Differential effects of dietary flavonoids on adipogenesis

Abstract

Propose: Obesity is a fast growing epidemic worldwide. During obesity, the increase in adipose tissue mass arise from two different mechanisms, namely, hyperplasia and hypertrophy. Hyperplasia which is the increase in adipocyte number is characteristic of severe obese patients. Recently, there has been much interest in targeting adipogenesis as therapeutic strategy against obesity. Flavonoids have been shown to regulate several pathways and affect a number of molecular targets during specific stages of adipocyte development.

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.

Keywords: Adipocyte; Adipogenesis; Flavonoids; Hyperplasia; Obesity.

Fig. 1

Adipogenesis network. The process of adipogenesis begin with the activation of transcription factors, C/EBPβ and C/EBPδ. These transcription factors function during the early adipogenesis program to regulate the expression of the two master regulators of adipogenesis, PPAR-γ and C/EBPα. The expression of adipogenic genes is regulated by binding of PPARG as a heterodimer with RXRα, where C/EBPα and C/EBPβ occupy the C/EBP response elements. Several other important transcriptional factors play a role in control of adipogenesis. Some transcriptional factors including KLF5 and CREB have a positive role in adipogenesis, whereas other transcriptional factors such as KLF2 and GATA2/3 suppress adipogenesis. C/EBP CCAT/enhancer-binding protein, PPARG peroxisome proliferator-activated receptor-gamma, ERK extracellular signal-regulated kinase, KLFs Kruppel-like factors, CREB cyclic AMP response element-binding protein, FOXO1 forkhead box O1, TCF/LEF T-cell factor/lymphoid enhancer factor, MAPK mitogen-activated protein kinase, Wnt wingless-type MMTV integration site family, PKA protein kinase A, GR glucocorticoid receptor, DR1 direct repeat type 1 element

Fig. 2

MiRNAs in adipogenesis. MiRNAs influence adipogenesis during determination phase, which is the conversion of mesenchymal stem cell to preadipocytes, clonal expansion, and terminal differentiation of preadipocyte to mature adipocyte. MAPK mitogen-activated protein kinase, ERK extracellular signal-regulated kinase, MSC mesenchymal stem cell, cAMP cyclic adenosine monophosphate, CREB cAMP response element-binding, WNT wingless and INT-1, TCF T-cell-specific transcription factor, PPAR peroxisome proliferator-activated receptor, C/EBP CCAAT/enhancer-binding protein, KLF Kruppel-like factor, IRS insulin receptor substrate, PKB protein kinase B, GSK glycogen synthase kinase 3

Fig. 3

Basic structure of flavonoids