Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity.

Girolamo Di Maio,Silverio Perrotta,Marcellino Monda,Giovanni Di Bernardo,Ibrahim Halil Demirsoy,Gianfranco Peluso,Nicola Alessio

doi:10.3390/cells10020403

Abstract

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

Highlights

Overweight and obesity are described by the World Health Organization (WHO)as aberrant or superfluous fat accumulation that is dangerous for health due to their association with chronic multifactorial conditions; they cause a great burden in terms of healthcare costs [1,2,3,4].For a long time, adipose tissue was considered as a passive energy storage area; only at the end of the previous century was it identified as the body’s principal “factory”, able to manufacture various hormones and adipokines which play a fundamental action in food intake, energy homoeostasis, insulin sensitivity, angiogenesis, and blood pressure [5]
It is considered an endocrine organ that plays a crucial role in metabolism [6]. Most of these properties can be ascribed to white adipose tissue (WAT), which represents a deposit of energy overbalance as triglycerides in a single lipid droplet that invade the majority of the adipocytes’ volume and a few mitochondria scattered along the nucleus border [7]
We evaluated the effects of several browning agents during white adipocyte differentiation of mesenchymal stromal cells (MSCs), which are able to differentiate both in brown and white adipocytes [20,21]

Summary

Introduction

Overweight and obesity are described by the World Health Organization (WHO)as aberrant or superfluous fat accumulation that is dangerous for health due to their association with chronic multifactorial conditions (e.g., type 2 diabetes, some types of cancers, and cardiovascular diseases); they cause a great burden in terms of healthcare costs [1,2,3,4].For a long time, adipose tissue was considered as a passive energy storage area; only at the end of the previous century was it identified as the body’s principal “factory”, able to manufacture various hormones and adipokines (signaling molecules) which play a fundamental action in food intake, energy homoeostasis, insulin sensitivity, angiogenesis, and blood pressure [5]. It is considered an endocrine organ that plays a crucial role in metabolism [6]. Most of these properties can be ascribed to white adipose tissue (WAT), which represents a deposit of energy overbalance as triglycerides in a single lipid droplet that invade the majority of the adipocytes’ volume and a few mitochondria scattered along the nucleus border [7]. Brown adipocytes present in brown adipose tissue (BAT) are involved in glucose and lipid homeostasis as well as in modulating body temperature, spreading energy by producing heat via UCP1 protein Brown adipocytes contain a high number of mitochondria and multiple lipid droplets [8,9]

Methods

Results

Conclusion