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Link Examined Between High-Fat Diet and Depression: The Impact of Obesity and Fat Intake on Mental H



Research on Diet Quality and DepressionWhile a poor diet may be associated with risk of depression, studies are still assessing whether quality of diet causes depression or worsens existing symptoms. Dietary patterns that have been examined and are thought to influence risk of depression include those high in ultra-processed foods, saturated fat (including high-fat dairy or fried foods), processed meat, refined grains and added sugars including sugar-sweetened beverages.


Researchers suspect the benefits of a healthful diet relative to depression risk could be attributed to factors including improvements in vascular health, lower levels of LDL cholesterol, lower inflammatory levels, less oxidative stress, improvements in neurotransmitters serotonin and norepinephrine or improvements in the gut microbiome.




Link Examined Between High-Fat Diet and Depression




Food Insecurity and Depressive SymptomsFood insecurity can lead to inadequate intake of nutrients, which can affect mental health and depression and increase risk for chronic disease, especially among women in the United States. Studies also show that food access issues are linked to depression. One cross-sectional study of 372 older adults found those with food insecurity had less ability to care for themselves and, in turn, had higher depressive symptoms, as well as poorer diets.


B vitaminsA systematic review and meta-analysis of B-vitamin supplementation and its effects on depressive symptoms, anxiety and stress found that, while there may be a potential benefit to mood in people reporting high levels of stress, it was not beneficial for healthy people or those at risk of mood disorders. Researchers concluded that supplementation may benefit those who are at risk because of either poor nutrient status or stress. A large cross-sectional, population-based study using validated surveys to assess dietary intake of B vitamins and psychological health in Iranian adults found a beneficial effect from a higher intake of biotin and lower odds of anxiety, depression and stress, after adjusting for several confounding factors. An inverse relationship also was observed with vitamin B6 and the risk of stress. While the results were promising and suggested other B vitamins also may have an influence, researchers stated randomized, controlled trials are needed for further study.


Omega-3sOmega-3 fatty acids have been shown to upregulate neurogenesis, the process of new neuron development in adults, which can have a protective effect. An inverse relationship has been noted between eating more fish and lower risk of depression. Some studies have shown improvements in depressive symptoms with omega-3 fatty acid supplements, especially when used with antidepressant medications; other studies have found that any benefit may be small and not clinically significant. Natural Medicines database by TRC Healthcare lists eicosapentaenoic acid, or EPA, supplementation as possibly effective for those with MDD. However, it states that docosahexaenoic acid, or DHA, does not appear to improve any type of depression. In studies, 1 to 6 grams of omega-3 fatty acids EPA and DHA per day have been used, but the duration has varied from several weeks to months.


According to NHANES data and based on medical expenditures for antidepressant and antipsychotic medications, the use of medication for depression in the U.S. has been increasing. Antipsychotics and lithium are common treatments that have important dietary considerations.


Dietary Supplements and HerbalsIn February, the U.S. Food and Drug Administration warned of 10 companies illegally selling dietary supplements that claimed to treat depression and other mental health disorders. The warning states that any dietary supplements that claim to cure, treat, prevent or mitigate depression are considered unapproved new drugs and are potentially harmful.


Sleep, Stress Reduction and Physical ActivityWhile nutrition may play a role in the prevention and treatment of depression, some lifestyle factors also can make a difference. Some studies show a connection between sleep and depression, especially with insomnia. Depression disorders are associated with both reduced sleep duration and quality.


Role of RDNsNutrition and dietetics practitioners can play a vital role for patients or clients with depression, including MDD, but they need to have proper training and multidisciplinary support for the complex needs of people with these conditions. RDNs can use the Academy of Nutrition and Dietetics: Revised 2018 Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (Competent, Proficient, and Expert) in Mental Health and Addictions to build knowledge and expand their practice in these specialty areas.


Based on the results of the present study, an inverse association was found between intakes of MUFAs, oleic acid, ALA, and n-3:n-6 PUFAs ratio with odds of anxiety. In addition, higher intake of SFAs was associated with higher anxiety score. The study analysis showed that overall DFQ may be important in anxiety disorder. These results may help to develop nutritional interventions and dietary guidelines to prevent or reduce anxiety in women. Nevertheless, experimental studies are required to evaluate the effect of DFQ on anxiety disorder.


