REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-κB activation

Lee, Dong-Keon; Kim, Taesam; Byeon, Junyoung; Park, Minsik; Kim, Suji; Kim, Joohwan; Choi, Seunghwan; Lee, Gihwan; Park, Chanin; Lee, Keun Woo; Kwon, Yong Jung; Lee, Jeong‐Hyung; Kwon, Young-Guen; Kim, Young-Myeong

doi:10.1038/s41467-022-34110-1

Cited by 14 publications

(29 citation statements)

References 73 publications

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“…Obesity has been reported to be associated with liver disease and progression of hepatic dysfunction and impaired liver function by a variety of mechanisms. 16 The HFD led to a fatty liver, which significantly decreased in RS consumption groups (Figure 1O). Enzyme activity, such as AST, ALT, and ALP, is the most commonly used indicator of liver disease, of which AST and ALT are traditionally considered markers of hepatocellular injury and ALP as a marker of cholestasis.…”

Section: ■ Results and Discussionmentioning

confidence: 91%

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Long-Term Consumption of Resistant Starch Induced Changes in Gut Microbiota, Metabolites, and Energy Homeostasis in a High-Fat Diet

Wang

Guo

et al. 2023

J. Agric. Food Chem.

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Considering that the study on the impact of the long-term consumption of resistant starch on metabolic syndromes induced by a high-fat diet (HFD) is rare, this investigation designed a 36-week consumption of HFD containing three RS levels (LRS, MRS, and HRS) for measuring changes in serum parameters, liver transcriptome, and gut microbiota. Results indicated that all levels of RS in HFD significantly reduced food intakes and body gain, followed by increased leptin and PYY, but did not show dose-dependence. Furthermore, MRS triggered a greater number of enriched pathways than the other RS groups, whereas no enriched pathway was noted in the HRS group. The Firmicutes/Bacteroidetes ratio can still predict changes in body weight for long-term observation, and isobutyrate was found to be positively related to Blautia. Importantly, a shifted ratio of Ruminococcaceae/Lactobacillaceae quickly occurred in the early stage of 12 weeks for all groups, but the ratio remained constant in HRS rather than in LRS and MRS, which might indicate both similarity and difference in the regulation of the metabolic syndromes among the three RS interventions.

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Section: ■ Results and Discussionmentioning

confidence: 91%

“…Obesity has been reported to be associated with liver disease and progression of hepatic dysfunction and impaired liver function by a variety of mechanisms . The HFD led to a fatty liver, which significantly decreased in RS consumption groups (Figure O).…”

Section: Resultsmentioning

confidence: 95%

Long-Term Consumption of Resistant Starch Induced Changes in Gut Microbiota, Metabolites, and Energy Homeostasis in a High-Fat Diet

Wang

Guo

et al. 2023

J. Agric. Food Chem.

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“…Based on our findings, pyruvate suppressed the TNFα induced nuclear translocation of p65. It was reported that NF-κB directly promotes adipogenesis [61], hence, the attenuation of p65 translocation and following NF-kB signaling also explains the inhibition of adipogenic differentiation of preadipocytes as well as the decreases in the expression of adipogenic genes, including PPARγ and CEBPα, in adipose SVF cells by pyruvate. This is also in agreement with a report showing that pharmacological restriction of the NF-κB pathway attenuated the differentiation of 3T3-L1 preadipocytes and human adipose stem cells into adipocytes in vitro [62].…”

Section: Discussionmentioning

confidence: 99%

Dietary Pyruvate Targets Cytosolic Phospholipase A2 to Mitigate Inflammation and Obesity in Mice

Hasan,

Ghani,

Zhao

et al. 2023

Preprint

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Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation, known as meta-inflammation. This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease. Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways. However, its role and molecular mechanism in obesity and associated complications are obscure. In this study, we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain, white adipose tissue inflammation, and metabolic dysregulation. To identify the target proteins of pyruvate, drug affinity responsive target stability was employed with proteomics, cellular thermal shift assay, and isothermal drug response to detect the interactions between pyruvate and its molecular targets. Consequently, we identified cytosolic phospholipase A2 (cPLA2 ) as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity, white adipose tissue inflammation, and hepatic steatosis in a cPLA2-dependent manner. Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated, confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity. Overall, our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity, but it also sheds light on the mechanism of its action. Pyruvate's prior clinical use indicates that it can be considered a safe and viable alternative for obesity, whether consumed as a dietary supplement or as part of a regular diet.

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“…The knockout of α4 leads to impaired adipogenesis as well as thermogenesis but increased insulin resistance. Lee et al [ 5 ] reported that regulated development and DNA damage response 1 (REDD1) upregulation can simulate preadipocyte differentiation through atypical IKK-independent NF-κB activation by sequestering IκBα from the NF-κB/IκBα complex. Adenosine monophosphate-activated protein kinase (AMPK) regulates energy balance and the metabolic switch.…”

Section: Introductionmentioning

confidence: 99%

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway

Chen

et al. 2023

Nutrients

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The leaf of Perilla frutescens (L.) Britt (PF) has been reported to negatively affect adipocyte formation, inhibit body-fat formation, and lower body weight. However, its effect on adipocyte browning remains unknown. Thus, the mechanism of PF in promoting adipocyte browning was investigated. The ingredients of PF were acquired from the online database and filtered with oral bioavailability and drug-likeness criteria. The browning-related target genes were obtained from the Gene Card database. A Venn diagram was employed to obtain the overlapped genes that may play a part in PF promoting adipocyte browning, and an enrichment was analysis conducted based on these overlapped genes. A total of 17 active ingredients of PF were filtered, which may regulate intracellular receptor-signaling pathways, the activation of protein kinase activity, and other pathways through 56 targets. In vitro validation showed that PF promotes mitochondrial biogenesis and upregulates brite adipocyte-related gene expression. The browning effect of PF can be mediated by the p38 MAPK pathway as well as PI3K-AKT pathway. The study revealed that PF could promote adipocyte browning through multitargets and multipathways. An in vitro study validated that the browning effect of PF can be mediated by both the P38 MAPK pathway and the PI3K-AKT pathway.

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REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-κB activation

Cited by 14 publications

References 73 publications

Long-Term Consumption of Resistant Starch Induced Changes in Gut Microbiota, Metabolites, and Energy Homeostasis in a High-Fat Diet

Long-Term Consumption of Resistant Starch Induced Changes in Gut Microbiota, Metabolites, and Energy Homeostasis in a High-Fat Diet

Dietary Pyruvate Targets Cytosolic Phospholipase A2 to Mitigate Inflammation and Obesity in Mice

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway

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