Role of murine macrophage in temporal regulation of cortisol and serotonin induced adipogenesis in pre-adipocytes when grown together

Sushri Priyadarshini,Palok Aich,Biswaranjan Pradhan

doi:10.1242/bio.034629

Sushri Priyadarshini, Palok Aich + Show 1 more

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https://doi.org/10.1242/bio.034629

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Abstract

ABSTRACTRegulation of adipogenesis, the root cause for obesity, is very poorly understood. However, studies have presented evidence of immuno-metabolic regulation of adipose tissue during periods of chronic psychological stress, leading to adverse conditions related to stress manifestation, including visceral obesity and atherosclerosis. Despite pronounced association of hormonal markers of stress with dys-regulated metabolic states, the contributing signalling events are yet to be established. It is apparent that to understand contributing signalling events we need a model. Although an in vivo model is preferred, it is difficult to establish. The current report, therefore, presents an in vitro model system for the simulation of adipose tissue in a chronic stress micro-environment by growing pre-adipocytes with macrophages in the presence and absence of stress hormones. In this report, effects of cortisol and serotonin on the kinetics of immune and metabolic changes in adipocytes and macrophage (alone and co-cultured) was studied through whole genome transcriptome profiling. A transition from pro- to anti-inflammatory response in the immune profile of pre-adipocytes, with increasing time in co-culture with macrophages, was observed. This transition was reversed by stress hormones cortisol and/or serotonin.

Highlights

IntroductionApart from being the primary energy reserve and an important endocrine organ (Kershaw and Flier, 2004), is a source of fat-derived metabolically active substances (Fain, 2006; Quinkler et al, 2006; Richelsen, 1992; Tang et al, 2015) that are potent pathogenic contributors in modulating systemic inflammatory homeostasis (Fan et al, 2012; Tang et al, 2015)
Unless otherwise mentioned, all comparisons were made for preadipocytes cultured in the presence of macrophages with respect to time matched pre-adipocytes grown in the absence of macrophages
Kinetics of differentially regulated genes in pre-adipocytes grown in the presence and absence of macrophages The transcription kinetics of pre-adipocytes co-cultured with macrophages was compared with pre-adipocytes grown alone at 6 h, 24 h and 48 h to identify the genes responsible for interactive modulation of inflammatory and metabolic adipocyte function, and phenotype in co-culture

Summary

Introduction

Apart from being the primary energy reserve and an important endocrine organ (Kershaw and Flier, 2004), is a source of fat-derived metabolically active substances (Fain, 2006; Quinkler et al, 2006; Richelsen, 1992; Tang et al, 2015) that are potent pathogenic contributors in modulating systemic inflammatory homeostasis (Fan et al, 2012; Tang et al, 2015). Secretion of adipokines leads to systemic low-grade inflammation, as well as altered dynamics of lipid storage to promote secondary diseases. Received 29 March 2018; Accepted 23 July 2018 through ectopic lipid accumulation, which can lead to metabolic syndromes such as obesity, energy disorders and diabetes (Fan et al, 2012; Suganami et al, 2012; Tang et al, 2015) These disorders, marked by inflammation of adipose tissue, are regulated by infiltration of immune-inflammatory cells and cytokines. ATMs have enormous lipid storage capacity in the form of lipid droplets (Aouadi et al, 2014) and can undergo lipolysis, thereby serving as an important source of free fatty acids and glycerol, which are known regulators of adipose tissue metabolism (Michaud et al, 2013; Saraswathi and Hasty, 2006)

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