PMID- 31100870 OWN - NLM STAT- MEDLINE DCOM- 20200106 LR - 20200225 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 11 IP - 5 DP - 2019 May 16 TI - Natural Isotope Abundances of Carbon and Nitrogen in Tissue Proteins and Amino Acids as Biomarkers of the Decreased Carbohydrate Oxidation and Increased Amino Acid Oxidation Induced by Caloric Restriction under a Maintained Protein Intake in Obese Rats. LID - 10.3390/nu11051087 [doi] LID - 1087 AB - A growing body of evidence supports a role for tissue-to-diet (15)N and (13)C discrimination factors (Delta(15)N and Delta(13)C), as biomarkers of metabolic adaptations to nutritional stress, but the underlying mechanisms remain poorly understood. In obese rats fed ad libitum or subjected to gradual caloric restriction (CR), under a maintained protein intake, we measured Delta(15)N and Delta(13)C levels in tissue proteins and their constitutive amino acids (AA) and the expression of enzymes involved in the AA metabolism. CR was found to lower protein mass in the intestine, liver, heart and, to a lesser extent, some skeletal muscles. This was accompanied by Delta(15)N increases in urine and the protein of the liver and plasma, but Delta(15)N decreases in the proteins of the heart and the skeletal muscles, alongside Delta(13)C decreases in all tissue proteins. In Lys, Delta(15)N levels rose in the plasma, intestine, and some muscles, but fell in the heart, while in Ala, and to a lesser extent Glx and Asx, Delta(13)C levels fell in all these tissues. In the liver, CR was associated with an increase in the expression of genes involved in AA oxidation. During CR, the parallel rises of Delta(15)N in urine, liver, and plasma proteins reflected an increased AA catabolism occurring at the level of the liver metabolic branch point, while Delta(15)N decreases in cardiac and skeletal muscle proteins indicated increased protein and AA catabolism in these tissues. Thus, an increased protein and AA catabolism results in opposite Delta(15)N effects in splanchnic and muscular tissues. In addition, the Delta(13)C decrease in all tissue proteins, reflects a reduction in carbohydrate (CHO) oxidation and routing towards non-indispensable AA, to achieve fuel economy. FAU - Huneau, Jean-Francois AU - Huneau JF AUID- ORCID: 0000-0001-7336-2617 AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. jean-francois.huneau@agroparistech.fr. FAU - Mantha, Olivier L AU - Mantha OL AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. olmantha@gmail.com. FAU - Hermier, Dominique AU - Hermier D AUID- ORCID: 0000-0001-8676-6960 AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. dominique.hermier@agroparistech.fr. FAU - Mathe, Veronique AU - Mathe V AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. veronique.mathe@agroparistech.fr. FAU - Galmiche, Guillaume AU - Galmiche G AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. ggalmiche@gmail.com. FAU - Mariotti, Francois AU - Mariotti F AUID- ORCID: 0000-0002-4516-3853 AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. francois.mariotti@agroparistech.fr. FAU - Fouillet, Helene AU - Fouillet H AUID- ORCID: 0000-0003-3932-251X AD - UMR PNCA, AgroParisTech, INRA, Universite Paris-Saclay, 75005 Paris, France. helene.fouillet@agroparistech.fr. LA - eng GR - 910P1A/Terres Univia/ GR - 3-14-02/Groupe Lipides Nutrition/ PT - Journal Article DEP - 20190516 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Amino Acids) RN - 0 (Biomarkers) RN - 0 (Carbon Isotopes) RN - 0 (Dietary Proteins) RN - 0 (Nitrogen Isotopes) RN - 0 (Proteins) SB - IM MH - Amino Acids/*chemistry/metabolism MH - Animal Feed MH - Animals MH - Biomarkers MH - *Caloric Restriction MH - Carbohydrate Metabolism MH - *Carbon Isotopes MH - Diet/veterinary MH - Dietary Proteins/*administration & dosage MH - Humans MH - Male MH - *Nitrogen Isotopes MH - Oxidation-Reduction MH - Proteins/*chemistry/metabolism MH - Random Allocation MH - Rats MH - Rats, Wistar PMC - PMC6567081 OTO - NOTNLM OT - 13C and 15N natural isotope abundance OT - amino acid oxidation OT - caloric restriction OT - dietary nutrient routing OT - obesity COIS- The authors declare no conflict of interest. EDAT- 2019/05/19 06:00 MHDA- 2020/01/07 06:00 PMCR- 2019/05/01 CRDT- 2019/05/19 06:00 PHST- 2019/03/25 00:00 [received] PHST- 2019/05/10 00:00 [revised] PHST- 2019/05/14 00:00 [accepted] PHST- 2019/05/19 06:00 [entrez] PHST- 2019/05/19 06:00 [pubmed] PHST- 2020/01/07 06:00 [medline] PHST- 2019/05/01 00:00 [pmc-release] AID - nu11051087 [pii] AID - nutrients-11-01087 [pii] AID - 10.3390/nu11051087 [doi] PST - epublish SO - Nutrients. 2019 May 16;11(5):1087. doi: 10.3390/nu11051087.