This investigation integrates the implementation of Proteomic, Metabolomic, and Lipidomic methodologies in several mouse models of obesity and/or hyperglycemia to better comprehend the functional connection between genes, food components, and obese phenotypes. Particularly, the recently incorporated “Western diet”, essentially a High Fat High Sucrose (HFHS) diet enriched in ultra-processed foods, is well-known to trigger a cascade of metabolic disorders leading to obesity, and chronic metabolic alterations such as hepatic steatosis, dyslipidemia, insulin resistance, and type-2 diabetes. However, the molecular mechanisms that control the progression of these diet-induced diseases are mainly unknown, and the discovery of these mechanisms is essential to develop active bioactive compounds with the capacity to prevent obesity and its health side effects. The present study used an HFHS diet to induce obesity and hyperglycemia in mouse models. Then, a SWATH data-independent acquisition (DIA) strategy was used to evaluate changes in the proteome, and several analytical platforms based on mass spectrometry were applied to evaluate changes in a broad spectrum of aqueous metabolites (amino acids, nucleotides, oxoacids…) and lipids (fatty acids, eicosanoids, intact lipids…). Results put into relevance that proteomic, lipidomic, and metabolomic data discriminate animals by diet, but more importantly, clustered animals by disease phenotype. The integration of metabolomic, lipidomic, and proteomic datasets on pathway maps suggests that metabolic differences in the amino acid metabolism, the production of eicosanoids, and the synthesis and accumulation of specific lipid species may contribute to explaining the development of hyperglycemia in obesity. This investigation is proof that the combination of omic methodologies, particularly proteomics, metabolomics, and lipidomics, may provide a comprehensive understanding of the impact of diet components in obesity, but also useful mechanistic information to identify bioactive compounds with the capacity to prevent/revert obesity and related metabolic alterations

3rd Food Chemistry Conference, 10-12 October 2023, Dresden, Germany

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