Liu, LingbinYi, JiaqingRay, W. KeithVu, Lucas T.Helm, Richard F.Siegel, Paul B.Cline, Mark A.Gilbert, Elizabeth R.2019-07-242019-07-242019Liu et al. Nutrition and Diabetes (2019) 9:13 https://doi.org/10.1038/s41387-019-0081-1http://hdl.handle.net/10919/91964Background: The hypothalamus is the ultimate modulator of appetite and energy balance and therefore sensitive to changes in nutritional state. Chicks from lines selected for low (LWS) and high (HWS) body weight are hypophagic and compulsive eaters, respectively, and differ in their propensity to become obese and in their hypothalamic mRNA response to fasting. Methods: As fasting-induced changes in hypothalamic proteins are unknown, we investigated the hypothalamic proteomes of 5-day old LWS and HWS chicks in the fed and fasted states using a label-free liquid chromatographytandem mass spectrometry (LC-MS/MS) approach. Results: A total of 744 proteins were identified in the chicken hypothalamus, and 268 differentially abundant proteins were identified among four pairwise comparisons. Ninety-five proteins were associated with the response to fasting in HWS chicks, and 23 proteins were associated with the response to fasting in LWS chicks. Fasting-responsive proteins in HWS chicks were significantly enriched in ATP metabolic processes, glyoxylate/dicarboxylate metabolism, and ribosome function. There was no enrichment for any pathways in LWS chicks in response to fasting. In the fasted and fed states, 159 and 119 proteins differed between HWS and LWS, respectively. Oxidative phosphorylation, citric acid cycle, and carbon metabolism were the main pathways associated with differences between the two lines of chicks. Enzymes associated with metabolic pathways differed between HWS and LWS in both nutritional states, including fumarase, aspartate aminotransferase, mitochondrial GOT2, 3-hydroxyisobutyrate dehydrogenase, chondrogenesis associated lipocalin, sialic acid synthase, arylamine N-acetyltransferase, pineal gland isozyme NAT-3, and succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial. Conclusions: These results provide insights into the hypothalamic metabolic pathways that are affected by nutritional status and the regulation of appetite and eating behavior.13 pagesapplication/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereedhttps://doi.org/10.1038/s41387-019-0081-19