lean and Obese Cardiac Visceral Adipose Tissue Underlie its Differential Myocardial Impact

Autores da FMUP

• Diana Margarida Gonçalves Solha Pereira Da Silva

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

• Inês Maria Falcão Sousa Pires Marques

  Autor

Participantes de fora da FMUP

• Concei??o, G
• Matos, J
• Goncalves, N.
• Sousa Mendes, C
• Gon?alves, A
• Ferreira, R
• Vitorino, R.

Unidades de investigação

• Cirurgia e Fisiologia

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

BACKGROUND/AIMS: Heart failure with preserved ejection fraction (HFpEF) is recognised as an important cause of cardiovascular mortality and morbidity, accounting for approximately 50% of heart failure cases. Metabolic-related complications, such as obesity, have been associated with the pathophysiology of this complex syndrome. The anatomic proximity between cardiac visceral adipose tissue (CVAT) and the myocardium has been drawing attention due to its potential pathogenic role in cardiac diseases. Thus, we aimed to characterise the phenotypic and proteomic differences between CVAT from ZSF1 lean (control) and ZSF1 obese (HFpEF) rats as well as to evaluate the myocardial impact of conditioned media derived from CVAT of these 2 groups. METHODS: CVAT of 20-weeks-old lean and obese ZSF1 rats was collected for: 1) 24h DMEM incubation to obtain conditioned media, 2) separation of proteins to mass spectrometry identification, 3) adipokines expression, 4) adipocytes cross-sectional area assessment. Organotypic cultures were prepared from 7 days-old Wistar Han cardiac explants and incubated for 24h with the conditioned media. After incubation, cross-section area of cardiomyocytes and fibrosis were evaluated. Cardiomyocytes were isolated from Wistar Han and incubated with conditioned media for viability studies. RESULTS: CVAT from lean rats presented a higher expression of uncoupling protein-1 (UCP-1) protein, associated with a multilocular appearance and an increased expression of brown adipose tissue markers. Contrarily, CVAT from obese rats revealed a white adipose tissue-like phenotype accompanied by hypertrophy of adipocytes. The analysis of the CVAT proteome reinforced the phenotypic differences between lean and obese CVAT, showing enrichment of proteins involved in triglyceride metabolic processes in obese CVAT. In contrast, mitochondrial proteins were prominent in lean CVAT, further suggesting a brown adipose tissue-like phenotype. The twenty-four hours-long incubation of myocardial organo-cultures with conditioned media obtained from CVAT obese (CM-obese) rats significantly reduced cell viability, induced cardiomyocytes hypertrophy and fibrosis, in stark contrast with the incubation with the conditioned media from lean rats CVAT (CM-lean). Furthermore, the deleterious effect imposed by CM-obese was associated with a pro-inflammatory profile, characterised by an increased expression of several pro-inflammatory adipokines. CONCLUSION: Obesity promotes alterations in CVAT proteome signature, structure, composition and secretome, translating into dramatic myocardial consequences. ? Copyright by the Author(s). Published by Cell Physiol Biochem Press.

© Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Keywords

• Adipocytes; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Cell Survival; Fibrosis; Inflammation; Intra-Abdominal Fat; Mass Spectrometry; Metabolic Syndrome; Mitochondria; Myocardium; Myocytes, Cardiac; Obesity; Organoids; Proteome; Proteomics; Rats; Rats, Wistar; Triglycerides; Uncoupling Protein 1; adipocytokine; mitochondrial protein; uncoupling protein 1; proteome; triacylglycerol; uncoupling protein 1; adipocyte; adult; animal cell; animal experiment; animal model; animal tissue; Article; bioinformatics; cardiac muscle cell; cell isolation; cell viability; controlled study; diastolic dysfunction; heart muscle fibrosis; heart tissue; heart ventricle hypertrophy; intra-abdominal fat; mass spectrometry; metabolic syndrome X; morphometry; newborn; nonhuman; obesity; phenotype; priority journal; protein analysis; protein expression; proteomics; rat; real time polymerase chain reaction; separation technique; Western blotting; Wistar Hannover rat; ZSF1 rat; animal; brown adipose