miRNAs and Novel Food Compounds Related to the Browning Process

Lorente‐Cebrián, Silvia; Herrera, Katya; Milagro, Fermı́n I.; Sánchez, Juana; Garza, Ana Laura de la; Castro, Heriberto

doi:10.3390/ijms20235998

Cited by 7 publications

(4 citation statements)

References 235 publications

(217 reference statements)

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“…There are a number of published studies showing the health benefits induced by the “browning” of white adipose tissue [ 52 , 53 , 54 , 55 ]. In addition, there are published studies of Omega-3 fish oil converting WAT to beige fat [ 56 ] and even novel food compounds assisting in the browning of WAT [ 57 ]. Our group has focused on the upregulation of heme oxygenase by eicosanoids in vivo [ 3 , 58 ] and in vitro [ 44 ], which has been very effective in the conversion of WAT to beige fat as well as the amelioration of NAFLD and NASH in the liver [ 5 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Cold-Pressed Nigella Sativa Oil Standardized to 3% Thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation, and Markers of Insulin Resistance Accompanied with Conversion of White to Beige Fat in Mice

et al. 2020

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Excessive lipid accumulation in white adipose tissue (WAT) results in adipocyte hypertrophy and chronic low-grade inflammation, which is the major cause of obesity-associated insulin resistance and consequent metabolic disease. The development of beige adipocytes in WAT (browning of WAT) increases energy expenditure and has been considered as a novel strategy to counteract obesity. Thymoquinone (TQ) is the main bioactive quinone derived from the plant Nigella Sativa and has antioxidative and anti-inflammatory capacities. Fish oil omega 3 (ω3) enhances both insulin sensitivity and glucose homeostasis in obesity, but the involved mechanisms remain unclear. The aim of this study is to explore the effects of TQ and ω3 PUFAs (polyunsaturated fatty acids) on obesity-associated inflammation, markers of insulin resistance, and the metabolic effects of adipose tissue browning. 3T3-L1 cells were cultured to investigate the effects of TQ and ω3 on the browning of WAT. C57BL/6J mice were fed a high-fat diet (HFD), supplemented with 0.75% TQ, and 2% ω3 in combination for eight weeks. In 3T3-L1 cells, TQ and ω3 reduced lipid droplet size and increased hallmarks of beige adipocytes such as uncoupling protein-1 (UCP1), PR domain containing 16 (PRDM16), fibroblast growth factor 21 (FGF21), Sirtuin 1 (Sirt1), Mitofusion 2 (Mfn2), and heme oxygenase 1 (HO-1) protein expression, as well as increased the phosphorylation of Protein Kinase B (AKT) and insulin receptors. In the adipose tissue of HFD mice, TQ and ω3 treatment attenuated levels of inflammatory adipokines, Nephroblastoma Overexpressed (NOV/CCN3) and Twist related protein 2 (TWIST2), and diminished adipocyte hypoxia by decreasing HIF1α expression and hallmarks of beige adipocytes such as UCP1, PRDM16, FGF21, and mitochondrial biogenesis markers Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), Sirt1, and Mfn2. Increased 5′ adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation and HO-1 expression were observed in adipose with TQ and ω3 treatment, which led to increased pAKT and pIRS1 Ser307 expression. In addition to the adipose, TQ and ω3 also increased inflammation and markers of insulin sensitivity in the liver, as demonstrated by increased phosphorylated insulin receptor (pIR tyr972), insulin receptor beta (IRβ), UCP1, and pIRS1 Ser307 and reduced NOV/CCN3 expression. Our data demonstrate the enhanced browning of WAT from TQ treatment in combination with ω3, which may play an important role in decreasing obesity-associated insulin resistance and in reducing the chronic inflammatory state of obesity.

