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Objective: This study investigated remodeling of cellular metabolism and structures during browning of primary human adipocytes derived from both visceral and subcutaneous adipose tissues. Effects of glucocorticoids on the browning were also assessed. Methods: Differentiated omental and subcutaneous human adipocytes were treated with rosiglitazone, with or without dexamethasone, and expression levels of brite adipocyte markers, lipolysis, and lipid droplet and mitochondrial structures were examined. Results: Both omental and subcutaneous adipocytes acquired brite phenotypes upon peroxisome proliferator‐activated receptor‐γ agonist treatment, and dexamethasone tended to enhance the remodeling. Although rosiglitazone increased lipolysis during treatment, brite adipocytes exhibited lower basal lipolytic rates and enhanced responses to β‐adrenergic agonists or atrial natriuretic peptide. Transcriptome analysis identified induction of both breakdown and biosynthesis of lipids in brite adipocytes. After 60+ days in culture, lipid droplet size increased to ~50 microns, becoming almost unilocular in control adipocytes, and after browning, they acquired paucilocular morphology, clusters of small lipid droplets (1–2 micron) surrounded by mitochondria appearing on the periphery of the central large one. Conclusions: Metabolic and structural remodeling during browning of primary human adipocytes is similar to previous findings in human adipocytes in vivo, supporting their uses for mechanical studies investigating browning with translational relevance. [ABSTRACT FROM AUTHOR]

Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here, we describe the functions of linc-ADAIN (adipose anti-inflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and interleukin-8 (IL-8) mRNA stability and translation by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, leads to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo. KD of linc-ADAIN in human adipose stromal cell (ASC) hTERT adipocytes implanted into mice increases adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage. [Display omitted] • linc-ADAIN expression increases during adipocyte differentiation • linc-ADAIN is suppressed in white adipose tissue of obese humans • Knockdown of linc-ADAIN leads to increased inflammation and sustained adipogenesis • linc-ADAIN knockdown increases IL-8 and KLF5 mRNA, important genes for adipogenesis O'Reilly et al. investigate a long non-coding RNA, named linc-adipose anti-inflammatory (linc-ADAIN), and its role in adipose inflammation and maturation of fat cells (adipocytes). They show that linc-ADAIN 's expression is suppressed in adipose tissue of obese humans and that linc-ADAIN regulates inflammation as well as maturation and size of fat cells. [ABSTRACT FROM AUTHOR]