Post-transcriptional regulation of energy usage: glucose and lipid metabolism

National Institute On Aging

Investigators

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Abstract

The studies in this Project focus on understanding the RBPs and ncRNAs that influence energy metabolism, since the processes that generate energy become impaired with aging. In particular, we have studied the regulation of insulin production, adipogenesis, and autophagy by RBPs and ncRNAs. Glucose homeostasis. With rising appreciation that glucose metabolism is extensively regulated at the post-transcriptional level, we recently identified the HuD as an RBP that associated with the 5UTR of the mRNA encoding insulin and repressed insulin translation (Lee et al., Mol Cell 2012). Accordingly, HuD-null mice had higher levels of insulin, while HuD-overexpressing mice showed lower circulating insulin and displayed a reduced ability to uptake glucose in tissues (Lee et al., Mol Cell 2012). More recently, in collaboration with the Fernndez-Hernando laboratory (New York University), we reported that miR-33 is another key player in glucose homeostasis (Ramirez et al., Mol Cell Biol 2013). On the topic of adipogenesis, we are pursuing further analysis of two microRNAs differentially expressed during adipose tissue differentiation: miR-130a and miR-130b (Lee et al., 2011). Other energy metabolism. During this review period, we also discovered that miR-519, a microRNA that shows increased levels with senescence and targets the HuR mRNA, was a potent trigger of autophagy and a growth repressor (Abdelmohsen et al., Mol Cell Biol 2012). As part of another long-standing initiative to understand the influence of sirtuins on senescence and aging, we collaborated with the de Cabo laboratory (TGB, NIA) in reporting that the sirtuin activator SRT1720 affected mitochondrial respiration and improved the survival and healthspan of obese mice (Minor et al., Sci Reports 2012).