Abstract
Obesity is a worldwide threat to public health in modern society, which may result from leptin resistance and disorder of thermogenesis. The present study investigated whether astragaloside IV (ASI) could prevent obesity in high-fat diet (HFD)-fed and db/db mice. In HFD-fed mice, ASI prevented body weight gain, lowered serum triglyceride and total cholesterol levels, mitigated liver lipid accumulation, reduced fat tissues and decreased the enlargement of adipose cells. In metabolic chambers, ASI lessened appetite of the mice, decreased their respiratory exchange ratio and elevated VCO2 and VO2 without altering circadian motor activity. Moreover, ASI modulated thermogenesis associated gene expressions in liver and brawn fat tissues, as well as leptin resistance evidenced by altered expressions of leptin, leptin receptor (ObR) or appetite associated genes. In SH-SY5Y cells, ASI enhanced leptin signaling transduction. However, in db/db mice, ASI did not change body weight gain and appetite associated genes. But it decreased serum triglyceride and total cholesterol levels as well as liver triglyceride. Meanwhile, it significantly modulated gene expressions of PPARα, PGC1-α, UCP2, ACC, SCD1, LPL, AP2, CD36 and SREBP-1c. Collectively, our study suggested that ASI could efficiently improve lipid metabolism in obese mice probably through enhancing leptin sensitivity and modulating thermogenic network.
Highlights
Astragali Radix, one of the most commonly used traditional Chinese medicine (TCM), is prepared from the roots of Astragalus membranaceus (Fisch) Bunge or Astragalus mongholicus Bunge
high-fat diet (HFD) significantly elevated the epididymal adipose weight and increased the ratio of adipose tissue to body weight in mice compared with the CD (Fig. 1D,E, p < 0.01 and p < 0.001), the effect of which was significantly counteracted by Astragaloside IV (ASI) treatment (Fig. 1D,E)
Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure, in which leptin resistance in most cases is responsible for the disturbance of body weight control[11]
Summary
Astragali Radix, one of the most commonly used traditional Chinese medicine (TCM), is prepared from the roots of Astragalus membranaceus (Fisch) Bunge or Astragalus mongholicus Bunge. It is widely used in coffee, tea substitutes and food, in places such as Europe, the Middle East and Asia[12,13]. The effects of ASI on prevention of the development of hyperlipidemia and alleviation of leptin resistance in high-fat diet (HFD)-fed C57BL/6 mice and db/db mice were investigated and the possible underlying mechanisms were discussed. Our results implicated the potential application of ASI and its derivatives in the prevention of obesity as anti-leptin resistance agents
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