Nutritional value of cooked offal derived from free-range rams reared in South Africa

Nutritional value of Dorper (n=10) and Merino (n=10) by-products were evaluated. Proximate composition differed between organs and breeds with Merino heart (68.9 g/100 g), spleen (77.2 g/100 g) and testicles (83.7 g/100 g) having higher moisture contents than their Dorper counterparts. Dorper brain (10.1 g/100 g), heart (15.2 g/100 g), spleen (20.4 g/100 g) and testicles (12.9 g/100 g) had higher protein contents than Merino. Dorper organs also tended to have a lower fat content. Amino acid and fatty acid profiles differed between organs and breeds. Few differences were noted in total SFA and MUFA. Dorper heart (1.8%) had significantly lower total PUFA than Merino heart (7.3%). All the organs showed favourable P:S ratios, with the exception of the tongue, heart and stomach. Dorper and Merino brain, lungs and testicles had favourable n−6/n−3 ratios. Cholesterol content differed between both organs and breeds. The value of offal as food is discussed further.Web of Scienc

Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia

The cellular receptor Notch1 is a central regulator of T-cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T-cell acute lymphoblastic leukemia (T-ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T-ALL. Previously, glutaminolysis inhibition has been proposed to synergize with anti-Notch therapies in T-ALL models. In this work, we report that Notch1 upregulation in T-ALL induced a change in the metabolism of the important amino acid glutamine, preventing glutamine synthesis through the downregulation of glutamine synthetase (GS). Downregulation of GS was responsible for glutamine addiction in Notch1-driven T-ALL both in vitro and in vivo. Our results also confirmed an increase in glutaminolysis mediated by Notch1. Increased glutaminolysis resulted in the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway, a central controller of cell growth. However, glutaminolysis did not play any role in Notch1-induced glutamine addiction. Finally, the combined treatment targeting mTORC1 and limiting glutamine availability had a synergistic effect to induce apoptosis and to prevent Notch1-driven leukemia progression. Our results placed glutamine limitation and mTORC1 inhibition as a potential therapy against Notch1-driven leukemia.This work was supported by funds from the followinginstitutions: Agencia Estatal de Investigacion/Euro-pean Regional Development Fund, European Union(PGC2018-096244-B-I00, SAF2016-75442-R), Ministryof Science, Innovation and Universities of Spain,Spanish National Research Council—CSIC, InstitutNational de la Sante et de la Recherche Medicale—INSERM, Ligue Contre le Cancer—Gironde, Univer-site de Bordeaux, Fondation pour la Recherche Medi-cale, the Conseil Regional d’Aquitaine, SIRIC-BRIO,Fondation ARC and Institut Europeen de Chimie etBiologie. MJN was supported by a bourse d’excellencede la Federation Wallonie-Bruxelles (WBI) and a post-doctoral fellowship from Fondation ARC. We thankVincent Pitard (Flow Cytometry Platform, Universitede Bordeaux, France) for technical assistance in flowcytometry experiments. We thank Diana Cabrera(Metabolomics Platform, CIC bioGUNE, Spain) fortechnical assistance in metabolomics analysi