Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus

Type 2 diabetes is associated with excessive food intake and a sedentary lifestyle. Local inflammation of white adipose tissue induces cytokine-mediated insulin resistance of adipocytes. This results in enhanced lipolysis within these cells. The fatty acids that are released into the cytosol can be removed by mitochondrial β-oxidation. The flux through this pathway is normally limited by the rate of ADP supply, which in turn is determined by the metabolic activity of the adipocyte. It is expected that the latter does not adapt to an increased rate of lipolysis. We propose that elevated fatty acid concentrations in the cytosol of adipocytes induce mitochondrial uncoupling and thereby allow mitochondria to remove much larger amounts of fatty acids. By this, release of fatty acids out of adipocytes into the circulation is prevented. When the rate of fatty acid release into the cytosol exceeds the β-oxidation capacity, cytosolic fatty acid concentrations increase and induce mitochondrial toxicity. This results in a decrease in β-oxidation capacity and the entry of fatty acids into the circulation. Unless these released fatty acids are removed by mitochondrial oxidation in active muscles, these fatty acids result in ectopic triacylglycerol deposits, induction of insulin resistance, beta cell damage and diabetes. Thiazolidinediones improve mitochondrial function within adipocytes and may in this way alleviate the burden imposed by the excessive fat accumulation associated with the metabolic syndrome. Thus, the number and activity of mitochondria within adipocytes contribute to the threshold at which fatty acids are released into the circulation, leading to insulin resistance and type 2 diabetes

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients

Designing marine reserves to reflect local socioeconomic conditions: lessons from long-enduring customary management systems

Coral reef conservation strategies such as marine protected areas have met limited success in many developing countries. Some researchers attribute part of these shortcomings to inadequate attention to the social context of conserving marine resources. To gain insights into applying Western conservation theory more successfully in the socioeconomic context of developing countries, this study examines how long-enduring, customary reef closures appear to reflect local socioeconomic conditions in two Papua New Guinean communities. Attributes of the customary management (including size, shape, permanence, and gear restrictions) are examined in relation to prevailing socioeconomic conditions (including resource users’ ability to switch gears, fishing grounds, and occupations). Customary closures in the two communities appear to reflect local socioeconomic circumstances in three ways. First, in situations where people can readily switch between occupations, full closures are acceptable with periodic harvests to benefit from the closure. In comparison, communities with high dependence on the marine resources are more conducive to employing strategies that restrict certain gear types while still allowing others. Second, where there is multiple clan and family spatial ownership of resources, the communities have one closure per clan/family; one large no-take area would have disproportionate affect on those compared to the rest of the community. In contrast, communities that have joint ownership can establish one large closure as long as there are other areas available to harvest. Third, historical and trade relationships with neighboring communities can influence regulations by creating the need for occasional harvests to provide fish for feasts. This study further demonstrates the importance of understanding the socioeconomic context of factors such as community governance and levels of dependence for the conservation of marine resources