NNMT is induced dynamically during beige adipogenesis in adipose tissues depot-specific manner

Nicotinamide N-methyltransferase (NNMT) is a novel regulator, shown recently to regulate adipose tissue energy expenditure partly through changing NAD + content, which is essential for mitochondrial. We determine whether NNMT plays important role in energy metabolism during the beige adipogenesis in vivo and in vitro. Male C57BL/6 mice at 8 weeks old were exposed to 4 ℃ for 1, 2, 3, 4, and 5 days, respectively. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT), and epididymal WAT (eWAT) were harvested for gene and protein expression analysis and the correlation analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without β3-adrenoceptor agonist (CL316, 243) were also harvested for these analyses. A combination of NNMT and its related genetic (Nmnat1, Nampt, Cyp2e1, Nrk1, Cd38) and proteic analyses and also the NAD + levels demonstrated the dynamical and depot-specific remodeling of NAD metabolism in different adipose tissues in response to cold exposure. While upon CL316, 243 treatment, gene expression of Nnmt, Nampt, Cyp2e1, and Nrk1 was all significantly decreased in WA but not in BA. The increased NAD + amount in BA and WA during the beige adipogenesis was observed. Besides, it is demonstrated that the expression of NNMT both in sWAT and WA showed significant negative correlation with browning markers UCP-1 and PGC-1α at protein levels. Above all, NNMT was induced in WAT during the 'cold remodeling' phase and correlated negatively with the process of browning in sWAT and WA, indicating the specific role of NNMT in the regulation of energy homeostasis during the process of beige adipogenesis. (AU)

Human thermogenic adipocytes: a reflection on types of adipocyte, developmental origin, and potential application

Obesity is a leading health problem facing the modern world; however, no effective therapy for this health issue has yet been developed. A promising research direction to identify novel therapies to prevent obesity has emerged from discoveries on development and function of brown/brite adipocytes in mammals. Importantly, there is evidence for the presence and function of active thermogenic brown adipocytes in both infants and adult humans. Several new investigations have shown that thermogenic adipocytes are beneficial to maintain glucose homeostasis, insulin sensitivity, and a healthy body fat content. Such thermogenic adipocytes have been considered as targets to develop a therapy for preventing obesity. This short review seeks to highlight recent findings on the development and function of brown/brite adipocytes in humans and to discuss potential treatments based on these adipocytes to reduce obesity and its related disorders (AU)

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MicroRNAs involved in the browning process of adipocytes

The present review focuses on the role of miRNAs in the control of white adipose tissue browning, a process which describes the recruitment of adipocytes showing features of brown adipocytes in white adipose tissue. MicroRNAs (miRNAs) are a class of short non-coding RNAs (19-22 nucleotides) involved in gene regulation. Although the main effect of miRNAs is the inhibition of the translational machinery, thereby preventing the production of the protein product, the activation of protein translation has also been described in the literature. In addition to modifying translation, miRNAs binding to its target mRNAs also trigger the recruitment and association of mRNA decay factors, leading to mRNA destabilization, degradation, and thus to the decrease in expression levels. Although a great number of miRNAs have been reported to potentially regulate genes that play important roles in the browning process, only a reduced number of studies have demonstrated experimentally an effect on this process associated to changes in miRNA expressions, so far. These studies have shown, by using either primary adipocyte cultures or experimental models of mice (KO mice, mice overexpressing a specific miRNA) that miR-196a, miR-26 and miR-30 are needed for browning process development. By contrast, miR-155, miR-133, miR-27b and miR-34 act as negative regulators of this process. Further studies are needed to fully describe the miRNA network-involved white adipose tissue browning regulation (AU)

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Erratum to: MicroRNAs involved in the browning process of adipocytes

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