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Diet induced inflammation of the hypothalamus in obesity chart – Attenuation of diet-induced hypothalamic inflammation following bariatric surgery in female mice

Science — Neuroinflammation and Depression: A Review.

Ethan Walker
Wednesday, May 18, 2016
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  • The mice swam 10 minutes on the first day, then add 10 minutes each day. Uematsu, and O.

  • Nature —6.

  • Assessment of different bariatric surgeries in the treatment of obesity and insulin resistance in mice. Keywords : age, obesity, hypothalamic oxidative stress, inflammation, AMPK activation.

  • Paraffin embedding of the liver and gastrocnemius muscle was performed in the same way as the brain tissue. C-reactive protein: a simple test to help predict risk of heart attack and stroke.

REVIEW article

Igarashi M, Guarente L. Proteins belonging to the hypothalamic nutrient sensing pathway were also modulated. Hypothalamic volumes were assessed by extracting the number of voxels for each side. Arruda, M. The prevalence of obesity is growing rapidly and has become a major public health problem worldwide [ 1 ].

Nevertheless, these factors do not significantly explain the ovesity of these two morbidities [ 7580 ]. Shin A. Review Series Free access In line with these results, swimming and diet can diminish not only hypothalamic inflammation, but also memory decline in an APOE4 mice model [ ]. Recent studies have revealed that the consumption of fat-rich foods can activate an inflammatory response in the hypothalamus, which disturbs the anorexigenic and thermogenic signals generated by the hormones leptin and insulin, leading in turn to anomalous body mass control.

In addition, a recent animal study indicated that high-fat diet-induced obesity can cause ILmediated activation of microglia in the hippocampus, impacting memory [ ]. Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise. Konrad D, Wueest S. The release of proinflammatory cytokines from microglia, astrocytes, perivascular macrophages, and infiltrating immune cells impairs neuronal function and translates into altered feeding behavior and energy expenditure. Furthermore, obesity-related systemic inflammation reduces the integrity of brain structures involved in reward and feeding behaviors

Aging Neurosci. On the other hand, autophagy is a protective mechanism which maintains hy;othalamus homeostasis and allows adaptation to environmental conditions. POMC neurons in the hypothalamus are the main targets of inflammation-induced apoptosis, resulting in an imbalance of the hypothalamic control of energy homeostasis 3558 This article has been cited by other articles in PMC. Physiol Rev. Physiol Behav. Hetz C.

Associated Data

Figure 6. FXR regulates many genes involved in hypothxlamus acid synthesis and lipid and lipoprotein metabolism [ 94 ]. The adipocyte as an endocrine cell. Moreover, accumulation of free fatty acids in obesity activates pro-inflammatory serine kinase cascades, such as I k B kinase and c-Jun N-terminal kinase, which in turn promotes adipose tissue to release IL-6 that triggers hepatocytes to synthesize and secrete CRP [ 25 ].

  • All chemicals were purchased from Sigma-Aldrich St.

  • Aging Neurosci. Mannan M.

  • Microglia play an active role in obesity-associated cognitive decline.

  • HFDs impair BBB function at the level of endothelial cells and astrocytes and also impair the transport function of hypothalamic tanycytes.

  • This increase was significantly different from the corresponding value in the CD group, from 3 weeks onward Figure 4C.

Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic acid pbesity patients with amyotrophic lateral sclerosis. Small pellets about mg of the dried homogenate were made and the body energy content was measured with the bomb calorimeter Parr Instruments Co. As mentioned earlier, many studies have focused on hypothalamic microglial inflammatory response due to the clear relation between the hypothalamus and energy homeostasis. Complications of IL-6 Circulating inflammatory mediators including IL-6 have been hypothesized to play a substantial role in the development and alteration of several diseases [ 30 — 32 ]. Image Anal.

Targeting these factors may provide effective approaches for therapies against associated metabolic perturbations. Furthermore, a reduction in parasympathetic tone has been demonstrated to contribute to the activation of inflammatory responses in obesity Horvath T. HFDs Induce a Systemic Chronic Low-Grade Inflammation Following the ingestion of HFDs, inflammation develops in the central nervous system CNS including the hypothalamus and in the peripheral tissues including the liver, adipose tissue, skeletal muscle, and intestine 6. Moreover, it has been hypothesized that systemic inflammation and augmented glucocorticoid levels can decrease serotonin availability in the brain, by changing the tryptophane catabolism pathway in favor of the production of kynurine rather than 5HT []. Moreover, autophagy appears defective or disrupted when associated either with high-fat diet-induced obesity [ 1250 ] or with hypothalamic inflammation [ 395960 ], respectively. Turnbaugh P.

