Inter-organ Communication in the Regulation of Lipid Metabolism: Focusing on the Network Between the Liver, Intestine, and Heart

Ito, Masanori; Adachi‐Akahane, Satomi

doi:10.1254/jphs.13r09cp

Cited by 34 publications

(22 citation statements)

References 35 publications

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“…S1) indicate Geh is thus far the only lipase that inhibits innate immune cell recognition of bacterial PAMPs and prevents their activation, we cannot yet rule out the possibility that Sal1 and SAUSA300_0641 contribute to the pathogenesis of S. aureus in unknown ways. The organs involved in lipid metabolism, such as the small intestine and liver, contain a greater diversity of lipids than organs like the heart and spleen (78,81,91,92). Therefore, from a nutrient acquisition standpoint, the lipid environment of other host tissues may require a range of lipolytic activities for an invading microbe to thrive.…”

Section: Discussionmentioning

confidence: 99%

Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses

Chen

Alonzo

2019

Proc. Natl. Acad. Sci. U.S.A.

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Commensal and pathogenic bacteria hydrolyze host lipid substrates with secreted lipases and phospholipases for nutrient acquisition, colonization, and infection. Bacterial lipase activity on mammalian lipids and phospholipids can promote release of free fatty acids from lipid stores, detoxify antimicrobial lipids, and facilitate membrane dissolution. The gram-positive bacterium Staphylococcus aureus secretes at least two lipases, Sal1 and glycerol ester hydrolase (Geh), with specificities for short- and long-chain fatty acids, respectively, each with roles in the hydrolysis of environmental lipids. In a recent study from our group, we made the unexpected observation that Geh released by S. aureus inhibits activation of innate immune cells. Herein, we investigated the possibility that S. aureus lipases interface with the host immune system to blunt innate immune recognition of the microbe. We found that the Geh lipase, but not other S. aureus lipases, prevents activation of innate cells in culture. Mutation of geh leads to enhancement of proinflammatory cytokine production during infection, increased innate immune activity, and improved clearance of the bacterium in infected tissue. These in vitro and in vivo effects on innate immunity were not due to direct functions of the lipase on mammalian cells, but rather a result of inactivation of S. aureus lipoproteins, a major pathogen-associated molecular pattern (PAMP) of extracellular gram-positive bacteria, via ester hydrolysis. Altogether, these studies provide insight into an adaptive trait that masks microbial recognition by innate immune cells through targeted inactivation of a broadly conserved PAMP.

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Section: Discussionmentioning

confidence: 99%

Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses

Chen

Alonzo

2019

Proc. Natl. Acad. Sci. U.S.A.

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“…PPAR-a is highly expressed in liver, where it regulates multiple genes encoding for enzymes involved in fatty acid b-oxidation (20,21). CPT-1 is located in the mitochondrial membrane, which can promote the transport of long-chain fatty acids into the mitochondria to further participate in the b-oxidation process and becomes a rate-limiting enzyme for fatty acid oxidation.…”

Section: Discussionmentioning

confidence: 99%

Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats

Chen

et al. 2015

Journal of Pharmacological Sciences

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Oleoylethanolamine (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor alpha (PPAR-α), has revealed the pharmacological properties in the treatment of obesity, atherosclerosis and other diseases through the modulation of lipid metabolism. To assess whether OEA can also regulate non-alcoholic fatty liver disease (NAFLD) caused by fat accumulation, we administrated OEA or fenofibrate in Sprague Dawley (SD) rats fed with a high fat diet (HFD). After 6 or 17 weeks treatment, OEA (5 mg/kg/day, i.p.) relieved the development of NAFLD compared with control groups by regulating the levels of plasma TG, TC, ALT and AST and liver inflammatory cytokines. Gene expression analysis of liver tissue and plasma from the animal models showed that OEA and fenofibrate both promoted the lipid β-oxidation by activating PPAR-α. Detailed research revealed that OEA inhibited the mRNA expression of lipogenesis in a PPAR-α-independant manner, while fenofibrate expressed an opposite effection. In summary, our research results suggested that as a potential lead compound, OEA could improve HFD-induced NAFLD with higher efficacy and safety than fenofibrate.

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“…The dynamic liquid-liquid immiscibility and membrane bioactivity is created by sphingolipid-cholesterol selfassembly with proteins in lipid rafts [63]. Decoration of proteins with glycosylphosphatidylinositols are critical for their trafficking to lipid rafts and the outer leaflet of the plasma membrane [64]. Perturbation of membrane microstructures by HDL may explain the observed antiinflammatory effects in innate immune cells.…”

Section: Lipid-protein Interactionsmentioning

confidence: 99%

Lipidomics in Health and Diseases - Beyond the Analysis of Lipids

Fan¹

2015

J Glycomics Lipidomics

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The role of lipids in human health and disease is taking the center stage. In the last decades, there has been an intense effort to develop suitable methodologies to discover, identify, and quantitatively monitor lipids in biological systems. Recent advancement of mass spectrometry technology has provided a variety of tools for global study of the lipid "Omes", including the quantification of known lipid molecular species and the identification of novel lipids that possess pathophysiological functions. Lipidomics has thus emerged as a discipline for comprehensively illuminating lipids, lipidderived mediators and lipid networks in body fluids, tissues and cells. However, owing to the complexity and diversity of the lipidome, lipid research is challenging. Here, the experimental strategies for lipid isolation and characterization will be presented, especially for those who are new to the field of lipid research. Because lipids are known to participate in a host of protein signaling and trafficking pathways, the review emphasizes the understanding of interactions between cellular components, in particular the lipid-protein interrelationships. Novel tools for probing lipid-protein interactions by advanced mass spectrometric techniques will be discussed. It is expected that by integrating the approaches of lipidomics, transcriptomics and proteomics, a clear understanding of the complex functions of lipids will eventually be translated into human diseases.

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Inter-organ Communication in the Regulation of Lipid Metabolism: Focusing on the Network Between the Liver, Intestine, and Heart

Cited by 34 publications

References 35 publications

Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses

Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses

Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats

Lipidomics in Health and Diseases - Beyond the Analysis of Lipids

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