Abstract
A growing body of evidence supports a role for tissue-to-diet 15N and 13C discrimination factors (Δ15N and Δ13C), 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 Δ15N and Δ13C 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 Δ15N increases in urine and the protein of the liver and plasma, but Δ15N decreases in the proteins of the heart and the skeletal muscles, alongside Δ13C decreases in all tissue proteins. In Lys, Δ15N 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, Δ13C 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 Δ15N in urine, liver, and plasma proteins reflected an increased AA catabolism occurring at the level of the liver metabolic branch point, while Δ15N 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 Δ15N effects in splanchnic and muscular tissues. In addition, the Δ13C decrease in all tissue proteins, reflects a reduction in carbohydrate (CHO) oxidation and routing towards non-indispensable AA, to achieve fuel economy.
Highlights
IntroductionNatural abundances of the stable carbon and nitrogen heavy isotopes (δ13 C and δ15 N) have been used for decades, in ecological studies, to assess the positions of different organisms in the food chain, and more recently in nutritional epidemiology, as biomarkers of dietary exposure [1,2,3,4,5,6]
Natural abundances of the stable carbon and nitrogen heavy isotopes (δ13 C and δ15 N) have been used for decades, in ecological studies, to assess the positions of different organisms in the food chain, and more recently in nutritional epidemiology, as biomarkers of dietary exposure [1,2,3,4,5,6].Their utilization is based on the observation that the isotopic composition of the body reflects that of the diet, plus a small fractionation factor called the trophic step or discrimination factor, which on average is equal to 1% for 13 C and 3–4% for 15 N [7]
To gain further insight into the underlying mechanisms, we investigated the relationships between δ15 N and protein mass variations in different tissues, and measured the expression of genes coding for the enzymes involved in amino acids (AA) metabolism that might affect their δ15 N
Summary
Natural abundances of the stable carbon and nitrogen heavy isotopes (δ13 C and δ15 N) have been used for decades, in ecological studies, to assess the positions of different organisms in the food chain, and more recently in nutritional epidemiology, as biomarkers of dietary exposure [1,2,3,4,5,6] Their utilization is based on the observation that the isotopic composition of the body reflects that of the diet, plus a small fractionation factor called the trophic step or discrimination factor, which on average is equal to 1% for 13 C and 3–4% for 15 N [7]. These data suggest that δ13 C and δ15 N might represent biomarkers of the catabolic states
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