The month of August came with a set of newly-published lipidomics publications which made use of Lipotype Shotgun Lipidomics.
Chronic kidney disease
Clinical risk factors explain only a fraction of the variability of eGFR decline in people with type 2 diabetes. However, cross-omics technologies have the potential to identify additional biomarkers for the refinement of prognosis.
Putting together proteomics, metabolomics and lipidomics panel assay measurements and the clinical factor eGFR, the investigation unraveled the predictor biomarker KIM-1.
This is the first publication of the BEAt-DKD consortium which receives funding under IMI of the EU.
Nano-scale lipid organization
The plasma membrane is composed of a complex lipid mixture that forms heterogeneous membrane environments. Physiological events are controlled by small-scale lipid organization.
The investigation unraveled that some proteins are critical for the synthesis of the lipid phosphatidylinositol (4,5)-bisphosphate, a key regulator of dynamic events at the plasma membrane. Ultimately, they control global plasma membrane organization and dynamics.
Lipid droplet size
Lipid droplet breakdown in hepatocytes (liver cells) is mediated by a combination of lipolysis and a selective autophagic mechanism called lipophagy. However, the relationship of these seemingly distinct pathways remained unclear – until now.
This study found that inhibition of lipolysis, lipophagy, or both resulted in similar overall lipid droplet content but dramatic differences in their form. Inhibition of the lipolysis enzyme ATGL resulted in large cytoplasmic lipid droplets, whereas lysosomal inhibition caused the accumulation of numerous small ones within the cytoplasm. The combination of both resulted in large droplets.
Alterations of the liver in diabetes
The liver regulates the availability of insulin to other tissues. It is the first organ physiologically exposed to higher insulin concentrations. The molecular consequences of chronic insulin deficiency for the liver have now been studied systematically.
The analyses revealed increased activities in amino acid metabolism, oxidation of fatty acids, ketogenesis, and gluconeogenesis in the liver samples. The first multi-omics study of a clinically relevant diabetic large animal model revealed molecular signatures and key drivers of functional alterations of the liver in insulin-deficient diabetes.
Resources
1 – Integrative analysis of prognostic biomarkers derived from multiomics panels helps discrimination of chronic kidney disease trajectories in people with type 2 diabetes
2 – Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis
3 – Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes
4 – Multi-omics insights into functional alterations of the liver in insulin-deficient diabetes mellitus
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