Involvement of de novo ceramide synthesis in pro-inflammatory adipokine secretion and adipocyte–macrophage interaction

Hamada, Yoji; Nagasaki, Hiroshi; Fujiya, Atsushi; Seino, Yusuke; Shang, Qing Long; Suzuki, Takeshi; Hashimoto, Hiroyuki; Oiso, Yutaka

doi:10.1016/j.jnutbio.2014.07.008

Cited by 28 publications

(20 citation statements)

References 40 publications

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“…Several palmitate concentrations and times of incubation were used to better fit the different dose and time responses of the cytokines and parameters measured. Consistent with previous studies (9,11), palmitate incubation raised cytokines expression two-to threefold.…”

Section: Enhanced Adipocyte Fao Improves Insulin Sensitivity and Redusupporting

confidence: 92%

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Malandrino

Fucho

Weber

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

155

110

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-Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CAR⌬1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.

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Section: Enhanced Adipocyte Fao Improves Insulin Sensitivity and Redusupporting

confidence: 92%

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Malandrino

Fucho

Weber

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

155

110

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“…Some evidence suggests that ceramides increase both adipokine expression and its level in the circulation . Available data indicate a strong link between ceramides and adipokines . Hamada et al .…”

Section: Ceramides and Insulin Resistancementioning

confidence: 99%

“…Some evidence suggests that ceramides increase both adipokine expression and its level in the circulation [48]. Available data indicate a strong link between ceramides and adipokines [48,76]. Hamada et al [76] showed that ceramides stimulate pro-inflammatory adipokine secretion as well as IL-6 and monocyte chemo-attractant protein-1 in mature 3T3-L1 adipocytes.…”

Section: Ceramide and Adipokines Expression/releasementioning

confidence: 99%

Ceramides and diabetes mellitus: an update on the potential molecular relationships

Yaribeygi

Ruscica

et al. 2019

Diabet. Med.

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Recent evidence suggests that ceramides can play an important pathophysiological role in the development of diabetes. Ceramides are primarily recognized as lipid bilayer building blocks, but recent work has shown that these endogenous molecules are important intracellular signalling mediators and may exert some diabetogenic effects via molecular pathways involved in insulin resistance, β‐cell apoptosis and inflammation. In the present review, we consider the available evidence on the possible roles of ceramides in diabetes mellitus and introduce eight different molecular mechanisms mediating the diabetogenic action of ceramides, categorized into those predominantly related to insulin resistance vs those mainly implicated in β‐cell dysfunction. Specifically, the mechanistic evidence involves β‐cell apoptosis, pancreatic inflammation, mitochondrial stress, endoplasmic reticulum stress, adipokine release, insulin receptor substrate 1 phosphorylation, oxidative stress and insulin synthesis. Collectively, the evidence suggests that therapeutic agents aimed at reducing ceramide synthesis and lowering circulating levels may be beneficial in the prevention and/or treatment of diabetes and its related complications.

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“…Moreover, signaling lipids, such as ceramides, are implicated in pathways regulating inflammation [21, 22]. As polyphenols have been shown to exert pronounced effects on hepatic lipid metabolism, particularly under pathological conditions [23], we further aimed to find out whether feeding of GSGME could influence metabolism of glycerophospholipids and ceramides.…”

Section: Introductionmentioning

confidence: 99%

Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract

Geßner

Winkler²,

Koch

et al. 2017

BMC Genomics

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BackgroundIt was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract (GSGME) during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum.ResultsTranscriptomic analysis of the liver revealed 207 differentially expressed transcripts, from which 156 were up- and 51 were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation and the most enriched Kyoto Encyclopedia of Genes and Genomes pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that a great part of these genes are involved in endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and inflammatory processes. Accordingly, protein folding, response to unfolded protein, unfolded protein binding, chemokine activity and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins serum amyloid A (SAA) and haptoglobin were reduced in cows fed GSGME compared to control cows. Lipidomic analysis of plasma revealed no differences in the concentrations of individual species of major and minor lipid classes between cows fed GSGME and control cows.ConclusionsAnalysis of hepatic transcript profile in cows fed GSGME during the transition period at 1 week postpartum indicates that polyphenol-rich feed components are able to inhibit ER stress-induced UPR and inflammatory processes, both of which are considered to contribute to liver-associated diseases and to impair milk performance in dairy cows, in the liver of dairy cows during early lactation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3638-1) contains supplementary material, which is available to authorized users.

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Involvement of de novo ceramide synthesis in pro-inflammatory adipokine secretion and adipocyte–macrophage interaction

Cited by 28 publications

References 40 publications

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Ceramides and diabetes mellitus: an update on the potential molecular relationships

Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract

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