Obesity is a major public health problem that predisposes to several diseases and higher mortality in patients with COVID-19. Obesity also generates neuroinflammation, which predisposes to the ...development of neuropsychiatric diseases. Since there is a lack of effective treatments for obesity, the search for new strategies to reverse its consequences is urgent. In this perspective, the anti-inflammatory properties of omega-3 polyunsaturated fatty acids such as DHA/EPA might reduce the harmful effects of obesity. Here, we used the cafeteria diet (CAF) model to induce obesity in Wistar rats. Animals received ultra-processed food for 20 weeks, and DHA/EPA supplementation (500 mg/kg per d) was performed between the 16th and the 20th week. At the end of the experiment, it was evaluated: body weight, visceral fat deposition, plasma glucose, insulin and triglycerides, and it was also measured the levels of inflammatory cytokines TNF-α and IL-6 in plasma and liver, and TNF-α in the prefrontal cortex. The elevated plus maze test was performed to analyse anxiety-like behaviour. Our results demonstrated that DHA/EPA could not reverse weight and fat gain and did not modify plasma dosages. However, there was a decrease in IL-6 in the liver (DHA/EPA effect: P = 0.023) and TNF-α in the brain (CAF compared with CAF + DHA/EPA, P < 0.05). Also, there was a decrease in the anxiety index in CAF + DHA/EPA compared with the CAF group (P < 0.01). Thus, DHA/EPA supplementation is helpful to reverse the consequences of obesity in the brain.
Since the first studies of the nervous system by the Nobel laureates Camillo Golgi and Santiago Ramon y Cajal using simple dyes and conventional light microscopes, microscopy has come a long way to ...the most recent techniques that make it possible to perform images in live cells and animals in health and disease. Many pathological conditions of the central nervous system have already been linked to inflammatory responses. In this scenario, several available markers and techniques can help imaging and unveil the neuroinflammatory process. Moreover, microscopy imaging techniques have become even more necessary to validate the large quantity of data generated in the era of ‘omics’. This review aims to highlight how to assess neuroinflammation by using microscopy as a tool to provide specific details about the cell’s architecture during neuroinflammatory conditions. First, we describe specific markers that have been used in light microscopy studies and that are widely applied to unravel and describe neuroinflammatory mechanisms in distinct conditions. Then, we discuss some important methodologies that facilitate the imaging of these markers, such as immunohistochemistry and immunofluorescence techniques. Emphasis will be given to studies using two‐photon microscopy, an approach that revolutionized the real‐time assessment of neuroinflammatory processes. Finally, some studies integrating omics with microscopy will be presented. The fusion of these techniques is developing, but the high amount of data generated from these applications will certainly improve comprehension of the molecular mechanisms involved in neuroinflammation.
Microscopy allows the assessment of cell targets in a spatiotemporal manner. Therefore, it can integrate a large amount of data from omic methods and provide information considering the morphology and location of cells. Important advances in the field of neuroinflammation have been possible due to advances in microscopy techniques.
Obesity has been linked to cognitive decline and adverse effects on brain health. Zinc (Zn) is a mineral with important metabolic functions that can modulate obesity-related neurological impairment. ...Thus, the present study aimed to evaluate the effects of 12 weeks of Zn supplementation on the inflammatory profile, cognitive function, and mood of overweight or obese women through a double-blind, placebo-controlled study. The study included 42 women aged between 40 and 60, randomly divided into two groups: Zn supplementation (30 mg/day) or placebo for 12 weeks. Data regarding sociodemographic, anthropometric, dietary, and physical activity were collected. Mini-mental state examination (MMSE), verbal fluency test, clock drawing test, and Stroop test were performed. Anxiety and depression symptoms were assessed using the Beck anxiety inventory and the BDI-II, respectively. Saliva samples were collected to evaluate IL-1β, IL-6, TNF-α, insulin, nitrite, and Zn levels. Of the 42 participants (mean age 49.58 ± 6.46 years), 32 were included in the study analyses. Changes in body weight and macronutrient consumption were not different between placebo and Zn supplementation groups. Cognitive scores on the MMSE and Stroop tests were higher in the Zn supplementation group than in the placebo group. Salivary levels of IL-1b and Zn increased in the Zn group compared to placebo. There was no significant change in the adjusted means of the BDI-II and BECK scores between the zinc vs. placebo groups. Twelve weeks of Zn supplementation was able to partially improve the cognitive scores assessed in overweight or obese women, regardless of weight loss. These findings suggest that Zn supplementation can be considered an adjunct strategy to enhance cognitive health in overweight or obese women.
Rates of obesity have been growing at alarming rates, compromising the health of the world population. Thus, the search for interventions that address the metabolic repercussions of obesity are ...necessary. Here we evaluated the metabolic and antioxidant effects of zinc and branched-chain amino acids (BCAA) supplementation on obese rats. Male Wistar rats were fed either a high-fat/high-fructose diet (HFD) or a standard diet (SD) for 19 weeks. From the fifteenth week until the end of the experiment, HFD- and SD-fed rats received zinc (6 mg/kg) or BCAA (750 mg/kg) supplementation. Body weight, abdominal fat, lipid profile, blood glucose, insulin, leptin, and hepatic transaminases were evaluated. In the liver, superoxide dismutase and catalase activities and lipid peroxidation were also analyzed. HFD-fed animals showed increased weight gain, abdominal fat pad, plasma insulin, leptin, and triglycerides levels in comparison with SD-fed rats. Zinc supplementation reduced all these parameters, suggesting a beneficial role for the treatment of obesity. BCAA, on the other hand, did not show any beneficial effect. Liver antioxidant enzymes and hepatic transaminases plasma levels did not change among groups. Lipid peroxidation was higher in HFD-fed rats and was not reverted by zinc or BCAA supplementation. In conclusion, zinc supplementation may be a useful strategy for the treatment of the metabolic dysfunction associated with obesity.
