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Objective: Neuropsychiatric symptoms are frequent in obese individuals. Mounting evidence suggests that adiposity-related inflammation contributes to this effect. This study assessed the relationship between adiposity, neuropsychiatric symptom dimensions and systemic inflammation in subjects stratified by body-mass-index (BMI)., Methods: The study included 165 subjects, of whom 70 were very severely obese (BMI ≥ 40 kg/m 2 ), 50 severely obese (BMI: 35-39.99 kg/m 2 ), 21 overweight or moderately obese (BMI: 25-34.9 kg/m 2 ), and 24 lean (BMI < 25 kg/m 2 ). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mini-International Neuropsychiatric Interview (MINI). Fatigue and general neurobehavioral symptoms were assessed using the Multidimensional Fatigue Inventory (MFI) and Neurotoxicity Rating Scale (NRS) respectively. Serum levels of the inflammatory markers, high-sensitive (hs) CRP and hsIL-6, were determined by ELISA., Results: Severely obese subjects exhibited higher MADRS, MFI and NRS scores and were more frequently afflicted with current diagnosis of major depression than lean participants. Scores on psychometric scales were also increased in very severely obese subjects, although to a lesser extent. Alterations in neuropsychiatric dimensions were highly inter-related. HsCRP was significantly increased in subjects with severe or very severe obesity, while hsIL-6 was augmented in all obese groups. Overall, increased neuropsychiatric comorbidity was associated with greater systemic inflammation, notably hsCRP., Conclusion: Obesity is characterized by an increased prevalence of inter-related neuropsychiatric symptoms together with low-grade systemic inflammation augmenting with adiposity. The association between adiposity, systemic inflammation and neuropsychiatric alterations supports the contribution of adiposity-related inflammatory processes to neuropsychiatric comorbidities in obesity. These data suggest that consideration of adiposity characteristics may help identifying subjects at increased risk for neuropsychiatric comorbidity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. This study aimed to investigate alterations in KYN and microbiota-mediated indole routes of TRP metabolism in obese subjects relatively to non-obese controls and to determine their relationship with systemic inflammation. Methods: Eighty-five obese adults (avg. BMI = 40.48) and 42 non-obese control individuals (avg. BMI = 24.03) were recruited. Plasma levels of TRP catabolites were assessed using Ultra High Performance Liquid Chromatography-ElectroSpray-Ionization-Tandem Mass Spectrometry. High-sensitive C-reactive protein (hsCRP) and high-sensitive interleukin 6 (hsIL-6) were measured in the serum as markers of systemic inflammation using enzyme-linked immunosorbent assay. Results: Both KYN and microbiota-mediated indole routes of TRP metabolism were altered in obese subjects, as reflected in higher KYN/TRP ratio and lower 5-HT and indoles levels, relatively to non-obese controls. HsIL-6 and hsCRP were increased in obesity and were overall associated with TRP metabolic pathways alterations. Conclusion: These results indicate for the first time that KYN and indole TRP metabolic pathways are concomitantly altered in obese subjects and highlight their respective associations with obesity-related systemic inflammation., (Copyright © 2020 Cussotto, Delgado, Anesi, Dexpert, Aubert, Beau, Forestier, Ledaguenel, Magne, Mattivi and Capuron.)

