A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation
<b>Background</b>: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/5/714 |
| _version_ | 1827752870680723456 |
|---|---|
| author | Francesca Pacifici Gina Malatesta Caterina Mammi Donatella Pastore Vincenzo Marzolla Camillo Ricordi Francesca Chiereghin Marco Infante Giulia Donadel Francesco Curcio Annalisa Noce Valentina Rovella Davide Lauro Manfredi Tesauro Nicola Di Daniele Enrico Garaci Massimiliano Caprio David Della-Morte |
| author_facet | Francesca Pacifici Gina Malatesta Caterina Mammi Donatella Pastore Vincenzo Marzolla Camillo Ricordi Francesca Chiereghin Marco Infante Giulia Donadel Francesco Curcio Annalisa Noce Valentina Rovella Davide Lauro Manfredi Tesauro Nicola Di Daniele Enrico Garaci Massimiliano Caprio David Della-Morte |
| author_sort | Francesca Pacifici |
| collection | DOAJ |
| description | <b>Background</b>: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5<sup>+</sup>) to counteract white adipogenesis by promoting WAT browning. <b>Methods</b>: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5<sup>+</sup>, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. <b>Results</b>: A5<sup>+</sup> administration significantly reduced lipids’ accumulation in adipocytes when compared to control cells (<i>p</i> < 0.005). Similarly, A5<sup>+</sup> inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (<i>p</i> < 0.0001). We also found that A5<sup>+</sup> significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (<i>p</i> < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (<i>p</i> < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. <b>Conclusion</b>: Overall, these results demonstrated that the synergistic effect of compounds contained in A5<sup>+</sup> may be able to counteract adipogenesis and then obesity by inducing fat browning. |
| first_indexed | 2024-03-11T07:29:07Z |
| format | Article |
| id | doaj.art-c4789e558e814104bb7de77dd09b051f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T07:29:07Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c4789e558e814104bb7de77dd09b051f2023-11-17T07:27:11ZengMDPI AGCells2073-44092023-02-0112571410.3390/cells12050714A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK ActivationFrancesca Pacifici0Gina Malatesta1Caterina Mammi2Donatella Pastore3Vincenzo Marzolla4Camillo Ricordi5Francesca Chiereghin6Marco Infante7Giulia Donadel8Francesco Curcio9Annalisa Noce10Valentina Rovella11Davide Lauro12Manfredi Tesauro13Nicola Di Daniele14Enrico Garaci15Massimiliano Caprio16David Della-Morte17Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyLaboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, 00166 Rome, ItalyDepartment of Human Sciences and Quality of Life Promotion, San Raffaele University, 00166 Rome, ItalyLaboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, 00166 Rome, ItalyCell Transplant Center, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USADepartment of Human Sciences and Quality of Life Promotion, San Raffaele University, 00166 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, ItalyCovid Internal Medicine Unit, Department of Translational Medical Sciences, AOU Federico II, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, ItalyUOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Human Sciences and Quality of Life Promotion, San Raffaele University, 00166 Rome, ItalyLaboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, 00166 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy<b>Background</b>: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5<sup>+</sup>) to counteract white adipogenesis by promoting WAT browning. <b>Methods</b>: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5<sup>+</sup>, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. <b>Results</b>: A5<sup>+</sup> administration significantly reduced lipids’ accumulation in adipocytes when compared to control cells (<i>p</i> < 0.005). Similarly, A5<sup>+</sup> inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (<i>p</i> < 0.0001). We also found that A5<sup>+</sup> significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (<i>p</i> < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (<i>p</i> < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. <b>Conclusion</b>: Overall, these results demonstrated that the synergistic effect of compounds contained in A5<sup>+</sup> may be able to counteract adipogenesis and then obesity by inducing fat browning.https://www.mdpi.com/2073-4409/12/5/714polyphenolsbrowningadipogenesismitotic clonal expansionAMPKUCP1 |
| spellingShingle | Francesca Pacifici Gina Malatesta Caterina Mammi Donatella Pastore Vincenzo Marzolla Camillo Ricordi Francesca Chiereghin Marco Infante Giulia Donadel Francesco Curcio Annalisa Noce Valentina Rovella Davide Lauro Manfredi Tesauro Nicola Di Daniele Enrico Garaci Massimiliano Caprio David Della-Morte A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation Cells polyphenols browning adipogenesis mitotic clonal expansion AMPK UCP1 |
| title | A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation |
| title_full | A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation |
| title_fullStr | A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation |
| title_full_unstemmed | A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation |
| title_short | A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation |
| title_sort | novel mix of polyphenols and micronutrients reduces adipogenesis and promotes white adipose tissue browning via ucp1 expression and ampk activation |
| topic | polyphenols browning adipogenesis mitotic clonal expansion AMPK UCP1 |
| url | https://www.mdpi.com/2073-4409/12/5/714 |
| work_keys_str_mv | AT francescapacifici anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT ginamalatesta anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT caterinamammi anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT donatellapastore anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT vincenzomarzolla anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT camilloricordi anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT francescachiereghin anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT marcoinfante anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT giuliadonadel anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT francescocurcio anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT annalisanoce anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT valentinarovella anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT davidelauro anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT manfreditesauro anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT nicoladidaniele anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT enricogaraci anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT massimilianocaprio anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT daviddellamorte anovelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT francescapacifici novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT ginamalatesta novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT caterinamammi novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT donatellapastore novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT vincenzomarzolla novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT camilloricordi novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT francescachiereghin novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT marcoinfante novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT giuliadonadel novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT francescocurcio novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT annalisanoce novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT valentinarovella novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT davidelauro novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT manfreditesauro novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT nicoladidaniele novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT enricogaraci novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT massimilianocaprio novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation AT daviddellamorte novelmixofpolyphenolsandmicronutrientsreducesadipogenesisandpromoteswhiteadiposetissuebrowningviaucp1expressionandampkactivation |