MicroRNA-34a and Impaired FGF19/21 Signaling in Obesity.

The obesity epidemic and the urgent need for effective and safe drugs to treat obesity-related diseases have greatly increased research interest in the metabolic hormones, fibroblast growth factor-19 (FGF19, FGF15 in mice), and FGF21. FGF19 and FGF21 function as endocrine hormones that play key roles in energy metabolism and counteract obesity. Importantly, in obese humans and lab animals, circulating FGF19 and FGF21 levels are elevated, and metabolic actions of these hormones are impaired but the underlying mechanisms remained unknown. Recent microRNA (miR) studies have revealed that aberrantly elevated miR-34a in obesity directly targets β-Klotho, the obligate coreceptor for both FGF19 and FGF21, and attenuates metabolic signaling of these hormones. In this review, we will discuss recent findings in the miR and FGF19/21 fields, emphasizing the novel function of obesity-associated miR-34a in attenuation of FGF19/21 metabolic actions, and further discuss miRs, including miR-34a, as potential drug targets for obesity-related diseases.