Although the high prevalence of anxiety in obesity increasingly emerges as significant risk factor for related severe health complications, the underlying pathophysiological mechanisms remain poorly understood. Considering that chronic inflammation is a key component of obesity and is well known to impact brain function and emotional behavior, we hypothesized that it may similarly contribute to the development of obesity-related anxiety. This hypothesis was experimentally tested by measuring whether chronic food restriction, a procedure known to reduce inflammation, or chronic anti-inflammatory treatment with ibuprofen improved anxiety-like behavior and concomitantly decreased peripheral and/or hippocampal inflammation characterizing a model of severe obesity, the db/db mice. In both experiments, reduced anxiety-like behaviors in the open-field and/or elevated plus-maze were selectively associated with decreased hippocampal tumor necrosis factor-α (TNF-α) mRNA expression. Highlighting the causality of both events, chronic central infusion of the TNF-α blocker etanercept was then shown to be sufficient to improve anxiety-like behavior in db/db mice. Lastly, by measuring the impact of ex-vivo etanercept on hippocampal synaptic processes underlying anxiety-like behaviors, we showed that the anxiolytic effect of central TNF-α blockade likely involved modulation of synaptic transmission within the ventral hippocampus. Altogether, these results uphold the role of brain TNF-α in mediating obesity-related anxiety and provide important clues about how it may modulate brain function and behavior. They may therefore help to introduce novel therapeutic strategies to reduce anxiety associated with inflammatory conditions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Obesity is a major public health burden associated with neuropsychiatric comorbidities leading to social and occupational impairment. Given the growing prevalence of both obesity and mental disorders worldwide, understanding the risk factors of obesity-related neuropsychiatric comorbidities is crucial to develop preventive strategies and individualized treatments. Recent findings suggest that adiposity-driven inflammation contributes to neuropsychiatric comorbidities in obesity. However, not all obese subjects afflicted with chronic inflammation develop neuropsychiatric symptoms, suggesting additional risk factors. The aim of this study was to investigate the impact of personal history of major depressive disorder (MDD) on obesity-related inflammation and neuropsychiatric symptoms, and their relationship. A case-control study was conducted comparing 66 obese patients (body mass index > 35 kg/m 2 ) and 22 healthy non-obese participants, free of any current neuropsychiatric diseases including MDD. Neuropsychiatric symptoms were assessed using the Neurotoxicity Rating Scale (NRS). Sociodemographic and clinical variables were gathered and blood was collected for the measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP). Multiple regression analyses were performed to assess the contribution of obesity and personal history of MDD to clinical outcomes and inflammatory status in study participants. Hs-CRP levels as well as NRS scores were significantly increased in the obese group. Overall, personal history of depression accounted for increased NRS scores but no significant association was found with inflammatory status. In addition, history of depression did not significantly modulate the relationship of obesity-related inflammation with NRS scores. Interestingly, obese individuals with history of recurrent MDD (n = 13) exhibited higher scores in the cognitive and sickness symptoms dimensions of the NRS compared to obese subjects with history of one depressive episode only. Findings indicate that history of depression contributes to neuropsychiatric symptoms, but not to systemic inflammation, in obese subjects free of current depressive episode. These results provide relevant information on the risk factors that may help identify obese subjects with increased risk of neuropsychiatric comorbidity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recent reports suggest that the risk of depressive symptoms in obesity is potentiated in subjects presenting a metabolically unhealthy phenotype. Inflammation is often considered a defining criteria of metabolic health. However, this factor may drive the association of metabolic health with depressive symptoms given its well-known role in the pathophysiology of depression. This study aimed at determining the relative contribution of inflammation and metabolic abnormalities to depressive symptoms in obesity., Methods: One-hundred severely obese adults (BMI ≥ 35-40 kg/m 2 ) and 25 non-obese control individuals (BMI < 30 kg/m 2 ) were recruited. Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and Mini-International Neuropsychiatric Interview (MINI). Serum high-sensitive C-reactive protein (hs-CRP) was measured as a marker of systemic inflammation. Metabolically unhealthy obesity was defined as obesity associated with two or more metabolic alterations, including low high-density lipoprotein cholesterol, hypertriglyceridemia, high fasting glucose and hypertension., Results: Total MADRS scores were significantly higher in obese subjects with significant inflammation (hs-CRP ≥ 5 mg/L) compared to those with low inflammation (hs-CRP < 5 mg/L) and non-obese controls. Interestingly, hs-CRP levels significantly predicted MADRS scores in the whole population under study and in the group of obese subjects. Overall, no association was found between MADRS scores and individual metabolic alterations or the composite measure of metabolically unhealthy obesity. Similarly, the association of hs-CRP with MADRS scores in obese