Photoactivation of Dok1/ERK/PPARγ signaling axis inhibits excessive lipolysis in insulin-resistant adipocytes

Jiang, Xiaoxiao; Huang, Lei; Xing, Da

doi:10.1016/j.cellsig.2015.03.010

Cited by 19 publications

(13 citation statements)

References 45 publications

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“…PPAR plays an important role in adipogenesis, adipocyte gene expression, and fat cell differentiation, which promote lipid storage and metabolism [40, 41]. Moreover, the PPAR signaling axis is also a potential target for the modulation of adipogenesis [42]. Interestingly, our whole microbial genome sequencing results suggested that, compared to the lean line, the PPAR signal pathway of gut microbiota in the fat line had a significantly higher functional performance (Fig.…”

Section: Discussionmentioning

confidence: 99%

Divergent selection-induced obesity alters the composition and functional pathways of chicken gut microbiota

et al. 2016

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BackgroundThe gastrointestinal tract is populated by a complex and vast microbial network, with a composition that reflects the relationships of the symbiosis, co-metabolism, and co-evolution of these microorganisms with their host. The mechanism that underlies such interactions between the genetics of the host and gut microbiota remains elusive.ResultsTo understand how genetic variation of the host shapes the gut microbiota and interacts with it to affect the metabolic phenotype of the host, we compared the abundance of microbial taxa and their functional performance between two lines of chickens (fat and lean) that had undergone long-term divergent selection for abdominal fat pad weight, which resulted in a 4.5-fold increase in the fat line compared to the lean line. Our analysis revealed that the proportions of Fusobacteria and Proteobacteria differed significantly between the two lines (8 vs. 18% and 33 vs. 24%, respectively) at the phylum level. Eight bacterial genera and 11 species were also substantially influenced by the host genotype. Differences between the two lines in the frequency of host alleles at loci that influence accumulation of abdominal fat were associated with differences in the abundance and composition of the gut microbiota. Moreover, microbial genome functional analysis showed that the gut microbiota was involved in pathways that are associated with fat metabolism such as lipid and glycan biosynthesis, as well as amino acid and energy metabolism. Interestingly, citrate cycle and peroxisome proliferator activated receptor (PPAR) signaling pathways that play important roles in lipid storage and metabolism were more prevalent in the fat line than in the lean line.ConclusionsOur study demonstrates that long-term divergent selection not only alters the composition of the gut microbiota, but also influences its functional performance by enriching its relative abundance in microbial taxa. These results support the hypothesis that the host and gut microbiota interact at the genetic level and that these interactions result in their co-evolution.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0270-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Divergent selection-induced obesity alters the composition and functional pathways of chicken gut microbiota

et al. 2016

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“…The sequences of primers for PCR amplification were as follows: GAPDH: forward, 5′-AGGTCGGTGTGAACGGATTTG-3′; reverse, 5′-TGTAGACCATGTAGTTGAGGTCA-3′ [21]; PPAR- γ : forward, 5′-TTTTCAAGGGTGCCAGTTTC-3′; reverse, 5′-TCTGTGACGATCTGCCTGAG-3′; FABP4: forward, 5′-TCCAGTGAAAACTTTGATGATTAT-3′; reverse, 5′-ACGCATTCCACCACCAGTTTATCA-3′ [22]. Quantitative PCR analysis was performed using SYBR Select Master Mix in 7500 Fast Real-Time PCR System.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Feng

Zhang

et al. 2016

Mediators of Inflammation

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High mobility group box 1 protein (HMGB1) is a molecule related to the development of inflammation. Autophagy is vital to maintain cellular homeostasis and protect against inflammation of adipocyte injury. Our recent work focused on the relationship of HMGB1 and autophagy in 3T3-L1 cells. In vivo experimental results showed that, compared with the normal-diet group, the high-fat diet mice displayed an increase in adipocyte size in the epididymal adipose tissues. The expression levels of HMGB1 and LC3II also increased in epididymal adipose tissues in high-fat diet group compared to the normal-diet mice. The in vitro results indicated that HMGB1 protein treatment increased LC3II formation in 3T3-L1 preadipocytes in contrast to that in the control group. Furthermore, LC3II formation was inhibited through HMGB1 knockdown by siRNA. Treatment with the HMGB1 protein enhanced LC3II expression after 2 and 4 days but decreased the expression after 8 and 10 days among various differentiation stages of adipocytes. By contrast, FABP4 expression decreased on the fourth day and increased on the eighth day. Hence, the HMGB1 protein modulated autophagy-related proteins and lipid-metabolism-related genes in adipocytes and could be a new target for treatment of obesity and related metabolic diseases.

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“…We and others collected evidence for a feed-forward amplification loop (see model in S16), where PPARγ induces DOK1, and DOK1 in turn increases the transcriptional activity of PPARγ via its dual function as a transcription factor cochaperone and RAS-MEK1/2-ERK1/2 pathway inhibitor relieving inhibitory post-translational modifications from PPARγ. 8,12,63,64 In this context, PPARγ-agonist may be used as pharmacological tool to boost this reshaping of macrophage phenotypes and effector profiles. 25 The results obtained from this study suggest a novel role for DOK1 in patients with EBV+ gastric cancer, where it was found to be co-upregulated with toll-like receptors and targets of clinical immunotherapy (e.g., PD1, PD-L1, CTLA4).…”

Section: Discussionmentioning

confidence: 99%

Docking protein-1 promotes inflammatory macrophage signaling in gastric cancer

Sara

et al. 2019

OncoImmunology

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Docking protein-1 (DOK1) is a tumor suppressor frequently lost in malignant cells, however, it retains the ability to control activities of immune receptors in adjacent stroma cells of the tumor microenvironment. We therefore hypothesized that addressing DOK1 may be useful for cancer immunotherapy. DOK1 mRNA and DOK1 protein expression were downregulated in tumor cells of gastric cancer patients (n = 249). Conversely, its expression was up-regulated in cases positive for Epstein Barr Virus (EBV+) together with genes related to macrophage biology and targets of clinical immunotherapy such as programmed-cell-death-ligand-1 (PD-L1). Notably, high DOK1 positivity in stroma cells conferred poor prognosis in patients and correlated with high levels of inducible nitric oxide synthase in CD68+ tumor-associated macrophages. In macrophages derived from human monocytic leukemia cell lines, DOK1 (i) was inducible by agonists of the anti-diabetic transcription factor peroxisome proliferator-activated receptor-gamma (PPARγ), (ii) increased polarization towards an inflammatory phenotype, (iii) augmented nuclear factor-κB-dependent transcription of pro-inflammatory cytokines and (iv) reduced PD-L1 expression. These properties empowered DOK1+ macrophages to decrease the viability of human gastric cancer cells in contact-dependent co-cultures. DOK1 also reduced PD-L1 expression in human primary blood monocytes. Our data propose that the drugability of DOK1 may be exploited to reprogram myeloid cells and enforce the innate immune response against EBV+ human gastric cancer.

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Photoactivation of Dok1/ERK/PPARγ signaling axis inhibits excessive lipolysis in insulin-resistant adipocytes

Cited by 19 publications

References 45 publications

Divergent selection-induced obesity alters the composition and functional pathways of chicken gut microbiota

Divergent selection-induced obesity alters the composition and functional pathways of chicken gut microbiota

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Docking protein-1 promotes inflammatory macrophage signaling in gastric cancer

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