ACAT2 Is a Novel Negative Regulator of Pig Intramuscular Preadipocytes Differentiation

Tian, Ye; Zhao, Yangyang; Yu, Wensai; Melak, Sherif; Niu, Ying‐Fang; Wei, Wei; Zhang, Lifan; Chen, Jie

doi:10.3390/biom12020237

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…LDLR is significantly upregulated in JXB pigs, which explains why the cholesterol content in LD muscle tissue of DDBJ pigs was considerably elevated in contrast with that in JXB pigs. ACAT2 reduces LDLR levels and disturbs the cholesterol metabolism homeostasis, thereby inhibiting the differentiation of preadipocytes in pig muscle tissue [37]. ACAT2 gene expression was significantly upregulated in JXB pigs; thus, we speculated whether inhibition of LDLR by ACAT2 could offset the high expression level of LDLR in JXB pigs.…”

Section: Discussionmentioning

confidence: 98%

Multi-Omics Reveals the Effect of Crossbreeding on Some Precursors of Flavor and Nutritional Quality of Pork

Chen,

Zhang,

Xiao

et al. 2023

Foods

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Over the last several decades, China has continuously introduced Duroc boars and used them as breeding boars. Although this crossbreeding method has increased pork production, it has affected pork quality. Nowadays, one of the primary goals of industrial breeding and production systems is to enhance the quality of meat. This research analyzed the molecular mechanisms that control the quality of pork and may be used as a guide for future efforts to enhance meat quality. The genetic mechanisms of cross-breeding for meat quality improvement were investigated by combining transcriptome and metabolome analysis, using Chinese native Jiaxing black (JXB) pigs and crossbred Duroc × Duroc × Berkshire × JXB (DDBJ) pigs. In the longissimus Dorsi muscle, the content of inosine monophosphate, polyunsaturated fatty acid, and amino acids were considerably higher in JXB pigs in contrast with that of DDBJ pigs, whereas DDBJ pigs have remarkably greater levels of polyunsaturated fatty acids than JXB pigs. Differentially expressed genes (DEGs) and differential metabolites were identified using transcriptomic and metabolomic KEGG enrichment analyses. Differential metabolites mainly include amino acids, fatty acids, and phospholipids. In addition, several DEGs that may explain differences in meat quality between the two pig types were found, including genes associated with the metabolism of lipids (e.g., DGKA, LIPG, and LPINI), fatty acid (e.g., ELOVL5, ELOVL4, and ACAT2), and amino acid (e.g., SLC7A2, SLC7A4). Combined with the DEGS-enriched signaling pathways, the regulatory mechanisms related to amino acids, fatty acids, and phospholipids were mapped. The abundant metabolic pathways and DEGs may provide insight into the specific molecular mechanism that regulates meat quality. Optimizing the composition of fatty acids, phospholipids, amino acids, and other compounds in pork is conducive to improving meat quality. Overall, these findings will provide useful information and further groundwork for enhancing the meat quality that may be achieved via hybrid breeding.

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Section: Discussionmentioning

confidence: 98%

Multi-Omics Reveals the Effect of Crossbreeding on Some Precursors of Flavor and Nutritional Quality of Pork

Chen,

Zhang,

Xiao

et al. 2023

Foods

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“…Studies have shown that the knockout of ACAT2 in mice decreases the expression of ACAT2, inhibiting CE synthesis and thereby reducing the VLDL content in the serum and TG deposition in the liver, and ACAT2 is an important potential target for the treatment of fatty liver . Zhang et al demonstrated that the overexpression of ACAT2 inhibits the differentiation of preadipocytes in porcine muscle by suppressing fat synthesis . In addition, the posttranslational modification of the ACAT2 protein is an important mechanism for regulating lipid homeostasis .…”

Section: Discussionmentioning

confidence: 99%

“…First, ACAT2 on the endoplasmic reticulum serves as a cholesterol content monitor in the body and exhibits high sensitivity to variations in cholesterol concentration, thereby actively participating in the intricate regulation of cholesterol homeostasis . Second, ACAT2 plays a crucial role in regulating very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) syntheses within the body, facilitating TG homeostasis in the liver through the efficient transportation of excessive TG from the liver to peripheral tissues. − Previous studies have demonstrated that ACAT2 knockout ameliorates diet-induced hypercholesterolemia and suppresses gallstone formation in mice . Several studies have also demonstrated that ACAT2 functions as a negative regulator of lipid synthesis, highlighting its potential as a therapeutic target for treating fatty liver. , In addition, the overexpression of ACAT2 inhibits the differentiation of prelipid adipocytes in porcine muscle, thereby impeding intermuscular lipid synthesis .…”

