Differential changes to splanchnic and peripheral protein metabolism during the diet-induced development of metabolic syndrome in rats.

Little is known about the effects of the development of metabolic syndrome (MS) on protein and amino acid (AA) metabolism. During this study, we took advantage of the variability in inter-individual susceptibility to high-fat diet-induced MS to study the relationships between MS, protein synthesis and AA catabolism in multiple tissues in rats. After 4 months of high-fat feeding, an MS score (ZMS) was calculated as the average of the z-scores for individual MS components (weight, adiposities, HOMA-IR, triglycerides). In the small intestine, liver, plasma, kidneys, heart and muscles, tissue protein synthesis was measured by 2H2O labelling, and we evaluated the proportion of tissue AA catabolism (relative to protein synthesis) and nutrient routing to non-indispensable AA in tissue proteins using natural nitrogen and carbon isotopic distances between tissue proteins and nutrients (Δ15N and Δ13C), respectively. In the liver, protein mass and synthesis increased while the proportion of AA catabolism decreased with ZMS. By contrast, in muscles, we found no association between ZMS and protein mass, protein synthesis (except for a weak positive association in the gastrocnemius muscle only), and proportion of AA catabolism. The development of MS was also associated with altered metabolic flexibility and fatty acid oxidation, as shown by less routing of dietary lipids to non-indispensable AA synthesis in liver and muscle. In conclusion, MS development is associated with a greater gain of both fat and protein masses, with higher protein anabolism that mainly occurs in the liver while muscles probably develop anabolic resistance due to insulin resistance.