scholarly journals Metabolomic and Inflammatory Signatures of Symptom Dimensions in Major Depression

2021 ◽  
Author(s):  
Christopher R. Brydges ◽  
Sudeepa Bhattacharyya ◽  
Sia Mahmoudian Dehkordi ◽  
Yuri Milaneschi ◽  
Brenda Penninx ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Gut Microbiome ◽  
Serum Samples ◽  
Symptom Dimensions ◽  
Inflammatory Index ◽  
Markers Of Inflammation ◽  
Membrane Structure And Function ◽  
Long Chain

Background: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions. Methods: Using three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism. Results: The IMD clinical dimension and the inflammatory index were positively correlated (r=0.19, p=.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids. Conclusion: The IMD dimension of depression is reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.

1010-P: Effects of MEDI0382, an Oxyntomodulin-Like Peptide with Targeted GLP-1/Glucagon Receptor Activity, on Amino Acids, Ketones, and Free Fatty Acids

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1010-P
Author(s):  
VICTORIA E. PARKER ◽  
DARREN ROBERTSON ◽  
TAO WANG ◽  
DAVID C. HORNIGOLD ◽  
MAXIMILIAN G. POSCH ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Receptor Activity ◽  
Glucagon Receptor

scholarly journals Free Fatty Acids Interfere with the DNA Binding Activity of the Virulence Regulator PrfA of Listeria monocytogenes

2020 ◽  
Vol 202 (15) ◽  
Author(s):  
Patrícia T. dos Santos ◽  
Rikke S. S. Thomasen ◽  
Mathias S. Green ◽  
Nils J. Færgeman ◽  
Birgitte H. Kallipolitis
Keyword(s):  
Fatty Acids ◽  
Dna Binding ◽  
Free Fatty Acids ◽  
Antimicrobial Agents ◽  
Virulence Gene ◽  
Binding Activity ◽  
Content Type ◽  
Dna Binding Activity ◽  
Virulence Regulator ◽  
Long Chain

ABSTRACT Naturally occurring free fatty acids (FFAs) are recognized as potent antimicrobial agents that also affect the production of virulence factors in bacterial pathogens. In the foodborne pathogen Listeria monocytogenes, some medium- and long-chain FFAs act as antimicrobial agents as well as signaling compounds, causing a repression of transcription of virulence genes. We previously observed that the master virulence regulator PrfA is involved in both the antimicrobial and virulence-inhibitory response of L. monocytogenes to selected FFAs, but the underlying mechanisms are presently unknown. Here, we present a systematic analysis of the antimicrobial and PrfA-inhibitory activities of medium- and long-chain FFAs of various carbon chain lengths and degrees of saturation. We observed that exposure to specific antimicrobial and nonantimicrobial FFAs prevented PrfA-dependent activation of virulence gene transcription and reduced the levels of PrfA-regulated virulence factors. Thus, an antimicrobial activity was not compulsory for the PrfA-inhibitory ability of an FFA. In vitro binding experiments revealed that PrfA-inhibitory FFAs were also able to prevent the constitutively active variant PrfA* from binding to the PrfA box in the promoter region of the virulence gene hly, whereas noninhibitory FFAs did not affect its ability to bind DNA. Notably, the unsaturated FFAs inhibited the DNA binding activity of PrfA* most efficiently. Altogether, our findings support a model in which specific FFAs orchestrate a generalized reduction of the virulence potential of L. monocytogenes by directly targeting the key virulence regulator PrfA. IMPORTANCE Listeria monocytogenes is a Gram-positive pathogen able to cause foodborne infections in humans and animals. Key virulence genes in L. monocytogenes are activated by the transcription regulator PrfA, a DNA binding protein belonging to the CRP/FNR family. Various signals from the environment are known to affect the activity of PrfA, either positively or negatively. Recently, we found that specific medium- and long-chain free fatty acids act as antimicrobial agents as well as signaling compounds in L. monocytogenes. Here, we show that both antimicrobial and nonantimicrobial free fatty acids inhibit PrfA-dependent activation of virulence gene transcription by interfering with the DNA binding activity of PrfA. Our findings suggest that free fatty acids could be candidates for alternative therapies against L. monocytogenes.

scholarly journals Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
J. Thomas ◽  
C. J. Thomas ◽  
J. Radcliffe ◽  
C. Itsiopoulos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Neurodegenerative Disease ◽  
Dietary Intervention ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Early Prevention ◽  
Markers Of Inflammation ◽  
Long Chain

Alzheimer’s disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

Long-chain acyl CoA's and free fatty acids in rat brain after head injury

1997 ◽  
Vol 237 ◽  
pp. S25
Author(s):  
H. Heller ◽  
J. Deutsch ◽  
A.D. Purdon ◽  
S.I. Rapoport ◽  
M. Horowitz ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Head Injury ◽  
Free Fatty Acids ◽  
Rat Brain ◽  
Chain Acyl ◽  
Long Chain

A new pyrolytic process with potential to convert free fatty acids into long chain nitriles and H2 intermediated by Fe nitrate

2020 ◽  
Vol 145 ◽  
pp. 104726
Author(s):  
Fabiano Gomes Ferreira de Paula ◽  
Rafael César Gonçalves Pereira ◽  
Breno Frederico Pereira Paulo ◽  
José Domingos Ardisson ◽  
Zenilda de Lourdes Cardeal ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Long Chain
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