Publication types

Metabolism — Passage of Cytokines across the Blood-Brain Barrier. High-fat diet. Metabolic processes are not regulated via neuronal cells alone, but rather they are embedded in a complex regulatory system of different cell types.

Here, we chose to evaluate cortical microglial activation, to expand on available knowledge on microglial immunometabolism in obesity outside of the hypothalamus. Presence of protein-bound unconjugated bile acids in the cytoplasmic fraction of rat brain. For GPR localization and signal transduction studies, 8 weeks lean rats were employed. The long-term high-fat diet can promote inflammation of the hypothalamic arcuate nucleus and induce systemic inflammation [ 19 ]. These data are in line with our observation on lipid metabolism; therefore, we selected another mitochondrial target, involved in FA metabolism.

Microglial cells from cerebral cortex were isolated for gene expression analysis using the Percoll isopycnic isolation, as it provides a high cell number Further strengths of our study include the large, well-characterized population-based sample size, a thorough methodological the hypothalamus combining a semi-automated segmentation algorithm with sensitive DTI metrics, along with confirmation analysis in an independent sample. Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images. Role of fish oil in human health and possible mechanism to reduce the inflammation. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Microglial glutamate uptake is coupled to glutathione synthesis and glutamate release. B Coregistration of the T1-weighted T1w -derived hypothalamus mask to the mean diffusivity MD image derived by diffusion-weighted imaging.

Exp Diabetes Res. Diet impact on mitochondrial bioenergetics and dynamics. Try out PMC Labs and tell us what you think. J Neurol. Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans.

Inflammation and Oxidative Stress in Obesity, Metabolic Syndrome, and Diabetes

Physiological functions of peroxisome proliferator-activated receptor beta. Basic Clin. Many methods have been used to detect hypothalamic inflammation. Aging Neurosci. Other dietary substances such as green tea polyphenol have been proposed as factors that reduce hypothalamic inflammation in obese models [ ].

Only trace amounts of LPS ranging from 0. Nature: Persistent microbiome alterations modulate the rate of post-dieting weight regain; Zhang et al. Using fluorescent microscopy, we found that, consistent with previous reports, chronic HFD-feeding resulted in a significant increase in arcuate microglia numbers Thaler et al. Ma et al.

Hetz C. These data underscore the strong effects of a HFD-induced changes on brain damage. Genetic and Molecular Aspects. POMC neurons in the hypothalamus are the main targets of inflammation-induced apoptosis, resulting in an imbalance of the hypothalamic control of energy homeostasis 3558 The hypothalamus controls a number of neuroendocrine functions that integrate metabolic feedback and regulate energy homeostasis 9 Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Lancet —

Tumor necrosis factor. The G-protein-coupled bile acid receptor, Gpbar1 TGR5negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells NF-kappaB in mice. It is believed that SIRT1 exerts a crucial role in aging-related hypothalamic dysfunction. Introduction Inflammation is an ordered sequence of events engineered to maintain tissue and organ homeostasis. Il1b showed daily rhythmicity under control conditions, which was maintained under obesogenic conditions with a shift in acrophase of 6 h see Table S2.

This could suggest a microglial metabolic switch to lipid substrate utilization in HFD-induced obesity. In parallel, while men had higher hypothalamus volumes than women and the volume of the left hemispheric hypothalamus was larger than the right, BMI was not associated with hypothalamic volume. Warnberg et al. PLoS One 4 Kreutzer, C.

To create the template, we applied the function buildtemplateparallel. Triscari, S. Puig, J. Mollica, M. ROS were quantified using dichlorofluorescein standard curve in dimethyl sulfoxide 0—1 mM.

  • Triscari, and A.

  • Nature —6. Over the last years, hypothalamic inflammation has been linked to the development and progression of obesity and its sequelae.

  • Hormone replacement therapy and interrelation between serum interleukin-6 and body mass index in postmenopause women: a population-based study. J Am Coll Cardiol.

  • Cell — Role of Glucocorticoids in the Regulation of Dopaminergic Neurotransmission.

Alvarez J. In addition, Bruce-Keller et al. Similar observations have also been observed in animal studies. Meanwhile, activated inflammatory macrophages M1 in plasma can reach the adipose and muscular tissues, pancreatic islets, and blood vessels, leading to peripheral inflammation 12 Neuropathology of Cognitively Normal Elderly. Passage of Cytokines across the Blood-Brain Barrier. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Studies have been showing that intake hypothalamus obesity a high-energy diet would induce metabolic disturbances and inflammation in the hypothalamus [ 2 ]. In the brain, microglia are oesity in maintaining brain homeostasis by surveying the environment, sensing invading pathogens and phagocyting dead neurons, and cellular debris, thus eliciting an innate immune response 56. Thiel Scientific Reports The author expresses sincere thanks to the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, for the use of the library. To create the template, we applied the function buildtemplateparallel. Higher body mass index is linked to altered hypothalamic microstructure.

