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other·endocrinology, nutrition, preclinical research, biomedical research, micronutrients·PMC10153092

Naringenin and β-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis

Frontiers in Endocrinology · 9 authors, 7 centres

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TL;DR

Human preadipocytes from donors with obesity were differentiated in culture and treated with naringenin and β-carotene for seven days. The combination synergistically upregulated thermogenesis genes including UCP1, glucose metabolism genes, and hormone-stimulated lipolysis compared to naringenin alone.

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Human preadipocytes from donors with obesity were differentiated in culture and treated with 8 µM naringenin plus 2 µM β-carotene for seven days. β-carotene synergistically enhanced UCP1 expression and glucose metabolism genes including GLUT4 and adiponectin compared to naringenin alone. Protein levels of PPARα, PPARγ, and PGC-1α were upregulated. Transcriptome sequencing revealed NRBC induced non-UCP1 energy expenditure pathways including triglyceride cycling and creatine kinases. Eight receptors linked to lipolysis or thermogenesis were upregulated, and parathyroid hormone elicited the greatest lipolytic response. RXRγ expression was induced ten-fold.

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other

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endocrinology

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ORIGINAL PAPER

PMC10153092

Naringenin and β-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis

Frontiers in Endocrinology

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ABSTRACT

Abstract Introduction Naringenin, a peroxisome proliferator-activated receptor (PPAR) activator found in citrus fruits, upregulates markers of thermogenesis and insulin sensitivity in human adipose tissue. Our pharmacokinetics clinical trial demonstrated that naringenin is safe and bioavailable, and our case report showed that naringenin causes weight loss and improves insulin sensitivity. PPARs form heterodimers with retinoic-X-receptors (RXRs) at promoter elements of target genes. Retinoic acid is an RXR ligand metabolized from dietary carotenoids. The carotenoid β-carotene reduces adiposity and insulin resistance in clinical trials. Our goal was to examine if carotenoids strengthen the beneficial effects of naringenin on human adipocyte metabolism. Methods Human preadipocytes from donors with obesity were differentiated in culture and treated with 8µM naringenin + 2µM β-carotene (NRBC) for seven days. Candidate genes involved in thermogenesis and glucose metabolism were measured as well as hormone-stimulated lipolysis. Results We found that β-carotene acts synergistically with naringenin to boost UCP1 and glucose metabolism genes including GLUT4 and adiponectin, compared to naringenin alone. Protein levels of PPARα, PPARγ and PPARγ-coactivator-1α, key modulators of thermogenesis and insulin sensitivity, were also upregulated after treatment with NRBC. Transcriptome sequencing was conducted and the bioinformatics analyses of the data revealed that NRBC induced enzymes for several non-UCP1 pathways for energy expenditure including triglyceride cycling, creatine kinases, and Peptidase M20 Domain Containing 1 (PM20D1). A comprehensive analysis of changes in receptor expression showed that NRBC upregulated eight receptors that have been linked to lipolysis or thermogenesis including the β1-adrenergic receptor and the parathyroid hormone receptor. NRBC increased levels of triglyceride lipases and agonist-stimulated lipolysis in adipocytes. We observed that expression of RXRγ, an isoform of unknown function, was induced ten-fold after treatment with NRBC. We show that RXRγ is a coactivator bound to the immunoprecipitated PPARγ protein complex from white and beige human adipocytes. Discussion There is a need for obesity treatments that can be administered long-term without side effects. NRBC increases the abundance and lipolytic response of multiple receptors for hormones released after exercise and cold exposure. Lipolysis provides the fuel for thermogenesis, and these observations suggest that NRBC has therapeutic potential. Keywords: UCP1, naringenin, carotenoid, PPARγ, RXRγ, PPARα, adiponectin, lipolysis

CITATION EXPORT

Ann A Coulter, Frank L Greenway, Dachuan Zhang et al.. Naringenin and β-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis. Frontiers in Endocrinology. (2023). https://doi.org/10.3389/fendo.2023.1148954

AUTHORS

9 · 7 CENTRES

Ann A Coulter, Frank L Greenway, Dachuan Zhang, Sujoy Ghosh, Cathryn R Coulter, Sarah L James, Yanlin He, Luke A Cusimano, Candida J Rebello

1 Computational Biology, Pennington Biomedical Research Center, Baton Rouge, LA, United States
2 Clinical Trials, Pennington Biomedical Research Center, Baton Rouge, LA, United States
3 Biostatistics, Pennington Biomedical Research Center, Baton Rouge, LA, United States
4 Adjunct Faculty, Pennington Biomedical Research Center, Baton Rouge, LA, United States
5 Brain Glycemic and Metabolism Control, Pennington Biomedical Research Center, Baton Rouge, LA, United States
6 Cusimano Plastic and Reconstructive Surgery, Baton Rouge, LA, United States
7 Nutrition and Chronic Disease, Pennington Biomedical Research Center, Baton Rouge, LA, United States