Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD, n = 15) and AGE-enriched diet (AGE-D, n = 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased Nε-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements.

Pathological alterations in cell functions are frequently accompanied by metabolic reprogramming including modifications in amino acid metabolism. Amino acid detection is thus integral to the diagnosis of many hereditary metabolic diseases. The development of malignant diseases as metabolic disorders comes along with a complex dysregulation of genetic and epigenetic factors affecting metabolic enzymes. Cancer cells might transiently or permanently become auxotrophic for non-essential or semi-essential amino acids such as asparagine or arginine. Also, transformed cells are often more susceptible to local shortage of essential amino acids such as methionine than normal tissues. This offers new points of attacking unique metabolic features in cancer cells. To better understand these processes, highly sensitive methods for amino acid detection and quantification are required. Our review summarizes the main methodologies for amino acid detection with a particular focus on applications in biomedicine and cancer, provides a historical overview of the methodological pre-requisites in amino acid analytics. We compare classical and modern approaches such as the combination of gas chromatography and liquid chromatography with mass spectrometry (GC-MS/LC-MS). The latter is increasingly applied in clinical routine. We therefore illustrate an LC-MS workflow for analyzing arginine and methionine as well as their precursors and analogs in biological material. Pitfalls during protocol development are discussed, but LC-MS emerges as a reliable and sensitive tool for the detection of amino acids in biological matrices. Quantification is challenging, but of particular interest in cancer research as targeting arginine and methionine turnover in cancer cells represent novel treatment strategies.