Knocking Down CDKN2A in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process

Kahoul, Yasmina; Yao, Xi; Oger, Frédérik; Moreno, Maeva; Amanzougarene, Souhila; Derhourhi, Mehdi; Durand, Emmanuelle; Boutry, Raphaël; Bonnefond, Amélie; Froguel, Philippe; Dani, Christian; Annicotte, Jean-Sébastien; Breton, Christophe

doi:10.3390/cells12060870

Cited by 3 publications

(2 citation statements)

References 52 publications

(85 reference statements)

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“…ADRB3 also increased the number of lipid droplets, causing a transition from large to small droplets. This change can be attributed to the browning of white adipocytes, which have a smaller lipid structure than white adipocytes, and lipolysis [34][35][36]. Our findings validate this perspective.…”

Section: Discussionsupporting

confidence: 81%

The Role of β3-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs

Yang,

Ma,

Wang

et al. 2024

Cells

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After exposure to cold stress, animals enhance the production of beige adipocytes and expedite thermogenesis, leading to improved metabolic health. Although brown adipose tissue in rodents is primarily induced by β3-adrenergic receptor (ADRB3) stimulation, the activation of major β-adrenergic receptors (ADRBs) in pigs has been a topic of debate. To address this, we developed overexpression vectors for ADRB1, ADRB2, and ADRB3 and silenced the expression of these receptors to observe their effects on the adipogenic differentiation stages of porcine preadipocytes. Our investigation revealed that cold stress triggers the transformation of subcutaneous white adipose tissue to beige adipose tissue in pigs by modulating adrenergic receptor levels. Meanwhile, we found that ADRB3 promotes the transformation of white adipocytes into beige adipocytes. Notably, ADRB3 enhances the expression of beige adipose tissue marker genes, consequently influencing cellular respiration and metabolism by regulating lipolysis and mitochondrial expression. Therefore, ADRB3 may serve as a pivotal gene in animal husbandry and contribute to the improvement of cold intolerance in piglets.

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Section: Discussionsupporting

confidence: 81%

The Role of β3-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs

Yang,

Ma,

Wang

et al. 2024

Cells

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“…Additional, recent studies have highlighted the involvement of oxidative stress in the differentiation of beige fat. Elevated oxidative stress has been shown to boost UCP1 expression and the production of markers associated with beige fat ( Kahoul et al, 2023 ). Adipocytes, for proper functioning, rely on the activity of the nuclear receptor PPARγ.…”

Section: Discussionmentioning

confidence: 99%

Lactiplantibacillus plantarum N4 ameliorates lipid metabolism and gut microbiota structure in high fat diet-fed rats

Deng,

Zhang,

et al. 2024

Front. Microbiol.

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Lowing blood lipid levels with probiotics has good application prospects. This study aimed to isolate probiotics with hypolipidemic efficacy from homemade na dish and investigate their mechanism of action. In vitro experiments were conducted to determine the cholesterol-lowering ability of five isolates, with results showing that Lactiplantibacillus plantarum N4 exhibited a high cholesterol-lowering rate of 50.27% and significant resistance to acid (87%), bile salt (51.97%), and pepsin (88.28%) in simulated gastrointestinal fluids, indicating promising application prospects for the use of probiotics in lowering blood lipids. The findings from the in vivo experiment demonstrated that the administration of N4 effectively attenuated lipid droplet accumulation and inflammatory cell infiltration in the body weight and liver of hyperlipidemic rats, leading to restoration of liver tissue morphology and structure, as well as improvement in lipid and liver biochemical parameters. 16S analysis indicated that the oral administration of N4 led to significant alterations in the relative abundance of various genera, including Sutterella, Bacteroides, Clostridium, and Ruminococcus, in the gut microbiota of hyperlipidemia rats. Additionally, fecal metabolomic analysis identified a total of 78 metabolites following N4 intervention, with carboxylic acids and their derivatives being the predominant compounds detected. The transcriptomic analysis revealed 156 genes with differential expression following N4 intervention, leading to the identification of 171 metabolic pathways through Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Notably, the glutathione metabolism pathway, PPAR signaling pathway, and bile secretion pathway emerged as the primary enrichment pathways. The findings from a comprehensive multi-omics analysis indicate that N4 influences lipid metabolism and diminishes lipid levels in hyperlipidemic rats through modulation of fumaric acid and γ-aminobutyric acid concentrations, as well as glutathione and other metabolic pathways in the intestinal tract, derived from both the gut microbiota and the host liver. This research offers valuable insights into the therapeutic potential of probiotics for managing lipid metabolism disorders and their utilization in the development of functional foods.

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PPARγ and C/EBPα enable adipocyte differentiation upon inhibition of histone methyltransferase PRC2 in malignant tumors

Zhao,

Qian,

et al. 2024

Journal of Biological Chemistry

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Knocking Down CDKN2A in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process

Cited by 3 publications

References 52 publications

The Role of β3-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs

The Role of β3-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs

Lactiplantibacillus plantarum N4 ameliorates lipid metabolism and gut microbiota structure in high fat diet-fed rats

PPARγ and C/EBPα enable adipocyte differentiation upon inhibition of histone methyltransferase PRC2 in malignant tumors

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