Fareeba Sheedfar

Overgewicht, een gezondheidstoestand waarbij de inname van energie groter is dan het verbruik ervan, vormt een wereldwijd probleem in de huidige maatschappij. De toename in overgewicht gaat gepaard met een stijging in overgewicht gerelateerde ziekten, zoals type 2 diabetes (T2D) en niet-alcoholische leververvetting (NAFLD). NAFLD is wereldwijd de grootste veroorzaker van leverziekte. Het begint met vet ophoping in de lever, beter bekend als lever steatose. Deze goedaardige en omkeerbare toestand van NAFLD kan echter uitgroeien tot een leverontsteking ofwel een niet-alcoholische steatohepatitis (NASH), welke vervolgens kan doorgroeien tot fibrose, cirrose en uiteindelijk een hepatocellulair carcinoom (HCC). Toch worden de pathogenese van NAFLD en de mechanismen, die verantwoordelijk zijn voor de progressie van de ziekte, onvoldoende begrepen. Het in dit proefschrift beschreven onderzoek werd uitgevoerd om meer inzicht te krijgen in de etiologie, het verloop van de ziekte en het effec...

Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD), yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL) expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp2...

Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy.AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks ...

Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains speculative. Thus, we aimed to elucidate the sequence of inflammatory events in adipose and hepatic tissues to determine their contribution to the development of metabolic inflammation and insulin resistance (IR) in diet-induced obesity. To confirm our hypothesis that adipose tissue (AT) inflammation is initiated prior to hepatic inflammation, C57BL/6J male mice were fed a low-fat diet (LFD; 10% kcal fat) or high-fat diet (HFD; 45% kcal fat) for either 24, 40 or 52 weeks. Lipid accumulation and inflammation was measured in AT and liver. Glucose tolerance was assessed and plasma levels of glucose, insulin, leptin and adiponectin were measured at variou...

ABSTRACT Obesity and aging are associated with a state of chronic low-grade inflammation, initiated by nutrient overload. Although, fatty acids are inducers of inflammatory signaling in the liver, little is known regarding the mechanisms that link lipid availability at the cell membrane to inflammation.

The academic landscape of the Netherlands has been influenced in recent years by new governmental policies regarding open access and open science, national and European legal guidelines, developments in ICT, and changes in how researchers are assessed. The University of Groningen Library (UB) has seized the opportunity in these developments, providing research support in the domains of registration and archiving of research output, open access publishing, research data management, and research analytics. Increased efficiency in traditional library procedures and the introduction of project-based funding have provided staff capacity for these developments. Full-service customization, to meet the needs of researchers and alleviate their time and work pressure, lies at the heart of the UB's research support.

Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n = 52) received a control low-fat diet (LFD; 10 kcal% fat) for 6 weeks followed by 24 weeks of either LFD (n = 13) or high-fat diet (HFD; 45 kcal% fat; n = 13) or HFD supplemented with 0.1% w/w of the flavanol compound epicatechin (HFD+E; n = 13) or an anthocyanin-rich bilberry extract (HFD+B; n = 13). Energy substrate utilization was determined by indirect calorimetry in a subset of mice following the dietary switch and at the end of the experiment. Blood samples were collected at baseline and at 3 days and 4, 12, and 20 weeks after dietary switch and analyzed for systemic lipids and proinflammatory cytokines. Adipo...