Objective: NONcNZO10 (NZ10) mice are predisposed to obesity and develop type 2 diabetes (T2D) and hepatic steatosis even when maintained on a control diet (CD) of 6% fat. Studies were designed to determine whether this extreme susceptibility phenotype could be alleviated by diet and if so the molecular targets of diet.
Methods: NZ10 and SWR/J (SWR) control mice were fed a CD or a test diet of high protein and fish oil (HPO) for 19 weeks and then analyzed for steatosis, blood chemistry, hepatic gene and micro-RNA expression.
Scope: To characterize diet-dependent miRNA profiles and their targets in the visceral adipose of mice with polygenic susceptibility to type 2 diabetes.
Methods And Results: Six-week NONcNZO10/LtJ (NZ10) and control SWR/J mice were subjected to high protein-fish oil or control diets for 19 weeks and micro-RNA microarray analyses were implemented on visceral adipose RNA. We found that 27 miRNAs were significantly induced and 10 significantly repressed in the VA of obese NZ10 mice compared with controls.
Objective: An intimate association exists between oxidative stress and inflammation. Because adipose tissue (AT) inflammation is intricately linked to metabolic disorders, it was hypothesized that reducing oxidative stress would be effective in ameliorating AT inflammation in obesity.
Methods: Wild-type mice were fed a high-fat diet (HF) for 8 weeks followed by a 2-week treatment with nanoformulated copper/zinc superoxide dismutase (NanoSOD).
Objective: Adipose tissue (AT) macrophages mediate AT inflammation in obesity, and cyclooxygenase-2 (COX-2) is a major inflammatory gene. It was hypothesized that deletion of hematopoietic COX-2 will inhibit AT inflammation in obesity.
Methods: Lethally irradiated wild-type (WT) mice were injected with bone marrow (BM) cells collected from WT or COX-2 knock-out (COX-2-/-) donor mice and fed a high-fat diet for 16 weeks.
Visceral adipose tissue (VAT) is a source of inflammatory cytokines that in obese subjects may contribute to low-level systemic inflammation and development of metabolic syndrome. Expansion of VAT involves adipocyte hyperplasia and hypertrophy and requires breakdown of the extracellular matrix and increased vascular outgrowth. To investigate changes of gene expression associated with VAT expansion and the role of combined genetics and diet, we implemented gene microarray analyses of VAT in NONcNZO10 (NZ10) and control SWR/J mice subjected to control chow (CD) or a diet of high protein and fish oil (HPO).
View Article and Find Full Text PDFBackground: Diet and exercise promote cardiovascular health but their relative contributions to atherosclerosis are not fully known. The transition from a sedentary to active lifestyle requires increased caloric intake to achieve energy balance. Using atherosclerosis-prone ApoE-null mice we sought to determine whether the benefits of exercise for arterial disease are dependent on the food source of the additional calories.
View Article and Find Full Text PDFBrief periods of ischemia do not damage the heart and can actually protect against reperfusion injury caused by extended ischemia. It is not known what causes the transition from protection to irreversible damage as ischemia progresses. c-Jun N-terminal kinase-1 (JNK-1) is a stress-regulated kinase that is activated by reactive oxygen and thought to promote injury during severe acute myocardial infarction.
View Article and Find Full Text PDFBackground: Idiopathic Parkinson disease (PD) is a multi-system disorder with a multifactorial etiology and diverse clinical phenotype. Selective, regional dopaminergic neuronal degeneration in the substantia nigra and other CNS areas including the amygdala are observed in all patients. Apoptotic mechanisms resulting from oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of the disease.
View Article and Find Full Text PDFForensic Sci Int
September 2009
Excited delirium (ED) syndrome is a serious medical condition associated with acute onset of agitated violent behavior that often culminates in a sudden unexplained death. While the contribution of restraint, struggle and the use of conductive energy devices (CED) to the cause and manner of death raise controversy, a CNS dysfunction of dopamine signaling may underlie the delirium and fatal autonomic dysfunction. We conducted a mortality review for a case series of ninety excited delirium deaths and present results on the association of a 2-protein biomarker signature.
View Article and Find Full Text PDFIn Parkinson's disease (PD) neuronal degeneration is associated with abnormal protein aggregation in various forms including Lewy bodies (LBs). A major component of LBs is alpha-synuclein; septin 4 (SEPT4), a polymerizing GTP-binding protein that serves as scaffold for diverse molecules has been found to colocalize with alpha-synuclein in LBs. The central role of SEPT4 in the etiopathogenesis of PD has been suggested since SEPT4 also shows a physiological association with alpha-synuclein and serves as a substrate for parkin.
View Article and Find Full Text PDFMutations in the leucine-rich repeat kinase 2 (LRRK2) gene, especially the G2019S mutation, have been identified as a common cause of Parkinson's disease in southern European and other Mediterranean populations (Iberians, Ashkenazi Jews and North African Arabs). Owing to the geographic and historic vicinity of Greece with areas of high prevalence of LRRK2 mutations we studied the frequency of the G2019S mutation in a well characterized cohort of familial and sporadic Parkinson's disease patients of Greek origin from mainland Greece. The prevalence of the LRRK2 R1441C mutation and the G2385R Asian polymorphism was also determined.
View Article and Find Full Text PDFAlpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers.
View Article and Find Full Text PDFThe chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine "rush". Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition.
View Article and Find Full Text PDFBackground: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Most cases are sporadic but about 10-15% of patients have a positive family history of PD.
Objective: To compare clinical phenotypes between familial (fPD) and sporadic (sPD) PD patients.