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Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cafeteria diet (CAF) mimics human Western diet and has been used in animal models to study obesity. The purpose of this study is to demonstrate that our CAF model induces metabolic disorder related ...to obesity and affects recognition memory in Wistar rats. We also compared the intake of two different soft drinks, as part of the CAF, on recognition memory. Our results demonstrate that CAF-fed rats increased weight gain and visceral adiposity, and exhibited hyperglycemia, hypertriglyceridemia, high leptin and low insulin plasma levels. Moreover, CAF animals showed higher lipid peroxidation in the liver and developed non-alcoholic fatty liver disease. Surprisingly, the group fed with cola-based soft drinks presented an improvement in recognition memory, whereas animals fed with orange-based soft drinks showed worse performance in this task. Our data indicates that CAF induces obesity and affects recognition memory, but the composition of the diet interfere when the neurological function is evaluated.
Zinc (Zn) plays an important role in metabolic homeostasis and may modulate neurological impairment related to obesity. The present study aimed to evaluate the effect of Zn supplementation on the ...intestinal microbiota, fatty acid profile, and neurofunctional parameters in obese male Wistar rats. Rats were fed a cafeteria diet (CAF), composed of ultra-processed and highly caloric and palatable foods, for 20 weeks to induce obesity. From week 16, Zn supplementation was started (10 mg/kg/day). At the end of the experiment, we evaluated the colon morphology, composition of gut microbiota, intestinal fatty acids, integrity of the intestinal barrier and blood–brain barrier (BBB), and neuroplasticity markers in the cerebral cortex and hippocampus. Obese rats showed dysbiosis, morphological changes, short-chain fatty acid (SCFA) reduction, and increased saturated fatty acids in the colon. BBB may also be compromised in CAF-fed animals, as claudin-5 expression is reduced in the cerebral cortex. In addition, synaptophysin was decreased in the hippocampus, which may affect synaptic function. Our findings showed that Zn could not protect obese animals from intestinal dysbiosis. However, an increase in acetate levels was observed, which suggests a partial beneficial effect of Zn. Thus, Zn supplementation may not be sufficient to protect from obesity-related dysfunctions.
Neuroinflammation is a consequence of overeating and may predispose to the development of cognitive decline and neurological disorders. This study aimed to evaluate the impact of omega-3 ...supplementation on memory and neuroinflammatory markers in rats fed a high-fat diet. Male Wistar rats were divided into four groups: standard diet (SD); standard diet + omega-3 (SD + O); high fat diet (HFD); and high fat diet + omega-3 (HFD + O). Diet administration was performed for 20 weeks and omega-3 supplementation started at the 16th week. HFD significantly increased body weight, while omega-3 supplementation did not modify the total weight gain. However, animals from the HFD + O group showed a lower level of visceral fat along with an improvement in insulin sensitivity following HFD. Thus, our results demonstrate a beneficial metabolic role of omega-3 following HFD. On the other hand, HFD animals presented an impairment in object recognition memory, which was not recovered by omega-3. In addition, there was an increase in GFAP-positive cells in the cerebral cortex of the HFD group, showing that omega-3 supplementation can be effective to decrease astrogliosis. However, no differences in GFAP number of cells were found in the hippocampus. We also demonstrated a significant increase in gene expression of pro-inflammatory cytokines IL-6 and TNF-α in cerebral cortex of the HFD group, reinforcing the anti-inflammatory role of this family of fatty acids. In summary, omega-3 supplementation was not sufficient to reverse the memory deficit caused by HFD, although it played an important role in reducing the neuroinflammatory profile. Therefore, omega-3 fatty acids may play an important role in the central nervous system, preventing the progression of neuroinflammation in obesity.
•Maternal obesity alters the neurological and behavioral phenotype in the offspring.•Treatment with cannabidiol rescues anxiety and social disturbances in the offspring.•Both perinatal maternal ...obesity and CBD present sexually dimorphic influences.•CBD modulates glial reactivity, oxytocin, glutamate and endocannabinoid signaling.
Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.
Probiotic supplementation has been identified as a potential target to reduce inflammatory mediators associated with obesity. Therefore, this study assessed the effect of probiotic
LB1.5 on ...anxiety-like behavior, gene expression in the prefrontal cortex, and neuroinflammation in the cerebral cortex and hippocampus of male mice fed a high-fat diet. Mice aged 21 days were divided into four groups: control (CONT), control plus probiotic (CONT + PROB), high-fat diet (HFD), and high-fat diet plus probiotic (HFD + PROB), and fed for 13 weeks. The probiotic
1.5 (3.1 × 108 CFU/mL, derived from raw buffalo milk) was administered by gavage three times a week. Probiotic supplementation provided an anxiolytic effect in CONT and HFD. The IL-6 showed lower levels after probiotic supplementation in the HFD. Regarding immunoreactivity for GFAP in the cerebral cortex, we demonstrated that animals HFD-fed had a reduction in cells number compared to CONT. In the hippocampus, we found an interaction between diet and supplementation, as well as an effect of probiotic supplementation. A higher number of Th positive cells was observed in the cerebral cortex in mice fed HFD.
LB1.5 supplementation decreased serum IL-6 levels in HFD-fed mice and promoted a reduction in anxiety-like behavior.
The implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during ...pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed.
Here we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats.
We have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1β in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to
neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes.
Together, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.
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