Free fatty acid receptors as therapeutic targets for the treatment of diabetes

Ichimura, Atsuhiko; Hasegawa, Sae; Kasubuchi, Mayu; Kimura, Ikuo

doi:10.3389/fphar.2014.00236

Cited by 155 publications

(113 citation statements)

References 40 publications

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“…FAs induce connexin (Cx) responses by interacting with membrane receptors, such as members of the G-protein coupled receptors (GPCRs), for example, GPR40 (free fatty acid receptor 1, FFAR1) or GPR120 (FFAR4), which are activated by medium- and long-chain FAs (Ichimura et al, 2014). The activation of these FFARs could involve an intracellular signaling pathway associated with different protein kinases (e.g., PKC, MAPK or AKT).…”

Section: Resultsmentioning

confidence: 99%

Regulation of Connexin-Based Channels by Fatty Acids

et al. 2017

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In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood.

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Section: Resultsmentioning

confidence: 99%

Regulation of Connexin-Based Channels by Fatty Acids

et al. 2017

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“…The recent research highlighted the prominent role of SCFAs produced by Lactobacillus species in energy homeostasis and they serve as magnificent ligands for two orphan GPCRs receptors, GPR41 (known as FFAR3) and GPR43 (known as FFAR2) [128]. Acetate and propionate binds to the FFAR2 whereas FFAR3 has been more often activated by propionate and butyrate [129].…”

Section: Role In Diabetes and Obesitymentioning

confidence: 99%

Metabiotics: The Functional Metabolic Signatures of Probiotics: Current State-of-Art and Future Research Priorities—Metabiotics: Probiotics Effector Molecules

Singh¹,

Vishwakarma²,

Singhal³

2018

ABB

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The intricate "orchestered molecular conversation" between the host and gut microbiome is one of the most dynamic research areas in recent years. The rhythmic chemical cross talk in the form of bioactive metabolites and signalling molecules synthesized by gut microbiome plays a significant role for the modulation of human health in diversified ways. They are recognized as low molecular weight (LMW) molecules having versatile chemical attributes. They possess magnificent capability of interacting with surrounding environment and controlling the genes for various genetic, biochemical and physiological functions for maintaining the homeostasis that is now-a-days termed as "small molecules microbes originated (SMOM) homeostasis" in the host. These metabolic signatures have close structural and functional resemblance with small molecules synthesized by host eukaryotic cells and dietary components. Therefore, they may be considered as universalized metabolites contributing to the remarkable phenomenon of epigenetic regulation, cell to cell communication and stability of genome manifesting the overall growth and development of the host and known as "metabiotics". The wide panorama of utilization of probiotics is continuously expanding and conferring the major health benefits through metabiotic components are gaining tremendous momentum therefore recognized as "hidden soldiers" of the body. Therefore firstly, we outline the need and types of metabiotic molecules and depicting their role in human health. Then, we summarize their preventive and therapeutic avenues in various diseases and finally, we propose the current technological interventions, bottlenecks and future perspectives in this field that are implied for accelerating their comprehensive understanding and utilization at industrial scale.

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“…SCFAs are ligands for the G-protein coupled receptors GPR43 and GPR41. 27) These receptors are widely expressed and play roles in the regulation of energy metabolism, the sympathetic nerve system, and immune cell function. Taken together, these differences in gut bacteria may be related to the amount of SCFAs produced and affect the incidence of several diseases.…”

Section: Gut Microbiota and Their Metabolites: Bile Acids And Short Cmentioning

confidence: 99%

Gut Microbiota and Coronary Artery Disease

et al. 2016

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SummaryGut microbiota have been attracting increased attention in many fields of medicine recently. We can perform a comprehensive analysis of gut microbiota using next-generation sequencing techniques together with bioinformatics technology, which expands our knowledge of a large ecosystem consisting of a host and gut microbiota. We summarize some reports about the correlations between gut microbiota and metabolic disorders, particularly atherosclerosis, and discuss future directions for the diagnostic or therapeutic potential of gut microbiota. To take simple examples, we demonstrated that the order Lactobacillales was significantly increased; while the phylum Bacteroidetes was significantly decreased in coronary artery disease (CAD) patients compared with controls or healthy volunteers. The characteristics of gut microbiota in type 2 diabetes and dyslipidemia have been reported. However, these studies have limitations, and the biological significance of gut microbiota and the causal relationships are still controversial. We hope the reports listed in this review article might lead to the development of a novel therapy to prevent CAD via modulating gut microbiota or their metabolites. (Int Heart J 2016; 57: 663-671)

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Free fatty acid receptors as therapeutic targets for the treatment of diabetes

Cited by 155 publications

References 40 publications

Regulation of Connexin-Based Channels by Fatty Acids

Regulation of Connexin-Based Channels by Fatty Acids

Metabiotics: The Functional Metabolic Signatures of Probiotics: Current State-of-Art and Future Research Priorities—Metabiotics: Probiotics Effector Molecules

Gut Microbiota and Coronary Artery Disease

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