The RNA-binding protein HuR is a negative regulator in adipogenesis.

Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively. Fat-specific knockout of HuR significantly enhances adipogenic gene program in adipose tissues, accompanied by a systemic glucose intolerance and insulin resistance. HuR knockout also results in depot-specific phenotypes: it can repress myogenesis program in brown fat, enhance inflammation program in epidydimal white fat and induce browning program in inguinal white fat. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts including Insig1, a negative regulator during adipogenesis. Taken together, our work establishes HuR as an important posttranscriptional regulator of adipogenesis and provides insights into how RNA processing contributes to adipocyte development.

RNA Binding Protein Ybx2 Regulates RNA Stability During Cold-Induced Brown Fat Activation.

Recent years have seen an upsurge of interest in brown adipose tissue (BAT) to combat the epidemic of obesity and diabetes. How its development and activation are regulated at the posttranscriptional level, however, has yet to be fully understood. RNA binding proteins (RBPs) lie in the center of posttranscriptional regulation. To systemically study the role of RBPs in BAT, we profiled >400 RBPs in different adipose depots and identified Y-box binding protein 2 (Ybx2) as a novel regulator in BAT activation. Knockdown of Ybx2 blocks brown adipogenesis, whereas its overexpression promotes BAT marker expression in brown and white adipocytes. Ybx2-knockout mice could form BAT but failed to express a full thermogenic program. Integrative analysis of RNA sequencing and RNA-immunoprecipitation study revealed a set of Ybx2's mRNA targets, including Pgc1α, that were destabilized by Ybx2 depletion during cold-induced activation. Thus, Ybx2 is a novel regulator that controls BAT activation by regulating mRNA stability.

Assessment of Preference for Hormonal Treatment-Related Health States among Patients with Breast Cancer.

OBJECTIVES: 1) To obtain preference scores from patients with breast cancer in Singapore for different stages of breast cancer and hormonal therapy-related adverse effects, and 2) to determine the association of patients' demographic and clinical characteristics with those preference scores. METHODS: A total of 22 health states were used to elicit preference values from 64 patients with breast cancer. At each interview, 14 health states were randomly selected and rated by the patient using the visual analogue scale and standard gamble methods to derive health state preference scores, which were recalibrated to the scale of 0 (death) and 1 (perfect health). RESULTS: Mean adjusted visual analogue scale scores ranged from 0.25 (no recurrence with ischemic cerebrovascular events) to 0.82 (no recurrence with no adverse effects). Mean adjusted standard gamble scores ranged from 0.31 (distant recurrence with chemotherapy-related adverse effects) to 0.80 (no recurrence with no adverse effects). Adverse effects ischemic cerebrovascular events and spine fracture resulted in the greatest decline in health state preference scores. Age, ethnicity, education level, and prior chemotherapy were associated with preference scores. Having children was not found to be associated with the preference scores. CONCLUSIONS: Taking into account disease progression and hormonal therapy-related adverse effects as well as their impact on health-related quality of life, this study quantifies patients' preference for various breast cancer-related health states. The findings offer valuable information for future cost-utility analysis of breast cancer treatments.