Abstract
Ageing is the most important risk factor for development of metabolic diseases such as obesity and type-2 diabetes. It is emerging that age-related alterations in the biology of the adipose tissue underlie development of metabolic pathologies.
Dietary saturated fatty acids (SAFs) as well as bacterial endotoxins (LPS) have been implicated in the development of insulin resistance. However, there is a controversy as to whether in vivo such effects are mediated by SAFs or LPS as high fat feeding is thought to enhance the permeability of the gut to bacterial endotoxins. SAFs and LPS activate innate immunity signalling pathways, such as Toll-like receptor (TLR) and Tumour Necrosis Factor-a (TNF-a) pathways not only in immune cells, but also in metabolic cells, including adipocytes. However, comprehensive analysis of cell signalling pathway activation by metabolic stressors using high-throughput methods, such as mass spectrometry-based phosphoproteomics, have not been applied readily in the study of stress signalling in metabolic tissues, in the way these have been applied in the context of cancer cell signalling.
Dietary nutrients and microbial components are known to affect metabolic health over the life course. Saturated fatty acids and bacterial endotoxins affect the cells of the immune system and metabolic tissues alike. These molecules are known to cause adverse metabolic effects through activation of inflammatory pathways. Developments in mass spectrometry-based proteomics provide a so far unexploited opportunity to identify signalling pathways activated by metabolic stressors. These pathways can potentially be targeted pharmacologically in the prevention or therapy of age-related metabolic diseases.
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