patients was not modulated by metabolic health factors., Conclusions: These results indicate that systemic inflammation represents a stronger contributor of obesity-related depressive symptoms than metabolic health per se. This supports the notion that inclusion of inflammation in the definition of metabolically unhealthy obesity drives the association found between poor metabolic health and depressive symptoms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Context: Inmates, notably women, are at greater risk for obesity and metabolic complications than the general population according to several studies from high income countries. Data regarding French correctional institutions are lacking so far. To fill this gap, we have assessed in a sample from a French prison (33 females and 18 males) the gender-specific effect of incarceration on weight and body mass index (BMI) and examined their current metabolic status. Furthermore, to reveal the possible determinants of increased obesity, we analyzed emotional vulnerability, eating behavior and physical activity using self-reported questionnaires., Results: In this sample, obesity (BMI≥30 kg/m2) was already frequent in women (18.2%) but rather scarce for men (11%) at prison entry. Incarceration worsened the rate of obesity in both genders (21.2% and 16.7% respectively). At the time of study, abdominal obesity estimated through waist circumference was particularly prevalent in women (69.7%) versus men (27.8%) and metabolic syndrome was detected in 33% of female against none in male inmates. Abdominal obesity was associated with female sex (p<0.03), low physical activity (p<0.05) and eating disorder (p = 0.07) in univariate analyses. Low physical activity remained significant as an explanatory factor of higher abdominal obesity in multivariate analysis. A marked difference between genders was found for practice of physical activity with a higher proportion of women compared to men being inactive (37.9% vs. 11.8%) and fewer women being very active (17.2% vs. 41.2%)., Conclusion: This study revealed that a significant proportion of women of this correctional institution combined established obesity, a metabolic syndrome and very little practice of physical activity which put them at high risk of cardiovascular disease. Thus, obesity should be better surveyed and treated in prison, especially for female inmates. Increased physical activity, adapted to obese women, would be the first mean to decrease obesity and gender differences., Competing Interests: The authors have declared that no competing interests exist.

Impairment in cognitive flexibility and set shifting abilities has been described in obesity. This alteration is critical as it can interfere with obesity management strategies. Recent evidences suggest that chronic low-grade inflammation may be involved in cognitive deficits associated with obesity, but the potential involvement in reduced flexibility remains unknown. The objective of this study was to assess the contribution of low-grade inflammation, determined by circulating levels of high-sensitivity C-reactive protein (hsCRP), in reduced cognitive flexibility and shifting abilities of obese subjects relatively to a group of non-obese participants. Performance in the intra/extra-dimensional set shift (IED) test, extracted from the CANTAB, was assessed in 66 obese subjects and 20 non-obese participants. Obese subjects with concentrations of hsCRP above 5mg/L exhibited reduced performance on the IED test in comparison to obese subjects with lower levels of hsCRP and non-obese participants. This difference was particularly manifest in the number of errors made during the extra-dimensional shift (EDS errors). In contrast, performance before the extra-dimensional shift was spared. Linear regression analyses revealed that the association between obesity and IED alterations was significant only when the condition hsCRP >5mg/L was entered in the model. These findings are important as they indicate that, rather than obesity itself, low-grade inflammation represents a major contributor of IED performance in obese subjects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence during adolescence is particularly alarming since recent evidence indicates that obesity can affect hippocampal function during this developmental period. Adolescence is a decisive period for maturation of the amygdala and the hypothalamic-pituitary-adrenal (HPA) stress axis, both required for lifelong cognitive and emotional processing. However, little data are available on the impact of obesity during adolescence on amygdala function. Herein, we therefore evaluate in rats whether juvenile high-fat diet (HFD)-induced obesity alters amygdala-dependent emotional memory and whether it depends on HPA axis deregulation. Exposure to HFD from weaning to adulthood, i.e., covering adolescence, enhances long-term emotional memories as assessed by odor-malaise and tone-shock associations. Juvenile HFD also enhances emotion-induced neuronal activation of the basolateral complex of the amygdala (BLA), which correlates with protracted plasma corticosterone release. HFD exposure restricted to adulthood does not modify all these parameters, indicating adolescence is a vulnerable period to the effects of HFD-induced obesity. Finally, exaggerated emotional memory and BLA synaptic plasticity after juvenile HFD are alleviated by a glucocorticoid receptor antagonist. Altogether, our results demonstrate that juvenile HFD alters HPA axis reactivity leading to an enhancement of amygdala-dependent synaptic and memory processes. Adolescence represents a period of increased susceptibility to the effects of diet-induced obesity on amygdala function., (Copyright © 2015 the authors 0270-6474/15/354092-12$15.00/0.)

