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Long Chain n-3 Fatty Acids Improve Depression Syndrome in Type 2 Diabetes Mellitus.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is commonly associated with depressive symptoms, which affect prognosis and quality of life. We investigated the antidepressant effects of n-3 fatty acids (n-3FAs) monotherapy (without conventional antidepressants) for T2DM patients with mild to moderate depressive symptoms.A 10-wk, placebo-controlled, double-blind, parallel-group (1:1 ratio) randomized trial of n-3FAs (2700 mg/day EPA: DHA ratio=2) versus placebo in 88 Iranian diabetic patients with mild to moderate depression based on Beck Depression Inventory II (BDI-II-PERSIAN) was conducted. This study started from July 2014 to January 2015 in Tehran University of Medical Sciences, Tehran, Iran. The primary event was defined as worsened, non-changed, or inconsiderably improved depression (<5 unit decrease in BDI-II-PERSIAN depression scores after treatment) (ClinicalTrials.gov Identifier: NCT02261545).Randomly, 44 T2DM patients were treated with n-3FAs supplements and 44 cases received placebo (three patients discontinued). n-3FAs could significantly protect patients against the aforesaid event and exhibit satisfactory prevention (number needed to treat with 95% confidence interval: 2.52, 1.71-4.74). No serious adverse reactions were reported.n-3FAs supplementation had significant antidepressant effects in T2DM patients with mild to moderate depressive symptoms, not confounded by metabolic factors and disease duration.

SUBMITTER: Mazaherioun M

PROVIDER: S-EPMC5996325 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Long Chain n-3 Fatty Acids Improve Depression Syndrome in Type 2 Diabetes Mellitus.

Mazaherioun Maryam M Saedisomeolia Ahmad A Javanbakht Mohammad Hassan MH Koohdani Fariba F Zarei Mahnaz M Ansari Samaneh S Khoshkhoo Bazargani Fatemeh F Djalali Mahmoud M

Iranian journal of public health 20180401 4

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is commonly associated with depressive symptoms, which affect prognosis and quality of life. We investigated the antidepressant effects of n-3 fatty acids (n-3FAs) monotherapy (without conventional antidepressants) for T2DM patients with mild to moderate depressive symptoms.<h4>Methods</h4>A 10-wk, placebo-controlled, double-blind, parallel-group (1:1 ratio) randomized trial of n-3FAs (2700 mg/day EPA: DHA ratio=2) versus placebo in 88 Iranian d ...[more]

PMID: 29900143

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Project description:Concerns about global warming, fossil-fuel depletion, food security, and human health have promoted metabolic engineers to develop tools/strategies to overproduce microbial functional oils directly from renewable resources. Medium-chain fatty acids (MCFAs, C8-C12) have been shown to be important sources due to their diverse biotechnological importance, providing benefits ranging from functional lipids to uses in bio-fuel production. However, oleaginous microbes do not carry native pathways for the production of MCFAs, and therefore, diverse approaches have been adapted to compensate for the requirements of industrial demand. Mucor circinelloides is a promising organism for lipid production (15-36% cell dry weight; CDW) and the investigation of mechanisms of lipid accumulation; however, it mostly produces long-chain fatty acids (LCFAs). To address this challenge, we genetically modified strain M. circinelloides MU758, first by integrating heterologous acyl-ACP thioesterase (TE) into fatty acid synthase (FAS) complex and subsequently by modifying the ?-oxidation pathway by disrupting the acyl-CoA oxidase (ACOX) and/or acyl-CoA thioesterase (ACOT) genes with a preference for medium-chain acyl-CoAs, to elevate the yield of MCFAs. The resultant mutant strains (M-1, M-2, and M-3, respectively) showed a significant increase in lipid production in comparison to the wild-type strain (WT). MCFAs in M-1 (47.45%) was sharply increased compared to the wild type strain (2.25%), and it was further increased in M-2 (60.09%) suggesting a negative role of ACOX in MCFAs production. However, MCFAs in M-3 were much decreased compared to M-1,suggesting a positive role of ACOT in MCFAs production. The M-2 strain showed maximum lipid productivity (~1800 milligram per liter per day or mg/L.d) and MCFAs productivity (~1100 mg/L.d). Taken together, this study elaborates on how the combination of two multidimensional approaches, TE gene over-expression and modification of the ?-oxidation pathway via substantial knockout of specific ACOX gene, significantly increased the production of MCFAs. This synergistic approach ultimately offers a novel opportunity for synthetic/industrial biologists to increase the content of MCFAs.

Project description:Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut-brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut-brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed that SCFAs induced altered contralesional cortex connectivity. This was associated with SCFA-dependent changes in spine and synapse densities. RNA sequencing of the forebrain cortex indicated a potential involvement of microglial cells in contributing to the structural and functional remodeling. Further analyses confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFAs modulate poststroke recovery via effects on systemic and brain resident immune cells.SIGNIFICANCE STATEMENT Previous studies have shown a bidirectional communication along the gut-brain axis after stroke. Stroke alters the gut microbiota composition, and in turn, microbiota dysbiosis has a substantial impact on stroke outcome by modulating the immune response. However, until now, the mediators derived from the gut microbiome affecting the gut-immune-brain axis and the molecular mechanisms involved in this process were unknown. Here, we demonstrate that short-chain fatty acids, fermentation products of the gut microbiome, are potent and proregenerative modulators of poststroke neuronal plasticity at various structural levels. We identified that this effect was mediated via circulating lymphocytes on microglial activation. These results identify short-chain fatty acids as a missing link along the gut-brain axis and as a potential therapeutic to improve recovery after stroke.

Dataset Information

Long Chain n-3 Fatty Acids Improve Depression Syndrome in Type 2 Diabetes Mellitus.

Publications

Long Chain n-3 Fatty Acids Improve Depression Syndrome in Type 2 Diabetes Mellitus.

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