Human ARRB1 peptide

The objective of this study was to evaluate the effect of high or low energy intake on carcass composition and expression of hypothalamic genes related to the onset of puberty. Twenty-four prepubertal Nellore heifers, 18-20-months-old, with 275.3 +/- 18.0 kg body weight (BW), and 4.9 +/- 0.2 (1-9 scale) body condition score (BCS) were randomly assigned to two treatments: high-energy diet (HE) and low-energy diet (LE). Heifers were housed in two collective pens and fed diets formulated to promote average daily gain of 0.4 (LE) or 1.2 kg (HE) BW/day. Eight heifers from each treatment were slaughtered after the first corpus luteum detection - considered as age of puberty. The 9-10-11th rib section was taken and prepared for carcass composition analyses. Samples from hypothalamus were collected, frozen in liquid nitrogen, and stored at -80 degrees C. Specific primers for targets (NPY, NPY1R, NPY4R, SOCS3, OXT, ARRB1, and IGFPB2) and control (RPL19 and RN18S1) genes were designed for real-time PCR and then the relative quantification of target gene expression was performed. High-energy diets increased body condition score, cold carcass weight, and Longissimus lumborum muscle area and decreased age at slaughter. High-energy diets decreased the expression of NPY1R and ARRB1 at 4.4-fold and 1.5-fold, respectively. In conclusion, the hastening of puberty with high energy intake is related with greater body fatness and lesser hypothalamic expression of NPY1 receptor and of beta-arrestin1, suggesting a less sensitive hypothalamus to the negative effects of NPY signaling.

beta-Arrestins are multifunctional proteins originally identified as negative adaptors of G protein-coupled receptors (GPCRs). Emerging evidence has also indicated that beta-arrestins can activate signaling pathways independent of GPCR activation. This study was to elucidate the role of beta-arrestins in diabetic nephropathy (DN) and hypothesized that beta-arrestins contribute to diabetic renal injury by mediating podocyte autophagic process. We first found that both beta-arrestin-1 and beta-arrestin-2 were upregulated in the kidney from streptozotocin-induced diabetic mice, diabetic db/db mice and kidney biopsies from diabetic patients. We further revealed that either beta-arrestin-1 or beta-arrestin-2 deficiency (Arrb1(-/-) or Arrb2(-/-)) ameliorated renal injury in diabetic mice. In vitro, we observed that podocytes increased both beta-arrestin-1 and beta-arrestin-2 expression levels under hyperglycemia condition and further demonstrated that beta-arrestin-1 and beta-arrestin-2 shared common mechanisms to suppress podocyte autophagy by negative regulation of ATG12-ATG5 conjugation. Collectively, this study for the first time demonstrates that beta-arrestin-1 and beta-arrestin-2 mediate podocyte autophagic activity, indicating that beta-arrestins are critical components of signal transduction pathways that link renal injury to reduce autophagy in DN. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with DN.