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Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation.

ABSTRACT: Adipogenic differentiation is a highly regulated process that is necessary for metabolic homeostasis and nutrient sensing. The expression of PPAR? and the subsequent activation of adipogenic genes is critical for the process. In this study, we identified lanthionine synthetase C-like protein 2 (LanCL2) as a positive regulator of adipogenesis in 3T3-L1 cells. Knockdown of LanCL2, but not LanCL1, inhibited adipogenic differentiation, and this effect was not mediated through cAMP or Akt signaling pathways. The expression of early adipogenic markers CCAAT enhancer binding protein ? (C/EBP?) and C/EBP? remained intact in LanCL2 knockdown cells, but levels of late adipogenic markers PPAR? and C/EBP? were suppressed. The addition of the naturally occurring PPAR? activator 15-deoxy-?^12,14-prostaglandin J2 or conditioned medium from differentiating cells did not restore differentiation, implying that LanCL2 may not be involved in the production of a secreted endogenous PPAR? ligand. Pulldown assays demonstrated a direct physical interaction between LanCL2 and PPAR?. Consistent with a regulatory role of LanCL2, luciferase reporter assays revealed that full transcriptional activation by PPAR? was dependent on LanCL2. Taken together, our study reveals a novel role of LanCL2 in adipogenesis, specifically involved in PPAR?-mediated transactivation of downstream adipogenic genes.

SUBMITTER: Dutta D

PROVIDER: S-EPMC6071776 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation.

Dutta Debapriya D Lai Kuan-Yu KY Reyes-Ordoñez Adriana A Chen Jie J van der Donk Wilfred A WA

Journal of lipid research 20180607 8

Adipogenic differentiation is a highly regulated process that is necessary for metabolic homeostasis and nutrient sensing. The expression of PPARγ and the subsequent activation of adipogenic genes is critical for the process. In this study, we identified lanthionine synthetase C-like protein 2 (LanCL2) as a positive regulator of adipogenesis in 3T3-L1 cells. Knockdown of LanCL2, but not LanCL1, inhibited adipogenic differentiation, and this effect was not mediated through cAMP or Akt signaling p ...[more]

PMID: 29880530

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Project description:Immune responses to Helicobacter pylori are orchestrated through complex balances of host-bacterial interactions, including inflammatory and regulatory immune responses across scales that can lead to the development of the gastric disease or the promotion of beneficial systemic effects. While inflammation in response to the bacterium has been reasonably characterized, the regulatory pathways that contribute to preventing inflammatory events during H. pylori infection are incompletely understood. To aid in this effort, we have generated a computational model incorporating recent developments in the understanding of H. pylori-host interactions. Sensitivity analysis of this model reveals that a regulatory macrophage population is critical in maintaining high H. pylori colonization without the generation of an inflammatory response. To address how this myeloid cell subset arises, we developed a second model describing an intracellular signaling network for the differentiation of macrophages. Modeling studies predicted that LANCL2 is a central regulator of inflammatory and effector pathways and its activation promotes regulatory responses characterized by IL-10 production while suppressing effector responses. The predicted impairment of regulatory macrophage differentiation by the loss of LANCL2 was simulated based on multiscale linkages between the tissue-level gastric mucosa and the intracellular models. The simulated deletion of LANCL2 resulted in a greater clearance of H. pylori, but also greater IFN? responses and damage to the epithelium. The model predictions were validated within a mouse model of H. pylori colonization in wild-type (WT), LANCL2 whole body KO and myeloid-specific LANCL2-/- (LANCL2Myeloid) mice, which displayed similar decreases in H. pylori burden, CX3CR1+ IL-10-producing macrophages, and type 1 regulatory (Tr1) T cells. This study shows the importance of LANCL2 in the induction of regulatory responses in macrophages and T cells during H. pylori infection.

Dataset Information

Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation.

Publications

Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation.

Similar Datasets

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