Section: Introductionmentioning

confidence: 99%

“…Second, ACAT2 plays a crucial role in regulating very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) syntheses within the body, facilitating TG homeostasis in the liver through the efficient transportation of excessive TG from the liver to peripheral tissues. − Previous studies have demonstrated that ACAT2 knockout ameliorates diet-induced hypercholesterolemia and suppresses gallstone formation in mice . Several studies have also demonstrated that ACAT2 functions as a negative regulator of lipid synthesis, highlighting its potential as a therapeutic target for treating fatty liver. , In addition, the overexpression of ACAT2 inhibits the differentiation of prelipid adipocytes in porcine muscle, thereby impeding intermuscular lipid synthesis . The liver serves as a crucial site for the expression of ACAT2, playing a pivotal role in both cholesterol and TG synthesis and metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Lentinan Ameliorates β-Hydroxybutyrate-Induced Lipid Metabolism Disorder in Bovine Hepatocytes by Upregulating the Expression of Acetyl-coenzyme A Acetyltransferase 2

Zhou,

Ma,

Meng

et al. 2024

J. Agric. Food Chem.

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Ketosis in dairy cows is often accompanied by the dysregulation of lipid homeostasis in the liver. Acetyl-coenzyme A acetyltransferase 2 (ACAT2) is specifically expressed in the liver and is important for regulating lipid homeostasis in ketotic cows. Lentinan (LNT) has a wide range of pharmacological activities, and this study investigates the protective effects of LNT on βhydroxybutyrate (BHBA)-induced lipid metabolism disorder in bovine hepatocytes (BHECs) and elucidates the underlying mechanisms. BHECs were first pretreated with LNT to investigate the effect of LNT on BHBA-induced lipid metabolism disorder in BHECs. ACAT2 was then silenced or overexpressed to investigate whether this mediated the protective action of LNT against BHBA-induced lipid metabolism disorder in BHECs. Finally, BHECs were treated with LNT after silencing ACAT2 to investigate the interaction between LNT and ACAT2. LNT pretreatment effectively enhanced the synthesis and absorption of cholesterol, inhibited the synthesis of triglycerides, increased the expression of ACAT2, and elevated the contents of very low-density lipoprotein and low-density lipoprotein cholesterol, thereby ameliorating BHBA-induced lipid metabolism disorder in BHECs. The overexpression of ACAT2 achieved a comparable effect to LNT pretreatment, whereas the silencing of ACAT2 aggravated the effect of BHBA on inducing disorder in lipid metabolism in BHECs. Moreover, the protective effect of LNT against lipid metabolism disorder in BHBA-induced BHECs was abrogated upon silencing of ACAT2. Thus, LNT, as a natural protective agent, can enhance the regulatory capacity of BHECs in maintaining lipid homeostasis by upregulating ACAT2 expression, thereby ameliorating the BHBA-induced lipid metabolism disorder.

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“…Overexpression of CREB-regulated transcription coactivator 3 (CRTC3) gene has been shown to promote adipogenic differentiation of porcine intramuscular adipocytes by activating the Ca2+-cAMP signaling pathway [214]. On the other hand, Tian et al suggest that acetyl-CoA acetyltransferase 2 (ACAT2) negatively affects the differentiation of porcine IMPs through the regulation of srebp2/ldlr, cebpα, and PPARγ signaling involved in cholesterol metabolism [215] A recent study showed that knockdown of Krüppel-like factor 7 (KLF7) inhibits differentiation of goat IMPs, i.e., there is a reduction in the accumulation of lipid droplets, as well as expression of adipogenic markers. On the other hand, Huang et al showed that fibroblast growth factor 9 (FGF9) inhibits the differentiation of goat intramuscular adipocytes by interacting with the fibroblast growth factor receptor 2 (FGFR2), thus regulating PPARγ and preadipocyte factor 1 (Pref1) [216].…”

Section: Biochemical Cuesmentioning

confidence: 99%

Using Vertebrate Stem and Progenitor Cells for Cellular Agriculture, State-of-the-Art, Challenges, and Future Perspectives

et al. 2022

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Global food systems are under significant pressure to provide enough food, particularly protein-rich foods whose demand is on the rise in times of crisis and inflation, as presently existing due to post-COVID-19 pandemic effects and ongoing conflict in Ukraine and resulting in looming food insecurity, according to FAO. Cultivated meat (CM) and cultivated seafood (CS) are protein-rich alternatives for traditional meat and fish that are obtained via cellular agriculture (CA) i.e., tissue engineering for food applications. Stem and progenitor cells are the building blocks and starting point for any CA bioprocess. This review presents CA-relevant vertebrate cell types and procedures needed for their myogenic and adipogenic differentiation since muscle and fat tissue are the primary target tissues for CM/CS production. The review also describes existing challenges, such as a need for immortalized cell lines, or physical and biochemical parameters needed for enhanced meat/fat culture efficiency and ways to address them.

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ACAT2 Is a Novel Negative Regulator of Pig Intramuscular Preadipocytes Differentiation

Cited by 7 publications

References 36 publications

Multi-Omics Reveals the Effect of Crossbreeding on Some Precursors of Flavor and Nutritional Quality of Pork

Multi-Omics Reveals the Effect of Crossbreeding on Some Precursors of Flavor and Nutritional Quality of Pork

Lentinan Ameliorates β-Hydroxybutyrate-Induced Lipid Metabolism Disorder in Bovine Hepatocytes by Upregulating the Expression of Acetyl-coenzyme A Acetyltransferase 2

Using Vertebrate Stem and Progenitor Cells for Cellular Agriculture, State-of-the-Art, Challenges, and Future Perspectives

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