Carbohydrate binding modules: diversity of domain architecture in amylases and cellulases from filamentous microorganisms

Microbial Biotechnolog

Angptl4 Upregulates Cholesterol Synthesis in Liver via Inhibition of LPL- and HL- Dependent Hepatic Cholesterol Uptake

Background¿ Dysregulation of plasma lipoprotein levels may increase the risk for atherosclerosis. Recently, angiopoietin-like protein 4, also known as fasting-induced adipose factor Fiaf, was uncovered as a novel modulator of plasma lipoprotein metabolism. Here we take advantage of the fasting-dependent phenotype of Angptl4-transgenic (Angptl4-Tg) mice to better characterize the metabolic function of Angptl4. Methods and Results¿ In 24-hour fasted mice, Angptl4 overexpression increased plasma triglycerides (TG) by 24-fold, which was attributable to elevated VLDL-, IDL/LDL- and HDL-TG content. Angptl4 overexpression decreased post-heparin LPL activity by stimulating conversion of endothelial-bound LPL dimers to circulating LPL monomers. In fasted but not fed state, Angptl4 overexpression severely impaired LPL-dependent plasma TG and cholesteryl ester clearance and subsequent uptake of fatty acids and cholesterol into tissues. Consequently, hepatic cholesterol content was significantly decreased, leading to universal upregulation of cholesterol and fatty acid synthesis pathways and increased rate of cholesterol synthesis. Conclusions¿ The hypertriglyceridemic effect of Angptl4 is attributable to inhibition of LPL-dependent VLDL lipolysis by converting LPL dimers to monomers, and Angptl4 upregulates cholesterol synthesis in liver secondary to inhibition of LPL- and HL-dependent hepatic cholesterol uptake. The present study exploits the fasting-dependent phenotype of Angptl4-transgenic mice to characterize the function of Angptl4. We conclude that: (1) Angptl4 causes hypertriglyceridemia by inhibiting LPL-dependent VLDL lipolysis by converting LPL dimers to monomers, and (2) Angptl4 upregulates hepatic cholesterol synthesis secondary to inhibition of LPL- and HL-dependent hepatic cholesterol uptake

СумДУ на сторінках преси : поточний інформаційний список, липень-серпень 2018 р.

Поточний інформаційний список містить перелік статей про Сумський державний університет з періодичних видань, які надійшли до бібліотеки за липень-серпень

Profile Comparer Extended: phylogeny of lytic polysaccharide monooxygenase families using profile hidden Markov model alignments

Insight into the inter- and intra-family relationship of protein families is important, since it can aid understanding of substrate specificity evolution and assign putative functions to proteins with unknown function. To study both these inter- and intra-family relationships, the ability to build phylogenetic trees using the most sensitive sequence similarity search methods (e.g. profile hidden Markov model (pHMM)–pHMM alignments) is required. However, existing solutions require a very long calculation time to obtain the phylogenetic tree. Therefore, a faster protocol is required to make this approach efficient for research. To contribute to this goal, we extended the original Profile Comparer program (PRC) for the construction of large pHMM phylogenetic trees at speeds several orders of magnitude faster compared to pHMM-tree. As an example, PRC Extended (PRCx) was used to study the phylogeny of over 10,000 sequences of lytic polysaccharide monooxygenase (LPMO) from over seven families. Using the newly developed program we were able to reveal previously unknown homologs of LPMOs, namely the PFAM Egh16-like family. Moreover, we show that the substrate specificities have evolved independently several times within the LPMO superfamily. Furthermore, the LPMO phylogenetic tree, does not seem to follow taxonomy-based classification.Microbial Biotechnolog

LXR beta deficient mice have reduced hepatic insulin clearance during hyperinsulinemic euglucemic clamp

The present study addresses the insulin sensitivity in mice deficient in LXR beta (LXR beta(-/-)) as well as in wild type (wt) mice assessed by hyperinsulinemic euglycemic clamp Wt and LXR beta(-/-) mice were fed either a normal chow diet or a high fat and high cholesterol diet (HFCD), and Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamps We show that LXR beta(-/-) mice have reduced insulin clearance during hyperinsulinemic clamps upon feeding both HFCD and a regular chow diet Moreover we also observed reduced hepatic inflammation in LXR beta(-/-) mice compared to wt mice upon feeding an HFCD, despite equal levels of hepatic steatosis. In summary, our results indicate that LXR beta(-/-) mice have reduced insulin clearance during hyperinsulinemic euglycemic clamps and also reduced hepatic inflammation upon feeding an HFCD for 26 weeks (C) 2010 Elsevier Inc All rights reservedDiabetes mellitus: pathophysiological changes and therap

Effect of plasma triglyceride metabolism on lipid storage in adipose tissue: Studies using genetically engineered mouse models

