miR-133 links to energy balance through targeting Prdm16.

Adipose (fat) tissues contain white, brown, and beige adipocytes. White adipocytes store extra energy in the form of lipids; ectopic and excessive accumulation of white adipose in the body leads to overweight and obesity, which often causes insulin resistance and Type 2 diabetes. Brown adipocytes, in contrast, contain hundreds of mitochondria per cell, dissipate energy into heat, and are negatively correlated to body weight and insulin resistance (Wu et al., 2013). Under cold temperature or b-adrenergic drug stimulation, a population of 'beige' or 'brite' adipocytes can be formed in the subcutaneous white adipose, containing intermediate levels of mitochondria and consume energy (Wu et al., 2013; Ye et al., 2013). Both brown and beige adipocytes are considered as good fats; and expansion or activation of these types of adipocytes thus represents a novel therapeutic strategy against obesity and diabetes. Among many molecules that affect brown adipocyte biogenesis, Prdm16 is a key tran-scriptional regulator that drives the formation of both brown and beige adipocytes (Seale et al., 2008). Prdm16 also determines the bi-directional fate switch of muscle cells and brown adipocytes. Overexpression of Prdm16 transforms white adipocytes and myoblasts into brown adi-pocytes, while loss of Prdm16 conversely switches brown preadipocytes into muscle cells (Seale et al., 2008). Thus, Prdm16 represents a novel molecular nexus that can be stimulated to expand brown/beige adipocytes and increases energy expenditures. For example, the major Type 2 diabetic drug Rosiglitazone functions by stabilizing Prdm16 protein and promoting brown fat gene program in white adipocytes (Ohno et al., 2012). Mechanistically, Prdm16 functions as a PPARg2 co-activator and defines a specific set of PPARg2 transcriptional targets involved in brown adipogenesis. Given the importance of Prdm16 in brown adipocyte biogenesis, it is critical to understand how Prdm16 is regulated at the tran-scriptional and/or post-transcriptional levels. Recently, three groups have independently reported that miR-133a/b regulates Prdm16 expression and play roles in energy balance Trajkovski et al. (2012) screened adipose microRNAs that respond to cold environment in a mouse model. The mice were maintained at 88C for 24 h, whereas the control mice were housed under room temperature. Both miR-133a and miR-133b were downregulated 5 folds in brown adipose by cold exposure. The data indicated a possible physiological role of miR-133 in brown adipocyte function, especially in maintaining the body temperature. Indeed, with the use of immortalized brown adipocyte cell (PIBA), Trajkovski and colleagues showed that overexpression of miR-133 decreased brown adipogenesis, …