The effect of synapic acid on the proliferation, differentiation and migration of 3T3-L1 preadipocytes: the role of the hedgehog signal mechanism

Obesity, one of the biggest health problems of today, is associated with many pathological conditions such as type II diabetes, hypertension, cancer, gallbladder disease and atherosclerosis. One of the most important mechanisms in the development of obesity is the differentiation of preadipocytes in the adipose tissue stromal fraction into mature adipocytes. Although the pathways involved in preadipocyte differentiation are still not fully known, it is a complex process involving many transcription factors. In cereals such as rice and oats; sinapic acid, a phenolic compound found in high concentrations in some spices such as rosemary and some fruits and vegetables such as strawberries, broccoli and lemons, has been shown to have effects on differentiation in studies conducted in different cell cultures such as HKE293 human kidney epithelial cells and NIH/3T3 fibroblast cells, but its mechanism of action has not been fully elucidated. In a recent study, it was shown that herbal extract consisting of phenolic compounds, including sinapic acid, prevented weight gain in mice fed a high-fat diet and inhibited differentiation in 3T3-L1 preadipocytes by activating AMPK signaling pathway. In a study on 3T3-L1 preadipocytes, extracts of 7 different hydroxycinnamic acid derivatives, including sinapic acid, obtained from blueberry and raspberry, it has been shown to inhibit differentiation by reducing PPARγ, C/EBPα, SREBP1, aP2, FAS, LPL gene expressions that are involved in differentiation. In another study on 3T3-L1 adipocytes, it was observed that sulforafen inhibited adipocyte differentiation and prevented adipocyte hyperplasia by activating the Hedgehog signaling pathway. Therefore, substances that activate the Hedgehog signaling pathway may be effective agents that can be used to prevent or treat the development of obesity. It has been shown that sinapic acid can suppress differentiation in 3T3-L1 cells via AMPK or MAPK signaling pathways, but there is no study showing whether Hedgehog signaling pathway is involved in its effects on preadipocyte differentiation. Therefore, our study was conducted to clarify the effects of sinapic acid at different concentrations and at different time points of the differentiation process on proliferation, differentiation and migration in 3T3-L1 cells and whether this effect is mediated by the Hedgehog signaling pathway.