Context: The inflammatory state of the adipose tissue is believed to contribute to systemic low-grade inflammation in obesity., Objective: This study assessed the relationship between adipose and circulating inflammatory markers as well as the influence of adipose inflammation on bariatric surgery-induced weight reduction., Design: This was a cross-sectional and longitudinal study (up to 14 mo)., Setting: The study was conducted in the digestive/bariatric surgery department of the Tivoli and Jean Villar clinics, Bordeaux, France., Patients: Thirty-seven obese patients [body mass index (BMI)>35-40 kg/m2)] seeking bariatric surgery were included. Twenty-eight of them were successively followed up at 1-3 months after surgery and 25 between 6 and 14 months after surgery., Main Outcome Measures: Fasting serum samples were collected before surgery to assess concentrations of inflammatory markers. Samples of visceral adipose tissue were extracted during surgery and gene expression of cytokines and immune cell markers were evaluated using quantitative RT-PCR. Pre- and postsurgery weight and BMI were collected., Results: Gene expression of several cytokines were strongly intercorrelated in the visceral adipose tissue. Adipose expression of macrophage and T cell markers were related to adipose expression of TNF-α and IL-1 receptor antagonist (P<.01) and to systemic levels of TNF-α (P<.01) and IL-6 (P<.05). A higher inflammatory state of the adipose tissue predicted a lower BMI reduction after surgery (P<.05), notably at early stages after surgery., Conclusions: These findings support the involvement of macrophages and T cells in adipose inflammation and provide new information regarding the role of the visceral adipose tissue in the inflammatory state of obesity and its impact on obesity treatment outcomes, such as surgery-induced weight loss.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and is characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50–60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines and C-reactive protein (CRP). As pharmacotherapy fails in at least 30–40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further efforts directed at implementing these strategies in clinical practice could contribute to improved outcomes in patients with depression, comorbid obesity, and/or metabolic dysregulation. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms are frequent in obesity. In addition to their substantial economic and health impact, these symptoms significantly interfere with the quality of life and social function of obese individuals. While the pathophysiological mechanisms underlying obesity-related neuropsychiatric symptoms are still under investigation and remain to be clearly identified, there is increasing evidence for a role of inflammatory processes. Obesity is characterized by a chronic low-grade inflammatory state that is likely to influence neuropsychiatric status given the well-known and highly documented effects of inflammation on brain activity/function and behavior. This hypothesis is supported by recent findings emanating from clinical investigations in obese subjects and from experimentations conducted in animal models of obesity. These studies converge to show that obesity-related inflammatory processes, originating either from the adipose tissue or gut microbiota environment, spread to the brain where they lead to substantial changes in neurocircuitry, neuroendocrine activity, neurotransmitter metabolism and activity, and neurogenesis. Together, these alterations contribute to shape the propitious bases for the development of obesity-related neuropsychiatric comorbidities. [ABSTRACT FROM AUTHOR]

The ability of cytokines to influence cerebral functions and to induce the development of behavioral alterations is well established in conditions of acute or chronic high-grade activation of the innate immune system. Recent evidence suggests that the release of these immune mediators during chronic low-grade endogenous inflammatory processes may also contribute to the development of behavioral alterations. Metabolic disorders, including obesity, type 2 diabetes and the metabolic syndrome, represent examples of those conditions which are both characterized by a chronic low-grade inflammatory state and an increased prevalence of behavioral disorders. In metabolic disorders, the increased production of acute-phase proteins and cytokines (e.g. C-reactive protein, interleukin-6 and tumor necrosis factor-α), but at relatively low levels, may promote and contribute to the development of behavioral symptoms, including depressive symptoms, cognitive impairment, fatigue, sleep problems and pain. This hypothesis is supported by a growing literature referring both to experimental and clinical findings that will be reviewed here. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed “inflammageing”. The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the “inflamed” phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted. [ABSTRACT FROM AUTHOR]

