Long-term obesity is associated with depression and neuroinflammation

Lorena, Fernanda Beraldo; Nascimento, Bruna Pascarelli Pedrico do; Camargo, Esther Lopes Ricci Adari; Bernardi, Maria Martha; Fukushima, André Rinaldi; Panizza, Julia do N.; Nogueira, Paula de B.; Brandão, Marllos Eduardo; Ribeiro, Miriam O.

doi:10.20945/2359-3997000000400

Cited by 11 publications

(12 citation statements)

References 102 publications

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“…Studies using diet-induced obesity models demonstrated a significant increase in inflammatory markers in the frontal cortex, such as tumour necrosis factor α (TNF-α) and interleukin-1 β (IL-1β), 72 and also demonstrated that HFD-induced obesity could cause a harmful influence on brain cortex bioenergetics. 73 Obese humans with high BMI (in particular, over 40) and without neurological diseases have reduced mRNA expression of the anti-inflammatory cytokine interleukin 10 (IL-10) and increased mRNA expression of the enzyme associated with cytotoxicity and apoptosis inducible nitric oxide synthase in the frontal cortex. 74 These alterations, especially associated with the dysregulation of pro- or anti-inflammatory cytokines, may indicate an intensified neuroinflammatory response in this brain region.…”

Section: Discussionmentioning

confidence: 99%

Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

Andrade

Fernandes

Forny-Germano

et al. 2023

Brain Communications

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Obesity is defined as abnormal or excessive fat accumulation that may impair health and is a risk factor for developing other diseases, such as type 2 diabetes and cardiovascular disorder. Obesity is also associated with structural and functional alterations in the brain, and this condition has been shown to increase the risk of Alzheimer’s disease. However, while obesity has been associated with neurodegenerative processes, its impact on brain cell composition remains to be determined. In the current study, we used the isotropic fractionator method to determine the absolute composition of neuronal and non-neuronal cells in different brain regions of the genetic mouse models of obesity Lepob/ob and LepRNull/Null. Our results show that 10 to 12-month-old female Lepob/ob and LepRNull/Null mice have reduced neuronal number and density in the hippocampus compared to C57BL/6 wild-type mice. Furthermore, LepRNull/Null mice have increased density of non-neuronal cells, mainly glial cells, in the hippocampus, frontal cortex and hypothalamus compared to wild-type or Lepob/ob mice, indicating enhanced inflammatory responses in different brain regions of the LepRNull/Null model. Collectively, our findings suggest that obesity might cause changes in brain cell composition that are associated with neurodegenerative and inflammatory processes in different brain regions of female mice.

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Section: Discussionmentioning

confidence: 99%

Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

Andrade

Fernandes

Forny-Germano

et al. 2023

Brain Communications

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“…Interestingly, the protective effect of MED on depressive symptoms was noted to gradually decrease as BMI increased. The prevalence of depression is known to be increased in the setting of obesity, a condition that promotes inflammation as well as resistance to insulin and leptin (43,44). Thus, a combination of MED adherence and proper weight control is guaranteed to improve the effectiveness of MED adherence in regard to alleviating depression.…”

Section: Discussionmentioning

confidence: 99%

Non-linear association between Mediterranean diet and depressive symptom in U.S. adults: A cross-sectional study

et al. 2022

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The Mediterranean diet (MED), a dietary pattern rich in fruits and vegetables, whole grains, legumes, nuts, fish, and olive oil, has anti-oxidative and anti-inflammatory effects. Although some data suggest that MED adherence is associated with decreased manifestation of depressive symptoms, it remains necessary to further analyze this apparent non-linear association as well as the influence of different factors on the relationship between MED and depression. Here, we investigated associations between the alternate MED (aMED) score and depressive symptom via multivariate logistic regression, weighted generalized additive (GAM) and two-step linear regression models, analyzing data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). The most important factor relevant to aMED score that contributed to the prevalence of depressive symptom was assessed using random forest. Furthermore, we examined whether the relationship between aMED score and depressive symptom differs by age, race, sex, socioeconomic variables, lifestyle- and health-related variables, and chronic medical conditions, via subgroup analyses. A total of 19,477 participants (20–80 years of age) were included in this cross-sectional study. In crude and adjusted (1–5) multivariate logistic regression models, increased aMED score was noted to associate with non-depressive status, as defined using the Patient Health Questionnaire-9 (P < 0.05). Data analyses via GAM and two-piecewise linear regression revealed a non-linear association between aMED and depressive symptom, which had an inflection point of 3. Random forest results revealed that vegetable score contributes greatest to the relationship between aMED and depressive symptom. Subgroup analyses revealed that aMED score is significantly negatively related with depressive symptom in most different populations (P < 0.05) with the exception of high annual income, diabetes, borderline blood glucose level and Parkinson's disease (PD) (P > 0.05). In conclusion, we observed a non-linear association between aMED score and depressive symptom. Further studies are needed to validate our results.

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“…The cerebral cortex, also called gray matter, is the brain’s outermost layer, which plays a key role in many high-level functions, such as reasoning, emotion, problem solving, memory, language, and consciousness. Some studies have also demonstrated that HFD-induced obesity activates neuroinflammation mechanisms with harmful effects on the cerebral cortex [ 98 , 99 , 100 ].…”

Section: Obesity Induces Cognitive Declinementioning

confidence: 99%

Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes

Schmitt

Gaspar

2023

Metabolites

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Obesity is defined as abnormal and excessive fat accumulation, and it is a risk factor for developing metabolic and neurodegenerative diseases and cognitive deficits. Obesity is caused by an imbalance in energy homeostasis resulting from increased caloric intake associated with a sedentary lifestyle. However, the entire physiopathology linking obesity with neurodegeneration and cognitive decline has not yet been elucidated. During the progression of obesity, adipose tissue undergoes immune, metabolic, and functional changes that induce chronic low-grade inflammation. It has been proposed that inflammatory processes may participate in both the peripheral disorders and brain disorders associated with obesity, including the development of cognitive deficits. In addition, mitochondrial dysfunction is related to inflammation and oxidative stress, causing cellular oxidative damage. Preclinical and clinical studies of obesity and metabolic disorders have demonstrated mitochondrial brain dysfunction. Since neuronal cells have a high energy demand and mitochondria play an important role in maintaining a constant energy supply, impairments in mitochondrial activity lead to neuronal damage and dysfunction and, consequently, to neurotoxicity. In this review, we highlight the effect of obesity and high-fat diet consumption on brain neuroinflammation and mitochondrial changes as a link between metabolic dysfunction and cognitive decline.

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Long-term obesity is associated with depression and neuroinflammation

Cited by 11 publications

References 102 publications

Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

Non-linear association between Mediterranean diet and depressive symptom in U.S. adults: A cross-sectional study

Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes

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