Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes

Abstract

BackgroundNorepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level.ResultsWe used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses.ConclusionsAltogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5173-0) contains supplementary material, which is available to authorized users.

Chronic cAMP activation induces adipocyte browning through discordant biphasic remodeling of transcriptome and chromatin accessibility

“…This started increasing instantly after cAMP activation and stayed relatively high during the entire adipocyte browning for 3 days. These results are in line with a previous report of NFIL3 as a candidate transcriptional regulator of short-term norepinephrine stimulation in adipocytes [ 78 ]. Interestingly, Nfil3 knockdown by shNfil3 led to reduced thermogenic gene expression, as well as cellular respiration only during chronic, but not acute, cAMP activation.…”

Adipocytes and macrophages secretomes coregulate catecholamine-synthesizing enzymes

“…We may speculate that CA synthesis and downstream cellular fat regulation is more determinant in early stages of adipogenic differentiation due to the impact that inflammation might have on CA synthesis and their role in adipogenesis. For instance, NA stimulation of adipocytes induces downregulation of PPARγ among other white adipocytes marker genes 22 . The expression of PPARγ in preadipocytes was diminished after both cytokines and LPS treatments, but was unaffected in mature adipocytes.…”

Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats

“…In normal conditions, leptin suppresses insulin secretion through central actions and through direct effects on pancreatic beta cells resulting in the reduction of insulin levels. However, in obesity, this signaling is altered causing LR which promotes obesity, hyperinsulinemia, and IR [38]. Circulating levels of leptin are proportional to the amount of body fat, and therefore, there is hyperphagia despite there being leptin excess, leading to LR [39].…”