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Section: Discussionmentioning

confidence: 99%

Cold-Pressed Nigella Sativa Oil Standardized to 3% Thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation, and Markers of Insulin Resistance Accompanied with Conversion of White to Beige Fat in Mice

et al. 2020

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“…In adipose tissues, miRNAs play an important role in regulating the pathways that control a range of processes including adipocyte differentiation, insulin signaling and glucose homeostasis (8). Recent studies have demonstrated that some miRNA directly target and regulate thermogenic genes of brown adipocyte development and the beiging of white adipocytes (9)(10)(11). Among adipose expressed miRNA, miR-182-5p is highly enriched in differentiated brown adipocytes compared to non-differentiated cells (12).…”

Section: Introductionmentioning

confidence: 99%

The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis

Meng¹,

Xiao²,

Liang³

et al. 2021

JCI Insight

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A dynamically regulated microenvironment, which is mediated by crosstalks between adipocytes and neighboring cells, is critical for adipose tissue homeostasis and function. However, information on key molecules and/or signaling pathways regulating the crosstalks remains limited. In this study, we identify adipocyte miR-182-5p as a crucial anti-obesity molecule that stimulates beige fat thermogenesis by promoting the crosstalk between adipocytes and macrophages. miR-182-5p is highly enriched in thermogenic adipocytes and its expression is markedly stimulated by cold exposure in mice. In contrast, miR-182-5p expression is significantly reduced in adipose tissues of obese humans and mice. Knockout of miR-185-5p decreased cold-induced beige fat thermogenesis whereas overexpression of miR-185-5p increased beiging and thermogenesis in mice. Mechanistically, miR-182-5p promotes FGF21 expression and secretion in adipocytes by suppressing Nr1d1 at 5'UTR, which in turn stimulates acetylcholine synthesis and release in macrophages. Increased acetylcholine expression activates the nicotine acetylcholine receptor in adipocytes, which stimulates PKA signaling and consequent thermogenic gene expression. Our study reveals a key role of the miR-182-5p/FGF21/acetylcholine/acetylcholine receptor axis that mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis. Activation of the miR-182-5p-induced signaling pathway in adipose tissue may be an effective approach to ameliorate obesity and associated metabolic diseases.

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“…It is suggested that white adipose tissue (WAT) could enhance thermogenesis by the process of ‘browning’. MiRNAs also modulate brite/brown adipogenesis [ 67 ], intriguingly, in which regulatory miRNAs are almost encompassed in breast cancer-associated miRNA list. It suggests that adipose tissue regulation and breast cancer have specific similarity at regulatory miRNA level.…”

Section: Discussionmentioning

confidence: 99%

Human microRNA similarity in breast cancer

Jing

2021

Bioscience Reports

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MicroRNAs (miRNAs) play important roles in a variety of human diseases, including breast cancer. A number of miRNAs are up- and down-regulated in breast cancer. However, little is known about miRNA similarity and similarity network in breast cancer. Here, a collection of 272 breast cancer-associated miRNA precursors were utilized to calculate similarities of sequences, target genes, pathways and functions and construct a combined similarity network. Well-characterized miRNAs and their similarity network were highlighted. Interestingly, miRNA sequence-dependent similarity networks were not identified in spite of sequence-target gene association. Similarity networks with minimum and maximum number of miRNAs originate from pathway and mature sequence, respectively. The breast cancer-associated miRNAs were divided into 7 functional classes (classes I-VII) followed by disease enrichment analysis and novel miRNA-based disease similarities were found. The finding would provide insight into miRNA similarity, similarity network and disease heterogeneity in breast cancer.

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miRNAs and Novel Food Compounds Related to the Browning Process

Cited by 7 publications

References 235 publications

Cold-Pressed Nigella Sativa Oil Standardized to 3% Thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation, and Markers of Insulin Resistance Accompanied with Conversion of White to Beige Fat in Mice

Cold-Pressed Nigella Sativa Oil Standardized to 3% Thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation, and Markers of Insulin Resistance Accompanied with Conversion of White to Beige Fat in Mice

The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis

Human microRNA similarity in breast cancer

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