Associated Data

In response to HFD feeding, hypothalamic astrocytes produce a variety of inflammatory factors. Escoll P. It is well established that along with the systematic inflammation, obesity is associated with neuroinflammation. In vivo and in vitro studies have shown that myofibroblasts and its induced fibrotic microenvironment are related to increased initiation and growth of breast cancer 99 ,

  • Trayhurn P, Wood I. Similar to the results in our study, Zhang et al.

  • Mechanisms Involved in Hypothalamic Inflammation As mentioned above, it is well established that diet-induced obesity is associated with hypothalamic inflammation.

  • All mice were sacrificed at 26 weeks of age. The EX group had the lowest body weight among three groups

  • Adiponectin and cardiovascular disease: state of the art? Therefore, we also evaluated the expression of key genes involved in microglial glucose, lipid, and glutamate metabolism.

  • Saturated fatty acids.

Adv Neurobiol. At the end of the protocol, mice were deeply anesthetized with ciet and then decapitated. While some studies reported that this inflammation-like response declined after several days of overnutrition, suggesting a compensatory mechanism to prevent neurons from damage 12others showed that gliosis and astrocytosis reoccurred after several weeks, pointing to prolonged changes in hypothalamic tissue and microstructural properties in obese animals 9. Thus, hypothalamic inflammation has been identified as a crucial step not only in the development of obesity but also in the aging processes, although the molecular mechanisms underlying the inflammatory response of hypothalamic neurons to obesity and aging is still partially unknown.

The Impact of Stress and Glucocorticoids on Memory. Rasgon N. Supplementation of Lactobacillus curvatus HY and Lactobacillus plantarum KY in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. In particular, intake of HFDs results in peripheral insulin resistance and obesity, resulting in the disruption of the blood-brain barrier. Metabolism —

According to research results, increased glucocorticoids levels can impair cognition. Physiological functions of peroxisome proliferator-activated receptor beta. These data obbesity that an altered serotoninergic system can influence the HPA axis. De Wit L. Ectopic lipid accumulation contributes additionally to the expression of proinflammatory mediators and the recruitment of M1 macrophages, thus aggravating systemic inflammation 26 Recent evidence suggests that obesity may cause hypothalamic inflammation.

Journal of Diabetes Research

ME, median eminence. Impaired leptin responsiveness in aged rats. Mice were individually housed and sham injected for 5 days with intraperitoneal i. Try out PMC Labs and tell us what you think.

Front Neurosci. High-fat diet induces the hypothalamic inflammation and inhibits the GnRH expression, altering hypothalamic outputs to hippocampus, amygdala, and reward-processing centers, which is disruption to cognitive function [ 41 ]. All chemicals were purchased from Sigma-Aldrich St. View Article Google Scholar 8. Fonken et al.

Bariatric surgery attenuates HFD-induced hypothalamic inflammation and microgliosis and restores leptin sensitivity, despite ongoing exposure to HFD. The same increase was observed to occur earlier at 3 weeks in the HFD group. J Clin Investig. However, methodology in the human studies remained unconvincing so far 182021 In addition, during the high-fat feeding, the mismatch between fatty acid uptake and utilization leads to the accumulation of toxic lipid species resulting in overproduction of ROS, insulin resistance, and inflammation.

Mol Cell. Click through the PLOS taxonomy to find articles in your field. In sum, animal experiments and first, but not all, human studies support the hypothesis that central homeostatic changes reflected in compromised micro structure of the hypothalamus are present in obesity. Thomas, K.

Consistently, human studies have hypothalakus HFD consumption with an increased risk of functional bowel symptoms 59such as inflammatory bowel diseases IBD As mentioned above, hypothalamic inflammation is detected within days in rats eating a high-fat diet [ 12 ], whereas in the same study, inflammation was not found in extra hypothalamic regions. Lindqvist A. The maternal diet affects hypothalamic function and plasticity, resulting in alterations to energy homeostasis in the offspring.

Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal HPA axis and influence monoaminergic systems. Importantly, these processes precede inflammatory events in peripheral tissues, such as the liver Nutr Cancer — This activation of hypothalamic inflammatory pathways results in the uncoupling of caloric intake and energy expenditure, fostering overeating and further weight gain.

  • Related articles.

  • All authors have read and agreed to the published version of the manuscript. Dutheil S.

  • Overall, these data suggest a small effect of the obesogenic diet on monocyte immunometabolism, suggesting that HFD specifically affects microglial immunometabolism.

