FFAR2/3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View

Mishra, Sidharth Prasad; Karunakar, Prashantha; Taraphder, Subhash; Yadav, Hariom

doi:10.20944/preprints202005.0037.v1

Cited by 19 publications

(1 citation statement)

References 127 publications

(316 reference statements)

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“…Both mouse and human adipose tissue abundantly express FFAR2 [25,26]. On the other hand FFAR3 is expressed in pancreatic β cells, immune cells, central nervous system and enteroendocrine cells [8,[27][28][29]. However, FFAR3 is not expressed in human or mouse adipose tissue or in adipocytes.…”

Section: Ffar2 and Ffar4 Are Highly Expressed In Adipose Tissuementioning

confidence: 99%

Free Fatty Acid Receptors (FFARs) In Adipose: Physiological Role and Therapeutic Outlook

Mahri¹,

Malik²,

Ibrahim³

et al. 2021

Preprint

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Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.

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Section: Ffar2 and Ffar4 Are Highly Expressed In Adipose Tissuementioning

confidence: 99%

Free Fatty Acid Receptors (FFARs) In Adipose: Physiological Role and Therapeutic Outlook

Mahri¹,

Malik²,

Ibrahim³

et al. 2021

Preprint

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Evolutionary concepts in the functional biotics arena: a mini-review

Nataraj

Shivanna

Rao

et al. 2020

Food Sci Biotechnol

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Over the years, the attempts to elucidate the role of beneficial microorganisms in shaping human health are becoming fairly apparent. The functional impact conferred by such microbes is not only transmitted by viable cells or their metabolites but also through non-viable cells. Extensive research to unveil the protective action of such wonder bugs has resulted in categorizing the beneficial microflora and their bioactive metabolites into a variety of functional biotic concepts based on their intended applications in various forms. In the modern era, these are often termed as probiotics, prebiotics, synbiotics, postbiotics, next-generation probiotics, psychobiotics, oncobiotics, pharmabiotics, and metabiotics. Currently, the concept of traditional probiotics is being widened to include microbes beyond lactic acid bacteria. Indeed, this diversification has broadened the functional food portfolio from food to pharmaceuticals. In this context, the present review aims to summarize the existing biotic concepts and their differences thereof.

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Parkinson’s Disease and the Metal–Microbiome–Gut–Brain Axis: A Systems Toxicology Approach

et al. 2021

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Parkinson’s Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventually affecting the central nervous system. The correlation between dysbiosis and PD suggests a functional and bidirectional communication between the gut and the brain. The bioaccumulation of metals promotes stress mechanisms by increasing reactive oxygen species, likely altering the bidirectional gut–brain link. To better understand the differing molecular mechanisms underlying PD, integrative modeling approaches are necessary to connect multifactorial perturbations in this heterogeneous disorder. By exploring the effects of gut microbiota modulation on dietary heavy metal exposure in relation to PD onset, the modification of the host-associated microbiome to mitigate neurological stress may be a future treatment option against neurodegeneration through bioremediation. The progressive movement towards a systems toxicology framework for precision medicine can uncover molecular mechanisms underlying PD onset such as metal regulation and microbial community interactions by developing predictive models to better understand PD etiology to identify options for novel treatments and beyond. Several methodologies recently addressed the complexity of this interaction from different perspectives; however, to date, a comprehensive review of these approaches is still lacking. Therefore, our main aim through this manuscript is to fill this gap in the scientific literature by reviewing recently published papers to address the surrounding questions regarding the underlying molecular mechanisms between metals, microbiota, and the gut–brain-axis, as well as the regulation of this system to prevent neurodegeneration.

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FFAR2/3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View

Cited by 19 publications

References 127 publications

Free Fatty Acid Receptors (FFARs) In Adipose: Physiological Role and Therapeutic Outlook

Free Fatty Acid Receptors (FFARs) In Adipose: Physiological Role and Therapeutic Outlook

Evolutionary concepts in the functional biotics arena: a mini-review

Parkinson’s Disease and the Metal–Microbiome–Gut–Brain Axis: A Systems Toxicology Approach

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