Botanical extracts from St. John's Wort inhibit adipogenesis and induce insulin resistance

Abstract

Adipocytes are insulin sensitive cells that play a major role in energy homeostasis. Obesity is the primary disease of fat cells and a major risk factor for the development of Type II diabetes, cardiovascular disease, and metabolic syndrome. Obesity and its related disorders results in dysregulation of the mechanisms that control adipocyte gene expression and function. To identify potential novel therapeutic modulators of adipocytes, we screened 425 botanical extracts for their ability to modulate adipogenesis and insulin sensitivity. We observed that less than 2% of the extracts had substantial effects on adipocyte differentiation. Two of the positive hit botanicals we screened that inhibited adipogenesis were extracts from St. John's Wort (SJW). Our studies revealed that two different SJW extracts inhibited adipogenesis as judged by lipid staining and marker gene expression. We also examined the effects of these SJW extracts on insulin sensitivity in mature adipocytes. One of the SJW extracts substantially inhibited insulin sensitive glucose uptake in a time and dose dependent manner. SJW is commonly used in the treatment of depression. However, our studies have revealed that SJW may have a negative impact on adipocyte related diseases by limiting adipocyte differentiation of preadipocytes and significantly inducing insulin resistance in mature fat cells.