Mood and metabolic disorders are interrelated and may share common pathological processes. Autonomic neurons link the brain with the gastrointestinal tract and constitute a likely pathway for peripheral metabolic challenges to affect behaviors controlled by the brain. The activities of neurons along these pathways are regulated by glia, which exhibit phenotypic shifts in response to changes in their microenvironment. How glial changes might contribute to the behavioral effects of consuming a high-fat diet (HFD) is uncertain. Here, we tested the hypothesis that anxiogenic and depressive-like behaviors driven by consuming a HFD involve compromised duodenal barrier integrity and subsequent phenotypic changes to glia and neurons along the gut-brain axis.


Individuals with metabolic disorders such as obesity and type 2 diabetes (T2D) exhibit abnormal neuropsychological and behavioral functions, which may indicate shared pathological process [1]. Peripheral autonomic neural circuits monitor intestinal microbial and dietary contents and convey this information to the central nervous system (CNS) that, in turn, regulates behavior [2, 3]. The enteric nervous system (ENS) regulates moment-to-moment digestive functions and modulates metabolism through interactions with other autonomic neurons and central pathways [2]. Enteric neurons are altered by metabolic disorders and these changes include impaired inhibitory motor pathways in the duodenum that contributes to hyper-contractility and abnormal transmission between the gut and the brain [4]. The resulting effects lead to a failure in controlling glucose metabolism and contribute to insulin resistance [5].


Diabetics and individuals consuming a prolonged high-fat diet (HFD) develop low-grade inflammation in the small intestine that may compromise intestinal barrier function and alter the microenvironment within the ENS. Glial cell proliferation, nerve damage, and degeneration of inhibitory nitrergic neurons in the myenteric plexus have all been associated with intestinal dysmotility that occurs during the early stages of obesity [6]. Further prolongation of a HFD evokes depressive- and anxiety-like phenotypes associated with distinct alterations in the intestinal microbiome and brain metabolome that follow the disruption of intestinal barrier functions [7]. Based on this evidence, it is postulated that the increased translocation of microbes and their products across the impaired intestinal barrier negatively impacts the gut-brain circuits that control either energy metabolism or behaviors by establishing local neuroinflammation and enteric neuron dysfunction [6,7,8]. How neuropathological signaling triggered in the intestine reverberates through the nervous system is still unknown.


The goal of this study was to test whether consuming a HFD drives a temporal progression of changes in glia and neurons along the gut-brain axis. Further, we hypothesized that enteric glia contribute to neuropathological signals that travel to the CNS and produce anxiogenic and depressive-like behaviors. We addressed these questions by blocking glial functions with the gliotoxin fluorocitrate (FC) and studied the effects of a prolonged HFD across the gut-brain axis that extends from the duodenal myenteric plexuses to the brain areas involved in the control of mood. Collectively, our data identified glial-mediated signaling triggered in the duodenal enteric plexuses as a critical link between peripheral and central neurocircuits that could be harnessed by treatments focused on correcting metabolic diseases and related neurobehavioral disorders.


Schematic model of the gut-brain signaling during metabolic diseases and related behavioral disorders. Chronic exposure to high-fat diet (HFD) alters intestinal physiology, inducing a low-grade inflammation, dysbiosis, and increased mucosal permeability. Microbe-derived products that violate the impaired intestinal barrier may activate enteric glia within the enteric nervous system (ENS) via TLR4 pathway, leading to reactive gliosis and ENS neurons dysfunction. This elicits a glia-dependent signaling between the gastrointestinal tract and the brain responsible for impairing the energy metabolism and behavior, including depressive- and anxiety-like symptoms


Enteric glia regulate bi-directional interactions between the immune and nervous systems by releasing neurotrophic factors that modulate innate immune responses [27], contribute to the activation of muscularis macrophage [46], modulate adaptive immune responses to pathogenic microorganisms by taking part in the process of immune recognition of detrimental stimuli via MHCII [28] and TLR-2 and 4 [11, 28], and convey the vagal anti-inflammatory signals to resident immune cells during injury and inflammation. Here, we showed that enteric glia in duodenal myenteric plexus express GFAP and TLR4 in response to increased duodenal permeability induced by HFD after 6 and 20 weeks of the diet (Fig. 2). This supports previous studies showing that enteric glia respond to pathogenic bacteria by upregulating immunomodulatory mechanisms via the TLR4 pathway and orchestrate a persistent enteroglial-sustained inflammation in the human intestine through S100β/TLR4 axis [11, 28]. 2ff7e9595c


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