Endocrine Abstracts

Background: Brown adipose tissue (BAT) thermogenesis offers an appealing prospect to combat obesity. Obesity is characterised by a state of chronic inflammation in adipose tissue mediated by the secretion of a range of inflammatory-cytokines. Our previous work has highlighted that a gut-derived inflammatory agent, lipopolysaccharide (LPS), reduces brown adipocyte activity, insulin sensitivity and mitochondrial-function and is increased with obesity and type 2 diabetes mellitus (T2DM). However, the wide range effects of LPS on brown adipocyte function are unclear. Therefore, the aims of this study were to investigate the spectrum of LPS actions in brown adipocyte and their secretory function, as well as to identify novel factors to explore their therapeutic potential against obesity.

Methods: Murine immortalized brown adipocytes were differentiated with or without LPS (100ng/ml). mRNA and secreted-protein were collected for RNA-sequencing and Proteome Profiler Array analysis.

Results: RNA-Seq analysis revealed that thermogenesis and extracellular matrix (ECM)-receptor interaction were among the top KEGG-pathways significantly (negatively/positively, respectively) enriched in LPS-treated brown adipocytes (P < 0.0001), which also included negatively-enriched mitochondrial respiration and oxidation pathways (P < 0.0001). In accord with RNA-Seq data, LPS-treated brown adipocytes showed not only increased secretion of classical inflammatory factors but also increased levels of novel cytokines, compared to control. Nineteen cytokines were identified as being induced by LPS. Within this group were novel brown adipocyte-secreted cytokines: VCAM-1 (5.5 fold increase, P < 0.01), Endostatin (4.5 fold increase, P < 0.05), Angiopoietin-1 (4.5 fold increase, P < 0.0001).

Conclusions: This study provides evidence that LPS alters the thermogenic components of brown adipocytes at transcriptional and secretion levels. The inflammatory microenvironment results from secretion of cytokines from brown adipocytes themselves upon LPS-treatment, representing an important target to prevent reduced thermogenic potential in brown adipocytes during obesity. Therefore, combatting the effects of inflammation in BAT may help to reduce the impact of obesity and its subsequent consequences.