Biology subjects

Eriksson, J. W.

Publications and source records attributed to Eriksson, J. W..

3 recordsLinked to original sources

bioRxiv2021

Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues

Defects in pancreatic islets and the progression of multi-tissue insulin resistance in combination with environmental factors are the main causes of type 2 diabetes (T2D). Mass spectrometry-based proteomics of five key-metabolic tissues on a cohort of 42 multi-organ donors provided deep coverage of the proteomes of pancreatic islets, visceral adipose tissue (VAT), liver, skeletal muscle and serum. Enrichment analysis of gene ontology (GO) terms built a tissue-specific map of the chronological order of altered biological processes across healthy controls (CTRL), pre-diabetes (PD) and T2D subjects. This unique dataset allowed us to explore alterations of entire biological pathways and individual proteins in multiple tissues. We confirmed the significant decrease of the citric acid cycle and the respiratory electron transport in VAT and muscle of T2D and we provided a thorough visual representation of the complete set of downregulated proteins. Importantly, we found widespread novel alterations in relevant biological pathways including the increase in hemostasis in pancreatic islets of PD, the increase in the complement cascade in liver and pancreatic islets of PD and the elevation in cholesterol biosynthesis in liver of T2D. Overall, our findings suggest inflammatory, immune and vascular impairments in pancreatic islets as potentially causal factors of insufficient insulin production and increased glucagon levels in the early stages of T2D. In contrast alterations in lipid metabolism and mitochondrial function in the liver and VAT/muscle, respectively, became evident later in manifest T2D. This first multi-tissue proteomic map indicates the temporal order of tissue-specific metabolic dysregulation in T2D development.

cell biology↗

bioRxiv2021

Positional and Compositional Analysis of Saturated, Monounsaturated and Polyunsaturated Fatty acids in Human Adipose Tissue Triglyceride by 13C NMR

Objectives and new findings, ends with short conclusion, no referencesThe synthesis and turnover of triglyceride in adipose tissue involves enzymes with preferences for specific fatty acid classes and/or regioselectivity with regard to the fatty acid position within the glycerol moiety. The focus of the present study was to characterize both the fatty acid composition and their positional distribution in triglycerides of biopsied human subcutaneous adipose tissue using 13C NMR spectroscopy. The triglyceride sn2 position was significantly more enriched with monounsaturated fatty acids compared to the sn1,3 sites, while saturated fatty acids abundance was significantly lower in the sn2 position compared to that of sn1,3. Furthermore, the analysis revealed significant positive correlations between the total fraction of palmitoleic acid with both BMI and HOMA-IR scores. Additionally, we established that 13C NMR chemical shifts for {omega} -3 signals, centered at 31.9 ppm, provided superior resolution of the most abundant FA species, including palmitoleate, compared to the {omega} -2 signals that were used previously. 13C NMR spectroscopy reveals for the first time a highly non-homogenous distribution of FA in the glycerol sites of human adipose tissue triglyceride and that these distributions are correlated with different phenotypes such as BMI and insulin resistance.

biochemistry↗

bioRxiv2018

Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes

Type-2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from a cohort of 43 multi-organ donors. The intra-individual analysis was assessed across five key-metabolic tissues (serum, adipose tissue, liver, pancreatic islets and muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. Carnitines were significantly higher in liver, while lysophosphatidylcholines significantly lower in muscle and serum. An investigation of the progression to overt T2D showed that deoxycholic acid glycine conjugate was significantly higher in liver of pre-diabetes samples while additional increase in T2D was insignificant. A subset of lysophosphatidylcholines were significantly lower in the muscle of pre-diabetes subjects. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

physiology↗