  • Shivpuri et al. Myers MG Jr Leptin receptor signaling and the regulation of mammalian physiology.

Mechanisms Involved in Hypothalamic Inflammation As mentioned above, it is well established that diet-induced obesity hypothalams associated with hypothalamic inflammation. Key to this regulatory function is the melanocortin system, which consists of two functionally antagonistic neuronal populations — one subset of neurons expresses the orexigenic neuropeptides agouti-related peptide AgRP and neuropeptide Y NPYthe second subset expresses the anorexigenic peptides proopiomelanocortin POMC and cocaine and amphetamine regulated transcript CART. Bowers M. Therefore, regulation of macrophage A2bAR, either by genetic manipulations of monocytes or pharmacologically, may be a promising therapeutic approach. Interestingly, the use of probiotics improved the depression scale score [ ], thus providing evidence for the determinant role of gut microbiome in the pathogenesis of depression. This article has been cited by other articles in PMC. Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice.

De pbesity Monte S. Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. In support of this notion, a cohort of 1, subjects was selected and stratified in three groups i. More specifically, it has been proposed that the hypothalamus communicates directly with the subgenual cortex, which is considered to be implicated in the feeling of sadness []. Obesity induces inflammation not only in hypothalamus, but also in other brain areas, such as the hippocampus, affecting, thus, mood and memory.

Taken together, HFDs regulate bone metabolism and lead to osteoporosis partially through proinflammatory cytokines IL-6 and adipokines leptin. Cancer Prev Res. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. Nutr Res Rev.

Int J Biol Sci. Download references. Furthermore, IL-6 strongly stimulates hepatocytes to produce and secrete CRP, indicating a state of inflammation [ 23 ]. The dual response of protein kinase Fyn to neural trauma: early induction in neurons and delayed induction in reactive astrocytes. Paralleling these results, the hypothalamic expression levels of the orexigenic neuropeptide Agrp and the anorexic response of surgical mice to exogenous leptin were comparable to lean controls CD. Each degree of obesity was related directly to CRP, regardless of ethnicity characteristics and sex [ 82 ]. TLRs, especially TLR4, were shown to act as the receptor both for pathogens and saturated fatty acid [ 2829 ], giving rise to interaction between immune response and metabolic system.

Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after obesity chart restriction or resveratrol supplementation: a randomized trial. B, Four-week old male Wistar rats were fed for eight weeks induuced CT or HF diets and then submitted to intracerebroventricular icv cannulation. The novel object recognition memory: neurobiology, test procedure, and its modifications. Furthermore, coregistration failed in 3 subjects, resulting in participants eligible for MD analysis in sample n 1. In parallel, while men had higher hypothalamus volumes than women and the volume of the left hemispheric hypothalamus was larger than the right, BMI was not associated with hypothalamic volume.

A The changes in body weight of mice at weeks of age, respectively. Perusse and C. The role of microglia in central nervous system immunity and glioma immunology. The lower limit of detection was 1. Aurora Bracale, Dr.

  • Note the sparing of hypothalamus voxels which are affected by partial volume effects on the MD image arrows. Howard, B.

  • Lab Anim.

  • Our results confirm the lipotoxicity of HFD. Corresponding author.

  • This pathway is involved in nutrient sensing and cross-talks with hormone signaling systems to control neurotransmitter expression [33][37]. Polymorphism at the CRP locus influences gene expression and predisposes to systemic lupus erythematosus.

  • In addition, IL-1 and IL-6 when affected by stressors can cause further monoamine alterations [ ].

These results shed further light on microglial time-of-day innate immunometabolism in health and obesity. Ridker [ 78 ]. Try out PMC Labs and tell us what you think. Voevodskaya, O. Relation between abdominal subcutaneous fat tissue thickness and inflammatory markers during pregnancy. Prostaglandins Other Lipid Mediat.

Low-grade systemic inflammation related to a HFD resulted in cardiovascular complications partially through infiltration of adipose and vascular tissues by effector T cells Clin Transl Sci. The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update. Ectopic fat accumulation then led to the disruption of organelle homeostasis in the gastric mucosa, as evidenced by remarkable increases in the expression of LAMP2A the lysosomal markerCOX IV the mitochondrial markerCalnexin the ER markerand GM the Golgi marker in the gastric mucosa at 20 weeks Consistently, human studies have involved HFD consumption with an increased risk of functional bowel symptoms 59such as inflammatory bowel diseases IBD

  • These results suggest that the increase in energy intake observed in HFD animals may depend on the activation of the hypothalamic AMPK pathway. Wang, N.

  • Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. Nat Commun.

  • Accumulating evidence suggest that hypothalamus dysfunction is linked to aging metabolism, especially with early manifestations of Alzheimer's disease AD [ 17 ].

