Figure 2. Model of physiological regulation of lipid membrane composition in obesity. Reproduced under the terms of the Creative Commons Attribution Licence from Pietiläinen et al., PLoS Biol. (2011).
A new approach was then introduced to model lipidomics data from membrane lipids by comprehensive molecular dynamics simulations. The computer modelling of lipid membranes indicated that the new lipids observed in the cells of the obese twins balanced each other in such a way that overall membrane fluidity was unaffected. The results therefore suggest that lipidcontent changes in obese individuals might actually be an adaptation that serves to preserve membrane function as the cells expand. Additional analyses suggested that this adaptation can only go so far, and breaks down in the morbidly obese. Membrane lipids a possible marker of diabetes risk Furthermore, elucidation of the adaptive mechanism for maintaining membrane function in growing adipocytes also provides a clue to the potential new targets for preventing or treating obesity-related complications.
In the same twin study, statistical network analysis was applied to attempt to identify the regulatory mechanisms underpinning the adaptive changes. The analysis found that the gene encoding the fatty acid elongase Elovl6 might be involved in fatty acid remodelling in obese people. This finding was further validated in vitro. When Elovl6 was silenced in an adipocyte cell line, the cells could no longer maintain the right level of the adaptive lipids observed in obese twins. In summary, the study described above revealed how lipid membranes of adipocytes remodel to maintain normal membrane function in metabolically compensated individuals, and how this adaptation breaks down in individuals characterised by metabolic complications of obesity. Adipocyte membranes may hold answers to the early pathophysiological processes leading to diabetes. Consequently, measurement of adipose tissue membrane lipids or their Âcorrelates from serum could provide powerful
The adaptation that serves to preserve membrane function can only go so far.
VTT IMPULSE – SCIENCE
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