The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation

<p>Abstract</p> <p>Background</p> <p>This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines.</p> <p>Methods</p> <p>Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 groups (control, colitis, HFD and colitis + HFD).</p> <p>Results</p> <p>Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group.</p> <p>Conclusion</p> <p>Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.</p

Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice

Objective: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. Methods: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. Results: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gammaaminobutyric acid levels, as compared with unseparated controls. Conclusion: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.This work was supported in part by National Institutes of Health (NIH) research grant 5R01HD053131, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH Office of Dietary Supplements, and Brazilian grants from CNPq and CAPES (Grant # RO1 HD053131). The authors would like to thank Dr. Patricia Foley for veterinarian technical support and Dr. Jose Paulo Andrade for the excellent comments and suggestions to improve this manuscript. N.S. contributed with the stereological studies. I.L.F. and R.B.O. contributed with the behavioral studies. I.L.F., R.B.O., and R.L.G. contributed with the study design, study analysis, and manuscript preparation. G.A.M. and P.B.F. contributed with neurochemical brain analyses. J.I.A.L. and G.M.A. contributed with hormonal and CRP serum analyses. D.G.C., K.M.C., and R.S.R. contributed with animal experimentation and data collection

The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques

Nephrolog

Methylmercury Interactions With Gut Microbiota and Potential Modulation of Neurogenic Niches in the Brain

Mercury (Hg) is a well-recognized biohazard for the nervous system. Methylmercury (MeHg) is an organic methylated form of Hg, highly toxic to humans, targeting the brain, as MeHg is rapidly absorbed, and easily reaches and crosses the blood-brain barrier (Takahashi et al., 2017). Neurological symptoms may vary from acute motor and visual effects to marked behavioral and psychiatric alterations. At higher neurotoxic levels, MeHg can lead to irreversible coma and, ultimately, death. It has been highlighted that MeHg long-term and low-grade toxicity may be associated with neurodegenerative disorders and perhaps a direct causality for Alzheimer’s disease (Siblerud et al., 2019). Although MeHg harmful effects to the brain have been thoroughly documented in the literature, such as increased oxidative stress and mitochondrial dysfunction, halted glutamate uptake by astrocytes and overt glutamate excitotoxicity, and activation of neuronal apoptosis cascades (Antunes dos Santos et al., 2016), less is known how MeHg affects the hippocampal neurogenic niche. Hence, in this opinion paper, we summarize up-to-date literature addressing MeHg effects on the intestinal microbiota, a key player influencing MeHg bioavailability and MeHg induction of intestinal dysbiosis (and vice-versa), and related intricate mechanisms during homeostasis and disease states. In addition, we discuss possible ways how MeHg may affect hippocampal neurogenesis and the potential lasting consequences for brain neurodegeneration.FEDER-CENTRO 2020- CENTRO-01-0145-FEDER-000012 (HealthyAging 2020) and COMPETE and FCT (POCI-01-0145-FEDER- 029221 and UIDB/04539/2020), Pest-C/SAU/UI3282/2013-2014 and CNC.IBILI UID/NEU/04539/2013 with national funds PT2020/COMPETE 2020 and FCT/FUNCAP (POCTI-FEDER- 02/SAICT/2017/31699), Brazilian CAPES-PROCAD (071/2013 # 88881.068408/2014-01) and CNPq-PVE grant

The Transition From Undernutrition to Overnutrition Under Adverse Environments and Poverty: The Risk for Chronic Diseases

Nutritional transition is an important public health issue in developing countries, where switch from undernutrition to overnutrition/obesity is rapidly occurring, often within two or three generations. Such transition is related to changes in lifestyle, with people having more access to western high-caloric diets. In developing countries, settings of poverty, poor sanitation and hygiene are still common, where children are exposed to numerous enteric pathogens, pollutants, and other biohazards. Populations living under such adverse environments and facing the nutritional transition may have increased risks for chronic illnesses in later life, including diabetes, cardiovascular, and neurodegenerative diseases. This opinion paper summarizes novel findings and recent literature addressing the nutrition transition under adverse environments, including the gut microbiota-brain axis dysfunction and their lasting effects with deleterious consequences for later development

Loss of SR-A and CD36 activity reduces atherosclerotic lesion complexity without abrogating foam cell formation in hyperlipidemic mice

The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated Apoe(-/-) mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks. We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in Apoe(-/-)Cd36(-/-)Msr1(-/-) mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to Apoe(-/-) mice. However, Apoe(-/-)Cd36(-/-)Msr1(-/-) lesions showed reduced expression of inflammatory genes and morphological analysis revealed a approximately 30% decrease in macrophage apoptosis and a striking approximately 50% decrease in plaque necrosis in aortic root lesions of these mice. Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in Apoe(-/-) mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stabilit