METHODS: Presently, we provide a review of key studies evaluating the effects of dietary flavonoids in different stages of adipocyte development with a particular emphasis on the investigations that explore the underlying mechanisms of action of these compounds in human or animal cell lines as well as animal models.
RESULTS: Flavonoids have been shown to regulate several pathways and affect a number of molecular targets during specific stages of adipocyte development. Although most of the studies reveal anti-adipogenic effect of flavonoids, some flavonoids demonstrated proadipogenic effect in mesenchymal stem cells or preadipocytes.
CONCLUSION: The anti-adipogenic effect of flavonoids is mainly via their effect on regulation of several pathways such as induction of apoptosis, suppression of key adipogenic transcription factors, activation of AMPK and Wnt pathways, inhibition of clonal expansion, and cell-cycle arrest.
METHODS: We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library.
RESULTS: We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC's adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening.
CONCLUSION: Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.