  • Downregulation of hypothalamic insulin receptor expression elicits depressive-like behaviors in rats. Popul Health Metr.

  • Huang S.

  • Institutional Review Board Statement Not applicable. Cell Metab.

When ER stress response is prolonged, the unfolded protein response fails, and an apoptotic response ensues [ ijflammation ]. Targeted genetic disruption of peroxisome proliferator-activated receptor-delta and colonic tumorigenesis. De Wit L. In: Martin C. Interestingly, the use of probiotics improved the depression scale score [ ], thus providing evidence for the determinant role of gut microbiome in the pathogenesis of depression. Associations of dietary fat with albuminuria and kidney dysfunction.

Papargyri P. Portovedo M. Alzheimers Dis. High-fat diet triggers an inflammatory response in the hypothalamus of rats [ 34 ].

Circulating mononuclear cells in the obese are in a proinflammatory state. About this article. Interleukin 6 Hypothalamu 6 is a cytokine produced by many different cell types, including immune cells and adipose tissue, that mediates inflammatory responses [ 7 ]. Taken together these data suggest an increased energy production in microglia of DIO animals during the light phase, which could be explained by an increased demand to sustain the increase in lipid metabolism. Bing C.

J Neuroinflamm. Both of these neuronal populations express high levels of receptors that bind hormones and thus respond to metabolic cues to control food intake and energy expenditure, depending on the energy state of the body 15 — J Nutr Health Aging — It has been recognized that obesity can promote myofibroblast differentiation within mammary adipose tissue, contributing to the microenvironment fibrotic remodeling and breast cancer progression Hypothalamic inflammation: a double-edged sword to nutritional diseases. Rahman M.

For example, after only 3 days gi bread slimming world diet HFD feeding, systemic insulin resistance, and glucose intolerance developed in mice Obesity is the major contributor to vascular dysfunction and inflammation in high-fat diet hypertensive rats. However, a recent study is challenging this view and shows that neurons, and not astrocytes, are the primary consumers of glucose Phone: Meanwhile, the PI3K pathway, the downstream of leptin receptor, was also decreased The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

The current Western lifestyle will increase the risk of fatty liver disease. Interplay between colonic inflammation and tachykininergic pathways in the onset of colonic dysmotility in a mouse model of diet-induced obesity. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Age Ageing. Alterations of the BBB are fundamentally involved in the development of hypothalamic inflammation

Therefore, we also evaluated the expression of key genes involved inflzmmation microglial glucose, lipid, and glutamate metabolism. Detection of serum lipids, SIRT1 and cytokines in serum Animal tissue sample were collected after the intervention. Sleep restriction was also correlated with cardiovascular diseases CVDbecause it was hypothesized to elevate CRP [ 90 ]. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters.

  • The optimal concentration of cDNA and primers, as well as the maximum efficiency of amplification, were obtained through five-point, two-fold dilution curve analysis for each gene.

  • These data underscore the strong effects of a HFD-induced changes on brain damage.

  • The mechanism underlying is possibly related to induction of central leptin and insulin resistance.

  • Front Endocrinol.

  • Unsaturated fatty acids can act either as nutrients or directly in the hypothalamus, reverting diet-induced inflammation and reducing body adiposity.

Several studies have shown that specific lipid species are linked with resistance to the main adipostatic hormones insulin and leptin in peripheral gi bread slimming world diet 40 — Interestingly, activation of TLR4 ifnlammation controls apoptotic activity of cells in the hypothalamus but subsequently activates proinflammatory pathways that ultimately lead to the development of central insulin and leptin resistance Circulating FFAs levels are strongly decreased without causing ectopic lipid accumulation in HFD-fed mice with dietary supplementation of Atglistatin, a selective inhibitor of adipose TG lipase, accompanied by decreased weight gain, insulin resistance, and liver diseases Furthermore, after comparing microbiota of obese vs. Depending on diet composition, cytokines are expressed in the hypothalamus, contributing to the activation of intracellular inflammatory signal transduction. Capuron L. Diet-induced obesity causes activation of cytokines and inflammatory pathways in the hypothalamus

Expecting that grey matter hypothalamus MD is smaller than MD in cerebrospinal fluid third ventricle 59average MD of obeeity diet induced inflammation of the hypothalamus in obesity chart third ventricle was chosen as a threshold for the hypothalamic MD. The limitation of this study is that we assessed the contribution of inflammation response to feeding behavior and obesity phenotype after DIO and DIO-R had already occurred. Currently, new approaches are underway that aim to disentangle the changes in diffusion metrics driven by blood perfusion originating from the extracellular space We additionally implemented a multi-atlas based label segmentation to validate our results in another independent sample.

