Does TBC1D4 (AS160) or TBC1D1 Deficiency Affect the Expression of Fatty Acid Handling Proteins in the Adipocytes Differentiated from Human Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Obtained from Subcutaneous and Visceral Fat Depots?

Agnieszka Mikłosz,Piotr Myśliwiec,Elżbieta Supruniuk,Kamil Grubczak,Bartłomiej Łukaszuk,Adrian Chabowski,Marcin Moniuszko,Barbara Choromańska

doi:10.3390/cells10061515

Agnieszka Mikłosz, Piotr Myśliwiec + Show 6 more

Open Access

https://doi.org/10.3390/cells10061515

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Journal: Cells	Publication Date: Jun 16, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: Medical University of Białystok

Abstract

TBC1D4 (AS160) and TBC1D1 are Rab GTPase-activating proteins that play a key role in the regulation of glucose and possibly the transport of long chain fatty acids (LCFAs) into muscle and fat cells. Knockdown (KD) of TBC1D4 increased CD36/SR-B2 and FABPpm protein expressions in L6 myotubes, whereas in murine cardiomyocytes, TBC1D4 deficiency led to a redistribution of CD36/SR-B2 to the sarcolemma. In our study, we investigated the previously unexplored role of both Rab-GAPs in LCFAs uptake in human adipocytes differentiated from the ADMSCs of subcutaneous and visceral adipose tissue origin. To this end we performed a single- and double-knockdown of the proteins (TBC1D1 and TBC1D4). Herein, we provide evidence that AS160 mediates fatty acid entry into the adipocytes derived from ADMSCs. TBC1D4 KD resulted in quite a few alterations to the cellular phenotype, the most obvious of which was the shift of the CD36/SR-B2 transport protein to the plasma membrane. The above translated into an increased uptake of saturated long-chain fatty acid. Interestingly, we observed a tissue-specific pattern, with more pronounced changes present in the adipocytes derived from subADMSCs. Altogether, our data show that in human adipocytes, TBC1D4, but not TBC1D1, deficiency increases LCFAs transport via CD36/SR-B2 translocation.

Highlights

Adipose tissue had long been considered a quiescent fat-storage site; recent research into adipocytes, especially of white adipose tissue (WAT) origin, has altered that perception [1]
We explored the biological role of the two Rab-GTPase activating proteins (RabGAPs) vitally involved in adipocyte substrate utilisation, namely TBC1D1 and/or TBC1D4 [7,8,9]
We evaluated the properties of the Adiposetissue-derived mesenchymal stem cells (ADMSCs) obtained from the subcutaneous and visceral adipose tissue of lean patients

Summary

Introduction

Adipose tissue had long been considered a quiescent fat-storage site; recent research into adipocytes, especially of white adipose tissue (WAT) origin, has altered that perception [1]. WAT may be divided into two major fat depots, i.e., subcutaneous (SAT) and visceral fat (VAT). The quantity of the latter of the two is positively correlated with an increased health burden, while SAT is instead considered an energy storage space and safety buffer against the negative consequences of obesity [3]. Much attention is being paid to ADMSCs, which, in contrast to bone-marrow-derived MSCs (mesenchymal stem cells), are more numerous and are readily accessible using minimally invasive surgical procedures. This makes ADMSCs an important alternative source of stem cells suitable for clinical applications. Recent studies demonstrated ADMSCs’ potential as a treatment for metabolic complications of obesity, i.e., hyperglycemia, hyperinsulinemia, insulin resistance, T2DM, dyslipidemia and cardiovascular complications [4,5,6]

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