Lipid balance must be just right to prevent development of severe liver damage

Osborne, Timothy F.; Espenshade, Peter J.

doi:10.1172/jci160326

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…The liver is considered the critical organ for fatty acid metabolism . SREBPs are activators of the complete liver cholesterol and fatty acid synthesis program. , Moreover, it is essential to note that the lipogenic enzymes acetyl-CoA carboxylase-1 (ACC1) and stearoyl-CoA desaturase-1 (SCD-1) are regulated by SREBPs . The ACBP is a vital lipid transport protein synthesizing intracellular lipids .…”

Section: Discussionmentioning

confidence: 99%

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge

Gao,

Liu,

et al. 2024

J. Agric. Food Chem.

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Increasing evidence indicates that maternal exposure to oxidized soybean oil (OSO) causes damage to the mother and offspring. The antioxidant resveratrol (Res) has a variety of health benefits. However, the protective effect of Res on mitigating offspring damage after maternal exposure to OSO and its mechanism remains unclear. Therefore, this study aimed to investigate the effect of Res on hepatic fatty acid metabolism and the jejunal barrier in suckling piglets after maternal OSO exposure. A total of 18 sows in late gestation were randomly assigned to three treatments. The sows were fed with a fresh soybean oil (FSO) diet, an OSO diet, or the OSO diet supplemented with 300 mg/kg Res (OSO + Res), respectively. The results showed that maternal supplementation of Res restored the mRNA levels of genes related to fatty acid metabolism and increased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in suckling piglets' livers under the OSO challenge. Moreover, the OSO + Res group restored the mRNA levels of occludin and claudin 4 in suckling piglet jejunum compared with the results of the OSO challenges. In summary, supplementation with Res improves hepatic fatty acid metabolism and intestinal barrier function of suckling piglets after maternal OSO challenge during late gestation and lactation.

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Section: Discussionmentioning

confidence: 99%

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge

Gao,

Liu,

et al. 2024

J. Agric. Food Chem.

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“…GSK3 promotes the degradation of mature SREBP-1c ( Cross et al, 1995 ), which mediates lipid metabolism ( Lagathu et al, 2006 ). SREBP-1c is a major regulator of fatty acid synthesis in the liver ( Osborne and Espenshade, 2022 ). It can control the amount of TG in vivo by regulating acetyl coenzyme A carboxylase 1 (ACC1), fatty acid synthase (FASN), stearoyl coenzyme A desaturase (SCD-1) and other enzymes or proteins related to fatty acid synthesis ( Wang et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet

Meng

Huo

et al. 2022

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is a nutritional metabolic disease. Artemisia capillaris (AC) is the above-ground dried part of Artemisia capillaris Thunb. or Artemisia scoparia Waldst. et Kit., a natural medicinal plant with pharmacological effects of heat-clearing and biliary-promoting. In order to evaluate the therapeutic effect of Artemisia capillaris on NAFLD and obesity, experiments were conducted using aqueous extracts of Artemisia capillaris (WAC) to intervene in NAFLD models in vivo and in vitro. In vivo experiments were performed using HFD-fed (high fat diet) C57BL/6 mice to induce NAFLD model, and in vitro experiments were performed using oleic acid to induce HepG2 cells to construct NAFLD cell model. H.E. staining and oil red O staining of liver tissue were used to observe hepatocytes. Blood biochemistry analyzer was used to detect serum lipid levels in mice. The drug targets and mechanism of action of AC to improve NAFLD were investigated by western blotting, qRT-PCR and immunofluorescence. The results showed that C57BL/6 mice fed HFD continuously for 16 weeks met the criteria for NAFLD in terms of lipid index and hepatocyte fat accumulation. WAC was able to reverse the elevation of serum lipid levels induced by high-fat diet in mice. WAC promoted the phosphorylation levels of PI3K/AKT and AMPK in liver and HepG2 cells of NAFLD mice, inhibited SREBP-1c expression, reduced TG and lipogenesis, and decreased lipid accumulation. In summary, WAC extract activates PI3K/AKT pathway, reduces SREBP-1c protein expression by promoting AMPK phosphorylation, and decreases fatty acid synthesis and TG content in hepatocytes. AC can be used as a potential health herb to improve NAFLD and obesity.

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“…SREBP1, a member of sterol regulatory element−binding proteins (SREBPs), regulates lipogenesis as main transcription factors in mammals. 26 Previous studies have shown that SREBP1 regulated transcription of genes involved in fatty acid metabolism (FADS2, SCD1, and FASN). 27−29 Cellular immunofluorescence of SREBP1 nuclear localization also revealed that DHA treatment significantly reduced SREBP1 occupancy in the nucleus (Figure 5H and Figure S4G).…”

Section: Dha Regulates the Transcription Of Lipid Metabolism-related ...mentioning

confidence: 99%

Docosahexaenoic Acid Alters Lipid Metabolism Processes via H3K9ac Epigenetic Modification in Dairy Goat

Wu,

Luo,

et al. 2023

J. Agric. Food Chem.

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Goat milk is increasingly recognized by consumers due to its high nutritional value, richness in short-and mediumchain fatty acids, and richness in polyunsaturated fatty acids (PUFA). Exogenous supplementation of docosahexaenoic acid (DHA) is an important approach to increasing the content of PUFA in goat milk. Several studies have reported benefits of dietary DHA in terms of human health, including potential against chronic diseases and tumors. However, the mechanisms whereby an increased supply of DHA regulates mammary cell function is unknown. In this study, we investigated the effect of DHA on lipid metabolism processes in goat mammary epithelial cells (GMEC) and the function of H3K9ac epigenetic modifications in this process. Supplementation of DHA promoted lipid droplet accumulation increased the DHA content and altered fatty acid composition in GMEC. Lipid metabolism processes were altered by DHA supplementation through transcriptional programs in GMEC. ChIP-seq analysis revealed that DHA induced genome-wide H3K9ac epigenetic changes in GMEC. Multiomics analyses (H3K9ac genomewide screening and RNA-seq) revealed that DHA-induced expression of lipid metabolism genes (FASN, SCD1, FADS1, FADS2, LPIN1, DGAT1, MBOAT2), which were closely related with changes in lipid metabolism processes and fatty acid profiles, were regulated by modification of H3K9ac. In particular, DHA increased the enrichment of H3K9ac in the promoter region of PDK4 and promoted its transcription, while PDK4 inhibited lipid synthesis and activated AMPK signaling in GMEC. The activation of the expression of fatty acid metabolism-related genes FASN, FADS2, and SCD1 and their upstream transcription factor SREBP1 by the AMPK inhibitor was attenuated in PDK4-overexpressing GMEC. In conclusion, DHA alters lipid metabolism processes via H3K9ac modifications and the PDK4-AMPK-SREBP1 signaling axis in goat mammary epithelial cells, providing new insights into the mechanism through which DHA affects mammary cell function and regulates milk fat metabolism.

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Lipid balance must be just right to prevent development of severe liver damage

Cited by 6 publications

References 16 publications

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge

Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet

Docosahexaenoic Acid Alters Lipid Metabolism Processes via H3K9ac Epigenetic Modification in Dairy Goat

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