Sutherlandia frutescens targets adipose tissue mitochondrial metabolism

Sutherlandia frutescens (L.) R.Br. ex W.T.Aiton is an indigenous South African medicinal plant traditionally used to treat a number of ailments including diabetes. While previous in vivo studies have confirmed its anti-diabetic properties, the precise molecular mechanism of action has not been elucidated. In the present study we have established that S. frutescens treatment specifically attenuates a number of adipose tissue related paramaters, including circulatory and adipose tissue free fatty acid and triglyceride levels. The lack of any significant changes in adipose tissue nitrotyrosine and plasma MCP-1, both classical markers for adipose inflammation, indicates that these effects are not attributable to anti-inflammatory properties. In 3T3-L1 preadipocytes, treatment led to a significant increase in the rate of glucose consumption despite the complete absence of triglyceride accumulation. This increased glucose consumption is reflected by a corresponding dose dependent increase in lactate production, suggesting an increased glycolytic flux in treated cells. Taken together our in vivo and in vitro findings are consistent with a hypothesis in which S. frutescens induces mitochondrial uncoupling in adipose tissue, resulting in a reduced efficacy of oxidative phosporylation and a consequent up-regulation of glycolysis. In this manner the carbon flux is redirected away from lipid synthesis resulting in both decreased free fatty acid production and triglyceride accumulation in adipose tissue. Increased markers for mitochondrial function, elevated levels of phosporylated AKT and the effects on PI3K regulated glucose uptake in 3T3-L1 treated cells provide further support that S. frutescens counteracts adipocyte dysfunction associated with the development of diabetes.

Keywords: Sutherlandia frutescens, adipose tissue, lipid metabolism, mitochondria