Finally, we extracted the volume of the resulting hypothalamus segmentation and the ventricle-thresholded average MD values. C Comparison of 24 h identification index of mice in each group. Kullmann, S. Received Feb 26; Accepted Apr

  • Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: A combined immunohistochemical and magnetic resonance imaging study. Using a dier multimodal MRI approach in two large samples of healthy adults of the general population, we were able to demonstrate that a higher BMI specifically relates to higher MD in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities.

  • Therefore, inflammatory pathways in the brain may already be primed toward a proinflammatory response as a consequence of maternal diet.

  • Russell et al. According to a previously study [17]these levels of LPS do not interfere with the results.

  • Mol Neurobiol. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus.

  • According to a recent meta-analysis, hair cortisol level is positively associated with anthropometric features such as BMI and waist-to-hip ratio [ ].

Physiology — RBCs-produced NO can contribute to the intravascular NO pool and suppression of platelet aggregation, thus regulating vascular homeostasis Jacka F. Mastorakos P. Konrad D, Wueest S. There is also an interplay between these neurotransmitters and the HPA axis.

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The results showed that hypothalamic inflammation, glial cells activation and cognition decline were induced by high-fat diet. The presently reported difference in time-of-day expression of microglial cytokine genes, is in line with our previous results The role of adiponectin in cancer: a review of current evidence. Elevated SIRT1 activity can prevent endothelial cell from death and delay endothelial cell senescence [ 26 ]. J Clin Endocrinol Metab.

  • Download references. Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy.

  • Furthermore, obese patients with metabolically unhealthy profile have higher risk of depression, compared with obese ones with metabolically healthy profile [ 79 ].

  • This highlights the sensitivity and specificity of our procedure and compares to previous high-quality segmentation protocols implemented in smaller sample sizes 1319 ,

  • Ceramide is a common mediator of cellular stress, and inhibition of ceramide biosynthesis blocks the ability of SFAs to induce insulin resistance in obese rodent models A transient, early inflammatory phase and, with sustained exposure to high-fat diet HFDa secondary phase, in which prolonged inflammatory cascades lead to the activation of cellular stress mechanisms.

  • Curr Obes Rep.

Armougom F. Osteoblasts and adipocytes are derived from the same mesenchymal stem cell MSC source 66leading to interactions between osteoclastogenesis and adipogenesis that can be affected by dietary fat intake Cancer Res. Lindqvist A. Perspect Med.

Since the molecular mechanisms linking the HFD administration to the inflammatory response inf,ammation hypothalamic level is not completely known, we studied the effect of long-term high-fat feeding on the activation of AMPK in the hypothalamus. Limitations and strengths Some limitations need to be taken into consideration. Obesity results from an imbalance between energy intake and expenditure, which means a positive energy balance [ 12 ]. GFAP: 3.

Collectively, inducer inflammatory and stress response pathways are rapidly activated during HFD-feeding and promote the development of neuronal insulin and leptin resistance, raising the possibility that nutrient excess itself is the primary driver of hypothalamic inflammation. Both of these neuronal populations express high levels of receptors that bind hormones and thus respond to metabolic cues to control food intake and energy expenditure, depending on the energy state of the body 15 — Thus, inflammation in the arcuate nucleus, as is the case in some obese patients, can influence the input and output signals to other brain regions, affecting, thus, cognition and mood [ 58 ] Figure 2. Cai D, Liu T. Song C.

Ribeiro, E. Hotamisligil GS. J Chem Neuroanat. Bray and B. Obesity is associated with hypothalamic injury in rodents and humans. Get the most important science stories of the day, free in your inbox. According to a previously study [17]these levels of LPS do not interfere with the results.

  • Biochem Biophys Res Commun.

  • Recently, work from our lab has shown that acute HFD feeding leads to reduced brain glucose uptake.

  • Currently, bariatric surgery has emerged as the most effective obesity treatment available in both magnitude and durability of its effects Mingrone et al. Nat Rev Neurosci.

  • Evaluation of daily rhythmicity of Cd36 gene expression confirms this observation, with a loss of rhythm under obesogenic conditions see Table S2.

  • Beyer, G.

Impaired leptin responsiveness in aged rats. Further studies will be needed to define the cellular and molecular mechanisms underlying these effects, but such studies are likely to reveal important insights into the nature of hypothalamic inflammation and uncover novel targets for the non-surgical treatment of obesity. Ricci R, Bevilacqua F. Insulin concentrations were significantly elevated in HFD-fed animals during the dark phase active period at ZT18, which could indicate an impaired insulin sensitivity, as glucose concentrations during this period were not elevated, but overall maintained during 24 h Figure 2E.

