NF-κB p65 regulates hepatic lipogenesis by promoting nuclear entry of ChREBP in response to a high carbohydrate diet

Daniel, P. Vineeth; Dogra, Surbhi; Rawat, Priya; Choubey, Abhinav; Khan, Aiysha Siddiq; Rajak, Sangam; Kamthan, Mohan; Mondal, Prosenjit

doi:10.1016/j.jbc.2021.100714

Cited by 22 publications

(16 citation statements)

References 54 publications

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“…On the other hand, olfactomedin 4 (OLFM4) belongs to OLFM group V. This glycoprotein was found to be endogenously expressed in bone marrow and the small intestine, stomach, colon, prostate [21] and pancreas [22]. In addition, this protein has been related to multiple signalling pathways and factors, including the NF-κB [23] WNT/β-catenin pathway [24,25] and Notch proteins [26,27], which are strongly related to pathological processes in hepatic diseases, such as NAFLD [28][29][30]. Furthermore, OLFM4 is an important player in the cellular process of inflammation, and it has important roles in innate immunity against bacterial infection, gastrointestinal inflammation, and cancer [17,31].…”

Section: Introductionmentioning

confidence: 99%

New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease

Bertran

Jorba

Barrientos-Riosalido

et al. 2022

IJMS

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Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, and negative associations with weight and jejunal Toll-like receptors (TLR4) and TLR5 expression. Regarding jejunal OLFM4, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal TLR9. In conclusion, OLFM2 in the liver seems to play a relevant role in NAFLD progression, while OLFM4 in the jejunum could be involved in gut dysbiosis-related inflammatory events.

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Section: Introductionmentioning

confidence: 99%

New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease

Bertran

Jorba

Barrientos-Riosalido

et al. 2022

IJMS

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“…As having a critical role in regulating cholesterol metabolism, LXRα plays a crucial part in atherosclerosis ( Zhang et al, 2012 ). In addition, NF-κB p65 and Nrf2 regulate hepatic lipogenesis and lipid homeostasis ( Daniel et al, 2021 , Huang et al, 2010 ). The overexpression of liver SREBP-1c, which activates FAS and ACLY, causes increased visceral adipose tissue and hepatic lipid accumulation ( Ito et al, 2013 , Zhang et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Effects of magnesium picolinate, zinc picolinate, and selenomethionine co-supplementation on reproductive hormones, and glucose and lipid metabolism-related protein expressions in male rats fed a high-fat diet

Şahin

Orhan

Küçük

et al. 2022

Food Chemistry: Molecular Sciences

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“…NF-κB seems to be the culprit in the production of inflammation in the lipid-overloaded environment [ 8 , 56 ]. The direct involvement of NF-κB in lipid regulation has been further demonstrated [ 37 , 57 , 58 ]. Hence, in this study, NF-κB signaling was examined by western blotting and found to be suppressed after WY-14,643 was administered, which is consistent with previous results [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC

et al. 2022

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Background Histologically, cytoplasmic deposits of lipids and glycogen are common in clear cell renal cell carcinoma (ccRCC). Owing to the significance of lipid deposition in ccRCC, numerous trials targeting lipid metabolism have shown certain therapeutic potential. The agonism of peroxisome proliferator-activated receptor-α (PPARα) via ligands, including WY-14,643, has been considered a promising intervention for cancers. Methods First, the effects of WY-14,643 on malignant behaviors were investigated in ccRCC in vitro. After RNA sequencing, the changes in lipid metabolism, especially neutral lipids and glycerol, were further evaluated. Finally, the underlying mechanisms were revealed. Results Phenotypically, the proliferation and migration of ccRCC cells treated with WY-14,643 were significantly inhibited in vitro. A theoretical functional mechanism was proposed in ccRCC: WY-14,643 mediates lipid consumption by recognizing carnitine palmitoyltransferase 1 A (CPT1A). Activation of PPARα using WY-14,643 reduces lipid deposition by increasing the CPT1A level, which also suppresses the NF-κB signaling pathway. Spatially, WY-14,643 binds and activates PPARα by targeting Gly335. Conclusion Overall, WY-14,643 suppresses the biological behaviors of ccRCC in terms of cell proliferation, migration, and cell cycle arrest. Furthermore, its anticancer properties are mediated by the inhibition of lipid accumulation, at least in part, through the PPARα/CPT1A axis by targeting Gly335, as part of the process, NF-κB signaling is also suppressed. Pharmacological activation of PPARα might offer a new treatment option for ccRCC.

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NF-κB p65 regulates hepatic lipogenesis by promoting nuclear entry of ChREBP in response to a high carbohydrate diet

Abstract: NF-κB p65 regulates hepatic lipogenesis by promoting nuclear entry of ChREBP in response to a high carbohydrate diet,

Cited by 22 publications

References 54 publications

New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease

New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease

Effects of magnesium picolinate, zinc picolinate, and selenomethionine co-supplementation on reproductive hormones, and glucose and lipid metabolism-related protein expressions in male rats fed a high-fat diet

WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC

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