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Nanoparticles encapsulated with resveratrol induce browning of white adipocytes
Author(s) -
Overby Haley,
Zu Yujiao,
Wang Shu,
Zhao Ling
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.44.3
Subject(s) - browning , white adipose tissue , prdm16 , chemistry , resveratrol , adipose tissue , cytotoxicity , thermogenin , biochemistry , in vitro
Functional brown adipose tissue, including classical brown adipocytes and brown‐like or beige adipocytes, which develop within white adipose tissue (WAT) in response to various stimuli, has emerged as novel targets for obesity treatment and prevention. Through browning process, beige adipocytes are induced to express UCP‐1 and become capable of thermogenesis. Identifying nutritional strategies that increase UCP‐1 and induce browning within white adipocytes is key to unlocking browning potential. Resveratrol (Res) is a well‐known polyphenol found in the skins of grapes and other fruits such as berries with anti‐inflammatory, antioxidant, and anti‐carcinogenic properties. Nanotechnology has shown great promise in encapsulating polyphenols, such as Res, to increase their solubility and stability, consequently, bioactivities. In this study, Res encapsulated in biocompatible and biodegradable lipid nanoparticles (Nano‐Res) or liposomes (Lipo‐Res), along with free Res (Res) and their respective controls (Nano‐Void or Lipo‐Void respectively) were tested at three doses (5, 10, 20 μM) in 3T3‐L1 mouse pre‐adipocytes in a 7‐day differentiation process. At the end of differentiation, the cells were subjected to thermogenic activation by isoproterenol (ISO), a β‐adrenergic receptor agonist, or the control for 6 hours. Cytotoxicity of the treatments and mRNA expression of UCP‐1, brown (PPARγ, PGC1α, PRDM16, and Cidea), beige (CD137 and Tmem26), and white marker genes (IGFBP3), as well as mitochondria related genes (Cox4a, Uqrch, Nrf, and Tfam) were measured. We report that none of the treatments showed signs of cytotoxicity at 24‐hrs and minimal toxicity at 72‐hrs. Lipo‐Res and Nano‐Res significantly induced dose‐dependent increase of UCP‐1 mRNA expression under ISO stimulated conditions compared to the controls (p<0.05). At the low dose of 5 μM Lipo‐Res significantly stimulated UCP‐1 to a higher level than free Res (p<0.05). Under both basal (non‐ISO stimulated) and ISO stimulated conditions, both Lipo‐Res and Nano‐Res dose‐dependently decreased WAT marker IGFBP3 mRNA (p<0.05) while simultaneously increasing mRNA of beige marker CD137 and brown markers PRDM16 (p<0.05). Interestingly, Lipo‐Res significantly increased Cidea expression in ISO‐stimulated conditions (p<0.05); however, Nano‐Res (and Nano‐Void) decreased Cidea expression (p<0.05). Other beige markers and mitochondrial structural genes were increased by encapsulated Res, but did not reach significance compared to the controls. Taken together, our results demonstrate that nanoencapsulation enhances Res's bioactivities in inducing browning of white adipocytes. Our results point towards promising nutritional strategies for obesity treatment and prevention. Support or Funding Information The work has been supported by NIH 1R15AT008733 award.