Stalder T. As discussed above, epidemiological data provide evidence that obesity often occurs in association with mood and cognitive disorders. High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents. Zheng P. High fat diet promotes achievement of peak bone mass in young rats. Age Ageing.

ORIGINAL RESEARCH article

The macrophage A2b adenosine receptor regulates tissue insulin sensitivity. Along with the monoaminergic systems, the neurotransmitters GABA gamma-amino butyric acid and glutamate acid contribute in the pathophysiology of depression [ ]. Shintani F. Davami M.

Keywords: diet, obesity, hypothalamic inflammation, cognitive disorders, mood disorders, depression, diet induced inflammation of the hypothalamus in obesity chart. Conclusions As discussed above, epidemiological data provide evidence that obesity often occurs in association with mood and cognitive disorders. Glucose is primarily taken up by astrocytes located around blood vessels and metabolized to lactate, which is supplied to neurons A study using diffusion tensor imaging reported obesity-associated hypothalamic damage associated with inflammatory markers and worse cognitive performance Key to this regulatory function is the melanocortin system, which consists of two functionally antagonistic neuronal populations — one subset of neurons expresses the orexigenic neuropeptides agouti-related peptide AgRP and neuropeptide Y NPYthe second subset expresses the anorexigenic peptides proopiomelanocortin POMC and cocaine and amphetamine regulated transcript CART. Insulin action and resistance in obesity and type 2 diabetes. Lee BC, Lee J.

Hepatol Commun. Fermented green tea dlet alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice. The proposed mechanisms leading to obesity-induced hypothalamic inflammation discussed above are presented in Table 1. Abstract Over the last years, hypothalamic inflammation has been linked to the development and progression of obesity and its sequelae. Pedditzi E.

Rudel, and J. Prevalence of high C-reactive protein in persons with serum lipid concentrations within recommended values. Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis.

  • Froy O.

  • Williams L. Shifts in gut microbiota populations activate Toll-like receptor TLR signaling pathway, leading to increased intestinal permeability to endotoxins [such as lipopolysaccharides LPS ] and thus promoting the translocation of LPS to the circulation 10 —

  • Then, the registration matrix was used to coregister the MD images to the anatomical space.

  • Howard, B. Increased serum C-reactive protein level in Japanese patients of psoriasis with cardio- and cerebrovascular disease.

  • Swimming exercise relieves the peripheral and central inflammation, but the mechanism has not been investigated extensively to date. Further, experimental and genetic interventions that block the hypothalamic NF- B signaling reversed hypothalamic insulin and leptin resistance and was associated with reduced food intake and weight loss in the high-fat-induced obesity [ 17 ].

Evaluation of the effect of smoking on complete blood counts, serum C-reactive protein and magnesium levels in healthy adult male smokers. TG values were higher at diet induced inflammation of the hypothalamus in obesity chart, 12, and 18 weeks than at 1 and 3 weeks in the CD group while, in the HFD group, these values increased progressively with age. TLRs are pattern-recognition receptors which provide the first line of host defense, and four members of the TLR family including TLR1, 2, 4, and 6, are reported to recognize lipid containing motifs [ 1213 ]. Conclusion In summary, chronic high-fat diet HFD results in upregulation of inflammatory markers and proliferation of microglia within the mediobasal hypothalamus.

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This study compared hypothalamic inflammation between high-fat diet-induced obese and obese-resistant rats and their responses charr chow food intervention. NK performed the monocyte isolation and helped with the animal experiments. Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus. Cell Biol. During the following 8 weeks, changing the diet to standard chow from high-fat diet reduced the weight gain in DIO rats but not in DIO-R rats Figure 1 b.

Skip to main content Thank you for visiting nature. Neuron — ECL was developed after secondary antibody was shaken at room temperature for 1 h. CAS Google Scholar. Western blot WB analysis An appropriate amount of lysate was added to the tissue. Aging Albany NY. Nat Neurosci 9: —

In light of the limited knowledge of metabolic inflammation in the human brain, further neuroimaging studies on human patients are needed to validate findings from animal models and potential inflammstion strategies. In line with these results, recent meta-analyses indicate that anti-inflammatory factors, such as NSAIDs and cytokine inhibitors, can be safely used in the treatment of major depressive disorders or symptoms []. Markers of hypothalamic inflammation increase significantly during the first days of HFD feeding, with reactive gliosis and neuronal injury manifesting during the first week, even prior to body weight gain Engin A.

Introduction

Due to its small size, minor shifts fiet artifacts within the overlay of hypothalamus and the MD mask might be detrimental for analysis, especially for hypothalamic and non-hypothalamic voxels adjacent to the third ventricle Fig. Within-run variations for all measurements fall in the range suggested by the manufacturers. Published : 24 October

Research results support that obesity induces Th17 cells differentiation [ ]. Alzheimers Dement. High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity. High-fat diet can induce ERS in hypothalamus, promoting inflammation [ 40 ]. Gupta S. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes. Leptin resistance has been associated with the atypical subtype of major depression [ ].

