SGBS cells as a model of human adipocyte browning: A comprehensive comparative study with primary human white subcutaneous adipocytes

Chia Rou Yeo,E Shyong Tai,Madhur Agrawal,Shawn Hoon,Sue-Anne Toh,M Shabeer Yassin,Manu Kunaal Shrivastava,Shiqi Huang,Antonio Vidal-Puig,Vanna Chhay,Asim Shabbir,Chin Meng Khoo

doi:10.1038/s41598-017-04369-2

Abstract

The Simpson Golabi Behmel Syndrome (SGBS) pre-adipocyte cell strain is widely considered to be a representative in vitro model of human white pre-adipocytes. A recent study suggested that SGBS adipocytes exhibit an unexpected transient brown phenotype. Here, we comprehensively examined key differences between SGBS adipocytes and primary human white subcutaneous (PHWSC) adipocytes. RNA-Seq analysis revealed that extracellular matrix (ECM)-receptor interaction and metabolic pathways were the top two KEGG pathways significantly enriched in SGBS adipocytes, which included positively enriched mitochondrial respiration and oxidation pathways. Compared to PHWSC adipocytes, SGBS adipocytes showed not only greater induction of adipogenic gene expression during differentiation but also increased levels of UCP1 mRNA and protein expression. Functionally, SGBS adipocytes displayed higher ISO-induced basal leak respiration and overall oxygen consumption rate, along with increased triglyceride accumulation and insulin-stimulated glucose uptake. In conclusion, we confirmed that SGBS adipocytes, which are considered of white adipose tissue origin can shift towards a brown/beige adipocyte phenotype. These differences indicate SGBS cells may help to identify mechanisms leading to browning, and inform our understanding for the use of SGBS vis-à-vis primary human subcutaneous adipocytes as a human white adipocyte model, guiding the selection of appropriate cell models in future metabolic research.

Highlights

The Simpson Golabi Behmel Syndrome (SGBS) pre-adipocyte cell strain is widely considered to be a representative in vitro model of human white pre-adipocytes
20 KEGG pathways were enriched in SGBS when compared to primary human white subcutaneous (PHWSC) adipocytes and the top 2 significantly enhanced pathways were extracellular matrix (ECM)-receptor interaction (FDR = 3.18E-06) and metabolic pathways (FDR = 3.07E-05) (Table 1)
The interaction map highlighted significant positive enrichment in oxidative phosphorylation, TCA cycle, fatty acid elongation, butanoate metabolism and steroid biosynthesis pathways in SGBS adipocytes when compared to PHWSC adipocytes (Supplementary Fig. S2 and Supplementary Table S4)

Summary

Introduction

The Simpson Golabi Behmel Syndrome (SGBS) pre-adipocyte cell strain is widely considered to be a representative in vitro model of human white pre-adipocytes. Another study characterizing SGBS adipocytes and primary human omental adipocytes derived from obese and non-obese individuals concurred that the cell lines are similar in terms of the morphology, induction of adipocyte-specific gene expression and GPDH activity[13]. We conducted a comparative study and found that while both these cell types have overlapping similarities, they exhibit distinct metabolic signatures that may explain differences in their capacities for adipocyte differentiation and maturation, lipid metabolism and thermogenic activity Understanding these differences could open opportunities to understand the browning of adipose tissue and further our knowledge of the strength and limitations of each cell line and provide guidance on the choice of cellular models in future research on human fat cell development and metabolism

Methods

Results

Conclusion