Sterol regulatory element-binding proteins (SREBPs) are major
transcription factors regulating the expression of genes involved in biosynthesis of
cholesterol,
fatty acids, and
triglycerides. We investigated the effect of the specific SREBP suppressor
andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of
andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced
obesity. Our results showed that
andrographolide downregulated the expressions of SREBPs target genes and decreased cellular
lipid accumulation in vitro. Further,
andrographolide (100 mg/kg per day) attenuated HFD-induced
body weight gain and fat accumulation in liver or adipose tissues, and improved serum
lipid levels and
insulin or
glucose sensitivity in HFD-induced obese mice.
Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased
body-weight gain of the obese mice fed with a HFD. Consistently,
andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower
lipid levels and enhanced
insulin sensitivity. Taken together, our results indicated that
andrographolide ameliorated lipid metabolism and improved
glucose use in mice with HFD-induced
obesity.
Andrographolide has potential as a leading compound in the prevention or treatment of
obesity and
insulin resistance.