Alterations in endocrine functions and low-grade systemic inflammation represent fundamental characteristics of obesity. These biological systems have been repeatedly linked to fatigue symptoms. The aim of the study was to assess the relationship between fatigue dimensions and metabolic/inflammatory markers in a sample of non-diabetic obese children. The possibility that inflammation-induced alterations in tryptophan metabolism relates to specific dimensions of fatigue was also investigated in a subsample of patients. The study was conducted in 41 obese children, median aged 12 [9–15] years, recruited in a pediatric tertiary center. Three dimensions of fatigue (e.g., general fatigue, sleep/rest, cognitive fatigue) were assessed using the Pediatric Quality of Life Inventory Multidimentional Fatigue Scale. In addition, a principal component analysis was performed to identify fatigue dimensions that were specific to the population under study. This analysis extracted five relevant dimensions corresponding respectively to concentration, energy, self-perceived cognitive efficiency, sleep/rest and motivation/anhedonia. Blood samples were collected for the measurement of inflammatory and metabolic markers, including high sensitivity C-reactive protein (hs-CRP), insulin, uricemia and glycaemia. Tryptophan, kynurenine and neopterin levels were also determined in a subsample of 17 patients. In the whole population under study, cognitive fatigue and reduced motivation/anhedonia were associated with BMI, independently of sex and age. The dimension of reduced motivation/anhedonia was associated with insulin resistance and inflammatory biomarkers. The association with insulin resistance persisted when the extent of fat mass (BMI-SDS) was taken into account. No association was found between tryptophan metabolism and specific dimensions of fatigue, but kynurenine and the kynurenine/tryptophan ratio correlated with insulin and HOMA-IR. These data indicate that insulin resistance in non diabetic obese children is associated with both cognitive fatigue and reduced motivation/anhedonia and with alterations in tryptophan metabolism. Further investigations are needed to determine whether inflammation-induced alterations in tryptophan metabolism is directly or indirectly implicated in insulin resistance and related fatigue. [ABSTRACT FROM AUTHOR]

• Obese subjects exhibited reduced serum fasting levels of ghrelin when compared to non-obese control subjects. • Activation in dorsolateral prefrontal cortices during non-food reward processing was greater in obese subjects. • Significant associations were found between reduced ghrelin levels and slower post-reward choices. • Reward-related hyperactivity in dorsolateral prefrontal cortices correlated with reduced ghrelin levels. While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency. Fifteen severely obese subjects (BMI > 35 kg/m2) and fifteen healthy non-obese control subjects (BMI < 30 kg/m2) were recruited. A guessing-task paradigm, previously shown to activate the ventral striatum, was used to assess reward-related brain neural activity by functional magnetic resonance imaging (fMRI). Fasting blood samples were collected for the measurement of circulating ghrelin. Significant activations in the ventral striatum, ventromedial prefrontal cortex and extrastriate visual cortex were elicited by the fMRI task in both obese and control subjects. In addition, greater reward-related activations were present in the dorsolateral prefrontal cortex, and precuneus/posterior cingulate of obese subjects compared to controls. Obese subjects exhibited longer choice times after repeated reward and lower circulating ghrelin levels than lean controls. Reduced ghrelin levels significantly predicted slower post-reward choices and reward-related hyperactivity in dorsolateral prefrontal cortices in obese subjects. This study provides evidence of association between circulating ghrelin and reward-related brain activity in obesity and encourages further exploration of the role of ghrelin system in altered eating behavior in obesity. [ABSTRACT FROM AUTHOR]