An Investigation Into the Most Effective Approaches for Teaching Non-technical Skills to Medical Students at the Undergraduate Level: an Exploration of the Role of Simulation-based Education

Obesity and associated comorbidities such as cardiac diseases have become a major public health problem for today’s societies. There has been an increased focus on the use of natural compounds to combat this growing pandemic. Many studies have concluded that dietary polyphenolic flavonoids can reduce the development of mature adipocytes, a prerequisite for obesity, but little is known about the precise mechanisms and stages of flavonoid action. Furthermore, there is a scarcity of literature on the effect of flavonoids on adipogenesis using human cell strains.
Human preadipocytes (SGBS cells), a novel adipogenesis model, were treated with a range of concentrations of quercetin, kaempferol, galangin, chrysin, luteolin and apigenin representing the flavonoid classes of flavanols and flavones. Treated preadipocytes were tested for viability, proliferation, differentiation and dedifferentiation. Assessment protocols used included MTT assays, microscopic cell counts, oil red O assays, morphological analysis, qPCR analysis and western blots. Finally, to simulate the effects of dietary metabolism to glucuronides, culture medium from quercetin treated human Caco2-TC7 colorectal cancer cells was analysed by HPLC.

Results showed a relationship between the number of hydroxyl groups present in flavonoids and their effect on both preadipocyte proliferation and conversion to committed adipocytes. A selection of flavone and flavanol combinations showed synergistic effect on proliferation and an additive effect on differentiation. Genes related to the apoptotic pathway (BIM and BAD) were significantly upregulated (p<0.05) whereas proliferation genes (Ki67 and TPX2) were downregulated on cells treated with supra-physiological concentrations of selected flavonoids. Insulin regulating genes, PPAR gamma, Leptin and Adiponectin were significantly upregulated (p<0.05) in differentiated cells treated with selected flavonoids. Whilst physiological concentrations of flavonoids appeared to increase preadipocyte proliferation (p<0.05), the increase was not sustained during differentiation.

It was also shown that the impact of flavonoids on differentiation was independent of the stage at which the flavonoid was introduced during the course of differentiation. Flavonoid conversion to glucuronides was shown to be inefficient (< 5%) and so did not warrant further investigation. More specifically, protein and gene analysis suggested that flavonoids reduce both preadipocyte proliferation and differentiation through Akt, Erk, SREBP1c and CEBP-β associated pathways. There were suggestions of increased browning of cells treated with sub-physiological flavonoid concentrations through the upregulation of the uncoupling protein 1 (UCP1), a mitochondrial protein associated with adaptive thermogenesis.

In sum, the study points to great potential of flavonoids being used to reduce fat mass through insulin regulation, browning and dedifferentiation.