SRC-3/AIB-1 may Enhance Hepatic NFATC1 Transcription and Mediate Inflammation in a Tissue-Specific Manner in Morbid Obesity

Athina Chasapi; Konstantinos Balampanis; Anna Tanoglidi; Eleni Kourea; George I Lambrou; Vaia Lambadiari; Fotios Kalfarentzos; Erifili Hatziagelaki; Maria Melachrinou; Georgia Sotiropoulou-Bonikou

doi:10.2174/1871530319666190715160630

SRC-3/AIB-1 may Enhance Hepatic NFATC1 Transcription and Mediate Inflammation in a Tissue-Specific Manner in Morbid Obesity

Endocr Metab Immune Disord Drug Targets. 2020;20(2):242-255. doi: 10.2174/1871530319666190715160630.

Affiliations

¹ Department of Pathology, Medical School, University of Patras, 26500 Patras, Greece.
² Second Department of Internal Medicine, Research Unit and Diabetes Center, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Rimini 1, Haidari, 12462 Athens, Greece.
³ Department of Anatomy and Histology-Embryology, Medical School, University of Patras, 26500 Patras, Greece.
⁴ Department of Clinical Pathology, Akademiska University, Uppsala, Sweden.
⁵ First Department of Pediatrics, Choremeio Research Laboratory, National and Kapodistrian University of Athens, Medical School, Thivon & Levadeias 8, 11527, Goudi, Athens, Greece.
⁶ First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 17, Ag. Thoma St, 11527 Athens, Greece.

PMID: 31322077
DOI: 10.2174/1871530319666190715160630

Abstract

Background: Obesity is a global epidemic which is associated with several cardiometabolic comorbidities and is characterized by chronic, low grade systemic inflammation. Numerous biomarkers have been implicated in the pathophysiology of the disease, including transcription factors and coregulators. Steroid Receptor Coactivator (SRC)-family represent the master regulators of metabolic pathways and their dysregulation is strongly associated with numerous metabolic disorders.

Methods: 50 morbidly obese patients participated in the present study. Biopsies were collected from visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, extra-myocellular adipose tissue and liver. We evaluated the differential protein expression of NFATc1, SRC-2/TIF-2, SRC-3/AIB-1 and inflammatory biomarkers CD68 and CD3 by immunohistochemistry. The current study was designed to determine any correlations between the transcription factor NFATc1 and the SRC coregulators, as well as any associations with the inflammatory biomarkers.

Results: We identified SRC-3 as a hepatic NFATc1 coactivator and we demonstrated its possible role in energy homeostasis and lipid metabolism. Moreover, we revealed a complex and extensive intraand inter-tissue network among the three main investigated proteins and the inflammatory biomarkers, suggesting their potential participation in the obesity-induced inflammatory cascade.

Conclusion: Steroid receptor coactivators are critical regulators of human metabolism with pleiotropic and tissue-specific actions. We believe that our study will contribute to the better understanding of the complex multi-tissue interactions that are disrupted in obesity and can therefore lead to numerous cardiometabolic diseases. Further on, our present findings suggest that SRC-3/AIB-1 could constitute possible future drug targets.

Keywords: Inflammation; Liver (Hepar); NFATc1; Obesity; SRC-3/AIB-1; diabetes; metabolic syndrome..

MeSH terms

Adipose Tissue / metabolism
Adult
Female
Humans
Inflammation Mediators / metabolism*
Liver / metabolism*
Male
Middle Aged
Muscle, Skeletal / metabolism
NFATC Transcription Factors / metabolism*
Nuclear Receptor Coactivator 3 / metabolism*
Obesity, Morbid / diagnosis
Obesity, Morbid / metabolism*

Substances

Inflammation Mediators
NFATC Transcription Factors
NFATC1 protein, human
NCOA3 protein, human
Nuclear Receptor Coactivator 3