Semin Immunol. Availability of data and materials All other data is available from the corresponding author upon request. Influence of roux-en-Y gastric bypass on plasma bile acid gi bread slimming world diet a comparative study between rats, pigs and humans. It has been shown that hypercaloric environment induces a proinflammatory response in the hypothalamus via NF-kB and toll-like receptor activation, leading to disturbed energy homeostasis 9 — Unlike other cytokines, IL-6 is unusual in that its major effects take place at sites distinct from its origin and are consequent upon its circulating concentrations. It has been shown that FA treatment of BV2 cells a microglial cell line is a potent inducer of cytokine production via TLR4 signaling, thus leading to low-grade inflammation even in the absence of immune challenge

Sarvottam and Yadav [ 34 ]. The reduction of hypothalamic inflammation hyypothalamus obesity corrects simultaneously feeding, thermogenesis and metabolic disarrangements, placing this phenomenon in a central position in the pathogenesis of obesity [4][5][8]. Comparison of adiponectin, leptin and blood lipid levels in normal and obese postmenopause women. GM and MM contributed to the discussion and to the editing of the manuscript. Adiponectin suppression of highglucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. A reproducible evaluation of ANTs similarity metric performance in brain image registration.

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A decrease in the discrimination index DI suggests that the mice's tne memory and learning ability are impaired [ 50 ]. After each swimming training session, wipe off the water from the mice as soon as possible, dry the fur, clean the swimming pool, and return them to the original cage. J Clin Invest.

  • Rats were divided into two experimental groups according to a different dietary regimen: the first group control diet, CD received a standard diet

  • Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Find articles by Jais, A.

  • Similar to previous reports, we found that weight loss associated with diet reversal was also associated with increased expression of Agrp Yu et al.

  • Sotiropoulos I.

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Potential Prevention of Mood and Cognitive Disorders by Treating Hypothalamic Inflammation As discussed above, it is well established that obesity can induce hypothalamic inflammation. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Family history, APOE4 genotype, depression, hypertension, vascular factors, dyslipidemia, obesity, DM, insulin ov, and traumatic brain injury have also been established as risk factors for AD [ 22232425 ]. ER stress and the UPR are potent regulators of POMC neurons and are therefore interesting targets for the amelioration of central insulin and leptin resistance and the regulation of metabolic disorders. Le Bras A. Additionally, changes in the function of glucocorticoid receptors GRs type II which bind glucocorticoids that disrupt the HPA axis negative feedback are responsible for HPA axis dysregulation and high cortisol concentrations in depressed patients [, ].

  • Simerly 3Naji N. Dewey, B.

  • Sci Rep.

  • Adiponectin Adiponectin is a protein hormone derived from obestiy that has gained considerable importance due to its positive impacts on inflammation [ 99 ], atherosclerosis, type 2 diabetes mellitus T2DMand insulin resistance [ 99 — ]; thus, it links the adipose tissue directly with the cornerstones of metabolic abnormalities [ ].

  • Similar findings were obtained in inflamation study, showing that HFDs could promote intestinal tumor progression in genetically susceptible K-ras G 12 Dint mice in the absence of obesity but based on marked alterations in gut bacterial communities Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance.

  • Neuroprotection by a bile acid in an acute stroke model in the rat.

  • Arch Dermatol Res.

Furthermore, glucagon-like peptide 1 GLP-1 receptor agonists are widely used for the treatment of obesity and DM. Epidemiological evidence has suggested inducwd obesity HFDs promotes obesity, which is closely associated with lower bone mineral density BMD and a higher risk of osteoporotic fractures 68 — Escoll P. These cells have long processes that bridge the cerebrospinal fluid to the portal capillaries. Sotiropoulos I. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Moreover, this pathway promotes the inflammatory response in microglia cells, which are the resident macrophage cells of hypothalamus [ 39 ].

The assay for CuZn—SOD was based on its ability to inhibit the oxidation of oxymine by the xanthine—xanthine oxidase system Oyanagui, Fas expression in microglia from HFD-fed animals showed a lower expression at the end of the dark phase and higher expression at the beginning of the light phase, compared to control chow-fed animals Figure 5I. Avants, B. PubMed Abstract Google Scholar. Adiponectin and incident coronary heart disease and stroke. Baroncini, M. Therefore, the effects of HFD seem to start in the hypothalamus and affect peripheral tissues only after prolonged consumption of fat Thaler et al.

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