Beiging Modulates Inflammatory Adipogenesis in Salt-Treated and MEK6-Transfected Adipocytes.

Songjoo Kang,Myoungsook Lee

doi:10.3390/cells10051106

Abstract

To investigate whether the beiging process changes the interactive effects of salt and MEK6 gene on inflammatory adipogenesis, the salt treatment (NaCl 50 mM) and MEK6 transfection of Tg(+/+) cells were performed with white adipocytes (WAT) and beige-like-adipocytes (BLA). BLA induced by T3 were confirmed by UCP-1 expression and the MEK6 protein was 3.5 times higher in MEK6 transfected WAT than the control. The adipogenic genes, PPAR-γ and C/EBP-α, were 1.5 times more highly expressed in the salt-treated groups than the non-salt-treated groups, and adipogenesis was greatly increased in Tg(+/+) WAT compared to non-transfected Tg(−/−). The adipogenesis induced by salt treatment and MEK6 transfection was significantly reduced in BLA. The inflammatory adipocytokines, TNF-α, IL-1β, and IL-6, were increased in the salt-treated Tg(+/+) WAT, but an anti-inflammation biomarker, the adiponectin/leptin ratio, was reduced in Tg(+/+), to tenth of that in Tg(−/−). However, the production of adipocytokines in WAT was strongly weakened in BLA, although a combination of salt and MEK6 transfection had the most significant effects on inflammation in both WAT and BLA. Oxygen consumption in mitochondria was maximized in salt-treated and MEK6 transfected WAT, but it was decreased by 50% in BLA. In conclusion, beiging controls the synergistic effects of salt and MEK6 on adipogenesis, inflammation, and energy expenditure.

Highlights

Various obesogenic factors, such as hormone disorder, energy-dense diets, low physical activity, and oxidative stress, may induce body fat accumulation [1,2,3]
The expression of beiging biomarker, uncoupling protein-1 (UCP-1), in BLA was a double that in white adipocytes (WAT), and we found that MAPK/ERK kinase 6 (MEK6) expression in BLA was
50% lower than WAT. (Figure 1D) We confirmed that MEK6 transfection induced the adipogenic factors, PPAR-γ, C/EBP-α, and aP2 proteins by 4-fold, 3-fold, and 1.5-fold, respectively, compared to Tg(−/−) WAT. (Figure 1C,E) Since the adiponectin/leptin ratio was significantly decreased in MEK6-overexpressed WAT, MEK6 transfection may show the same pattern, with the high production of the inflammatory cytokine, leptin or the low production of the anti-inflammatory cytokine, adiponectin

Summary

Introduction

Various obesogenic factors, such as hormone disorder, energy-dense diets, low physical activity, and oxidative stress, may induce body fat accumulation [1,2,3]. We previously found that salt (NaCl) treatment dose-dependently increased the expression of adipogenic/lipogenic genes and the production of pro-inflammatory adipocytokines in WAT [4]. Salt-loading diets (>15 g NaCl/day for seven days) induced hypoxia in human visceral adipose tissues, which is associated with changes in circulating monocyte subsets (CD14++, CD16+) related to inflammation [5]. The major function of brown adipose tissue in newborns and hibernating mammals is to produce heat through thermogenin, uncoupling protein-1 (UCP-1), by non- shivering thermogenesis instead of through ATP production in the mitochondria of WAT [7]. Mitogen-activated protein kinase kinase 6 (MAP2K6, MKK6) or MAPK/ERK kinase 6 (MEK6) gene was screened through

Methods

Results

Conclusion