Omega-3 Fatty Acids Reduce Adipose Tissue Macrophages in Human Subjects with Insulin Resistance

Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides. This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of ω-3 fatty acids on adipocytes and macrophages in vitro. Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks. Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged. The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment. Adipose and muscle ω-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin. In vitro, M1-polarized macrophages expressed high levels of MCP-1. The addition of ω-3 fatty acids reduced MCP-1 expression with no effect on TNF-α. In addition, ω-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages. Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity. Diabetes 62:1709–1717, 201

Seismic evidence for large-scale compositional heterogeneity of oceanic core complexes

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q08002, doi:10.1029/2008GC002009.Long-lived detachment faults at mid-ocean ridges exhume deep-seated rocks to form oceanic core complexes (OCCs). Using large-offset (6 km) multichannel seismic data, we have derived two-dimensional seismic tomography models for three of the best developed OCCs on the Mid-Atlantic Ridge. Our results show that large lateral variations in P wave velocity occur within the upper ~0.5–1.7 km of the lithosphere. We observe good correlations between velocity structure and lithology as documented by in situ geological samples and seafloor morphology, and we use these correlations to show that gabbros are heterogeneously distributed as large (tens to >100 km2) bodies within serpentinized peridotites. Neither the gabbros nor the serpentinites show any systematic distribution with respect to along-isochron position within the enclosing spreading segment, indicating that melt extraction from the mantle is not necessarily focused at segment centers, as has been commonly inferred. In the spreading direction, gabbros are consistently present toward the terminations of the detachment faults. This suggests enhanced magmatism during the late stage of OCC formation due either to natural variability in the magmatic cycle or to decompression melting during footwall exhumation. Heat introduced into the rift valley by flow and crystallization of this melt could weaken the axial lithosphere and result in formation of new faults, and it therefore may explain eventual abandonment of detachments that form OCCs. Detailed seismic studies of the kind described here, when constrained by seafloor morphology and geological samples, can distinguish between major lithological units such as volcanics, gabbros, and serpentinized peridotites at lateral scales of a few kilometers. Thus such studies have tremendous potential to elucidate the internal structure of the shallow lithosphere and to help us understand the tectonic and magmatic processes by which they were emplaced.This research was supported by grants from the U.S. NSF-IODP Program

Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD

Pioglitazone Treatment Reduces Adipose Tissue Inflammation through Reduction of Mast Cell and Macrophage Number and by Improving Vascularity

<div><p>Context and Objective</p><p>Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.</p><p>Design, Setting and Participants</p><p>Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.</p><p>Results</p><p>Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm² (p = 0.02) in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.</p><p>Conclusion</p><p>The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.</p></div

Variations in Management of Mild Prenatal Hydronephrosis Among Maternal-Fetal Medicine Obstetricians, and Pediatric Urologists and Radiologists

Purpose: There are no current guidelines for diagnosing and managing mild prenatal hydronephrosis. Variations in physician approach make it difficult to analyze outcomes and establish optimal management. We determined the variability of diagnostic approach and management regarding prenatal hydronephrosis among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. Materials and Methods: Online surveys were sent to mailing lists for national societies for each specialty. Participants were surveyed regarding criteria for diagnosing mild prenatal hydronephrosis and recommendations for postnatal management, including use of antibiotic prophylaxis, followup scheduling and type of followup imaging. Results: A total of 308 maternal-fetal medicine obstetricians, 126 pediatric urologists and 112 pediatric radiologists responded. Pediatric urologists and radiologists were divided between Society for Fetal Urology criteria and use of anteroposterior pelvic diameter for diagnosis, while maternal-fetal medicine obstetricians preferred using the latter. For postnatal evaluation radiologists preferred using personal criteria, while urologists preferred using anteroposterior pelvic diameter or Society for Fetal Urology grading system. There was wide variation in the use of antibiotic prophylaxis among pediatric urologists. Regarding the use of voiding cystourethrography/radionuclide cystography in patients with prenatal hydronephrosis, neither urologists nor radiologists were consistent in their recommendations. Finally, there was no agreement on length of followup for mild prenatal hydronephrosis. Conclusions: We observed a lack of uniformity regarding grading criteria in diagnosing hydronephrosis prenatally and postnatally among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. There was also a lack of agreement on the management of mild intermittent prenatal hydronephrosis, resulting in these cases being managed inconsistently. A unified set of guidelines for diagnosis, evaluation and management of mild intermittent prenatal hydronephrosis would allow more effective evaluation of outcomes