RESUMO
Compounds derived from plants have been widely studied in the context of metabolic diseases and associated clinical conditions. In this regard, although the effects of Camellia sinensis plant, from which various types of teas, such as green tea, originate, have been vastly reported in the literature, the mechanisms underlying these effects remain elusive. A deep search of the literature showed that green tea's action in different cells, tissues, and diseases is an open field in the research of microRNAs (miRNAs). miRNAs are important communicator molecules between cells in different tissues implicated in diverse cellular pathways. They have emerged as an important linkage between physiology and pathophysiology, raising the issue of polyphenols can act also by changing miRNA expression. miRNAs are short, non-coding endogenous RNA, which silence the gene functions by targeting messenger RNA (mRNA) through degradation or translation repression. Therefore, the aim of this review is to present the studies that show the main compounds of green tea modulating the expression of miRNAs in inflammation, adipose tissue, skeletal muscle, and liver. We provide an overview of a few studies that have tried to demonstrate the role of miRNAs associated with the beneficial effects of compounds from green tea. We have emphasized that there is still a considerable gap in the literature investigating the role and likely involvement of miRNAs in the extensive beneficial health effects of green tea compounds already described, indicating miRNAs as potential polyphenols' mediators with a promising field to be investigated.
Assuntos
Camellia sinensis , MicroRNAs , Chá , MicroRNAs/genética , MicroRNAs/metabolismo , Polifenóis/farmacologia , Polifenóis/metabolismo , Camellia sinensis/genética , Camellia sinensis/metabolismo , RNA Mensageiro/metabolismoRESUMO
Adipocytes exhibit different morphological and functional characteristics, depending on their anatomical location, developmental origin, and stimulus. While white adipocytes tend to accumulate energy as triglycerides, brown and beige adipocytes tend to direct carbon sources to fuel thermogenesis. White and beige adipocytes originate from common progenitor cells, which are distinct from brown adipocyte precursors. Having a method to study white vs. beige vs. brown adipocyte differentiation may help to unveil the mechanisms driving distinct adipogenic programs. Preadipocytes can be cultured and differentiated in vitro using a combination of compounds to stimulate adipogenesis. Here, we describe and compare protocols designed to stimulate adipocyte differentiation and induce brown/beige-like or white-like characteristics in differentiating adipocytes. The protocols consist in exposing murine preadipocytes to pharmacological stimuli aimed at triggering adipogenesis and inducing (or not) a thermogenic gene expression program. After 8 days of differentiation with a pro-browning cocktail, immortalized preadipocytes isolated from interscapular brown fat (9B cells) or inguinal white fat (9W cells) from the same mouse expressed higher levels of brown/beige adipocyte markers (e.g., Ucp1) and pan-adipocyte differentiation markers (e.g., Pparg, Cebpa and aP2) when compared to the same cells differentiated with a cocktail that lacked brown/beige adipogenic inducers (i.e., rosiglitazone, T3, and indomethacin). Consistent with a higher thermogenic potential of brown vs. beige adipocytes, differentiated 9B cells expressed higher Ucp1 levels than differentiated 9W cells. This simple protocol may help researchers to understand mechanisms of adipogenesis and how adipocytes become thermogenic.
RESUMO
MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. Enoxacin mitigated diet-induced obesity in mice, and this was associated with increased energy expenditure. Consistently, subcutaneous white and brown adipose tissues and skeletal muscle of enoxacin-treated mice had higher levels of markers associated with thermogenesis and oxidative metabolism. These effects were cell autonomous since they were recapitulated in vitro in murine and human cell models. In preadipocytes, enoxacin led to a reduction of miR-34a-5p expression and up-regulation of its target genes (e.g., Fgfr1, Klb, and Sirt1), thus increasing FGF21 signaling and promoting beige adipogenesis. Our data demonstrate that enoxacin counteracts obesity by promoting thermogenic signaling and inducing oxidative metabolism in adipose tissue and skeletal muscle in a mechanism that involves, at least in part, miRNA-mediated regulation.