Effect of lipopolysaccharides on adipogenic potential and premature senescence of adipocyte progenitors

Abstract

Zhao M, Chen X. Effect of lipopolysaccharides on adipogenic potential and premature senescence of adipocyte progenitors. Am J Physiol Endocrinol Metab 309: E334 -E344, 2015. First published June 23, 2015; doi:10.1152/ajpendo.00601.2014.-The elevation of circulating LPS has been associated with obesity and aging. However, whether and how LPS contributes to adipose tissue dysfunction is unclear. In this study, we investigated the effect of LPS on the adipogenic capacity and cellular senescence of adipocyte progenitors. Stromal-vascular cells were isolated from inguinal adipose tissue of C57BL/6 mice and treated with LPS during the different time periods of adipocyte differentiation. We found that LPS treatment for 24 h prior to the induction of differentiation led to the most profound effect on the inhibition of adipogenesis, as evidenced by the morphological changes and the decreased mRNA expression of adipocyte marker genes. In addition, LPS induced features of premature senescence of SV cells, including the activation of p53, the elevation of SA-␤-gal activity, and increased hydrogen peroxide production, but not telomere length. Upon LPS treatment, SV cells also developed senescence-associated secretory phenotype (SASP), as demonstrated by the increased expression of TNF␣, IL-1␤, IL-6, MCP-1, and VEGF␣. Blocking LPS-induced NF-B activation and cytokine production by Bay 11-7082 failed to rescue the impaired adipogenesis and the reduction in PPAR␥ and Zfp423 expression. On the contrary, rosiglitazone had little effect on cytokine production but corrected the defective adipogenic potential. In conclusion, we demonstrate that LPS inhibits adipogenesis by disrupting the differentiation of adipocyte progenitors in a NF-B-independent manner; LPS also induces premature senescence of adipocyte progenitors. Our data suggest that LPS could be a potential contributor to the defective adipogenesis and the development of cellular senescence in adipose tissue during obesity and aging.lipopolysaccharides; adipocyte progenitors; adipogenesis; cellular senescence THE MAIN FUNCTIONS OF WHITE ADIPOSE TISSUE (WAT) are to store lipids and secrete metabolic regulators of adipokines and cytokines. Dysfunctional adipose tissue, characterized by reduced adipogenesis and increased cellular senescence and inflammation, commonly associates with obesity and aging (52). Adipose tissue dysfunction impairs lipid storage and dysregulates production of adipokines and cytokines, leading to metabolic derangement, adipose tissue inflammation,insulin resistance, and type 2 diabetes (3,12,15,26).Adipogenesis relies on the formation of new adipocytes from adipocyte progenitor cells. Adequate adipogenesis capacity is essential to sequester lipids in adipose tissue, which protects against the ectopic fat deposition and the development of insulin resistance (37,38,46). Adipocyte hyperplasia has been considered as a protective mechanism when compared with adipocyte hypertrophy in terms of the metabolic consequences of adipose tissue expansion (47). In di...

Role of TLR4 in the induction of inflammatory changes in adipocytes and macrophages

“…LPS is an endotoxin, that may not necessarily increase lipid content in adipocytes but serves as a ligand for TLR4 induced inflammatory pathways [32] that may eventually inhibit adipocyte differentiation. It could be speculated that only adipocyte differentiation was affected directly by TLR4 activation or through lipid metabolism which may be in contrast to some other studies due to differences in LPS treatment periods [60]. However, the lack of cell count after the differentiation process might be a limitation in our study.…”

Fat depot-specific differences of macrophage infiltration and cellular senescence in obese bovine adipose tissues

“…“Replicative senescence” is associated with the cellular aging process affected by telomere shortening [ 35 , 41 ]. In contrast, “premature senescence” is induced by stressors such as oxidative stress and ROS without telomere-independent mechanisms [ 51 , 57 ]. Our previous study indicated that telomere length was not associated with adipocyte hypertrophy from three anatomical sites (subcutaneous, visceral and intramuscular) in obese cattle [ 56 ].…”

Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing

“…It has been demonstrated that senescent adipose-derived stromal/progenitor cells in response to an adipogenic hormone cocktail show reduced expression of key adipogenic regulators and impaired expression of adipogenic differentiation genes, including adiponectin (Mitterberger et al 2014 ). In another study, Zhao and Chen investigated whether elevated lipopolysaccharides (LPS) which has been associated with obesity, contribute to induction of cellular senescence and impaired adipogenic capacity (Zhao and Chen 2015 ). Stromal-vascular cells isolated from adipose tissue of mice subjected to LPS underwent induction of cellular senescence and a decrease in expression of adipocyte marker genes.…”