The obesity epidemic is associated with an increased incidence of type 2 diabetes, cardiovascular morbidity and various types of cancer. A better insight into the molecular mechanisms that underlie adipogenesis and obesity may result in novel therapeutic handles to fight obesity and these associated diseases. Adipogenesis is determined by the balance between uptake of fatty acids (FA) from plasma into adipocytes, intracellular FA oxidation versus esterification of FA into triglycerides (TG), lipolysis of TG by intracellular lipases, and secretion of FA from adipocytes. Here, we review the mechanisms that are specifically involved in the entry of FA into adipose tissue. In plasma, these originating FA are either present as TG within apoB-containing lipoproteins (i.e. chylomicrons and VLDL) or as free FA bound to albumin. Kinetic studies, however, have revealed that TG are the major source of FA entering adipose tissue, both in the fed and fasted condition. In fact, studies with genetically engineered mice have revealed that the activity of lipoprotein lipase (LPL) is a major determinant for the development of obesity. As a general rule, high fat diet-induced adipogenesis is aggravated by stimulated LPL activity (e.g. by adipose tissue-specific overexpression of LPL or deficiency for apoCIII), and attenuated by inhibited LPL activity (e.g. by adipose-specific deficiency for LPL, overexpression of apoCI or angptl4, or by deficiency for apoE or the VLDL receptor). In addition, we describe that the trans-membrane transport of FA and cytoplasmic binding of FA in adipocytes can also dramatically affect adipogenesis. The relevance of these findings for human pathophysiology is discussed. © 2009 Elsevier B.V. All rights reserved

Rosiglitazone improves muscle insulin sensitivity, irrespective of increased triglyceride content, in ob/ob mice

Rosiglitazone improves muscle insulin sensitivity, irrespective of increased triglyceride content, in ob/ob mice. Muurling M, Mensink RP, Pijl H, Romijn JA, Havekes LM, Voshol PJ. TNO-Prevention and Health, Gaubius Laboratory, Leiden, The Netherland. The present study was performed to examine the effects of rosiglitazone treatment on tissue-specific insulin sensitivity. Therefore, we used obese, insulin-resistant ob/ob mice and measured the effects of rosiglitazone treatment on insulin sensitivity and simultaneously tissue-specific uptake of glucose and free fatty acids (FFA) under hyperinsulinemic euglycemic clamp conditions. Rosiglitazone treatment resulted in significantly higher body weight and decreased plasma levels of glucose, insulin, and triglyceride (TG). Glucose tolerance, as well as insulin sensitivity, was improved upon rosiglitazone treatment, as assessed by glucose tolerance and insulin sensitivity tests. Hyperinsulinemic euglycemic clamps showed increased glucose infusion rates with increased whole body insulin sensitivity. Rosiglitazone treatment resulted in increased glucose uptake by cardiac and skeletal muscle under hyperinsulinemic euglycemic clamp conditions, while no differences were observed in FA uptake. Measurement of TG content showed that rosiglitazone treatment resulted in decreased TG content of cardiac muscle, but increased TG content of skeletal muscle. We conclude that rosiglitazone treatment leads to strong improvement of insulin sensitivity, irrespective of increased muscle TG content, in ob/ob mice

Observational study on dietary changes of participants following a multicomponent lifestyle program (Reverse Diabetes2 Now)

Background Lifestyle intervention studies to treat type 2 diabetes (T2D) are on the rise. However, in-depth research is lacking into the dietary changes that participants make. Methods The present study aimed to observe the dietary intake of participants following the group program 'Reverse Diabetes2 Now' (RD2N) over 12 months. The web-based 24-h dietary recall-tool Compl-eat was used to collect dietary intake data. Results In total, 147 T2D patients were included in a cross-sectional study (n = 37 at baseline, n = 58 at 6 months, n = 52 at 12 months). A lower intake of total energy, carbohydrates and iodine was found for the groups at 6 and 12 months compared to the baseline group. The absolute consumption of total fat and saturated fat did not differ between the groups; only the percentage as total calorie consumption decreased. Consumption of vegetables and full-fat yoghurt was higher in groups at 6 and 12 months compared to the group at baseline. Consumption of bread, cakes and sweet biscuits, pasta/rice/tortillas, artificially sweetened soft drinks, and crisps were lower in the groups at 6 and 12 months compared to the group at baseline. Similar results were observed in a separate prospective study in 22 participants over 12 months following the same lifestyle-intervention. Conclusions Overall, participants shifted their dietary intake somewhat towards a healthier dietary pattern with overall lower energy and carbohydrates and more vegetables. Moreover, participants largely maintained this healthier pattern over 12 months. There were some concerns regarding iodine intake. These promising results need to be confirmed in a fully-scaled study, as well in a comparison with controls.Diabetes mellitus: pathophysiological changes and therap