Abstract
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake. Metabolomic analysis also demonstrated that DGLHD decreased isoleucine, adenosine, and cholesterol, increased glutamine levels in liver and visceral adipose tissue (VAT) of ob/ob mice. Importantly, DGLHD promoted the shift of pro-inflammatory to anti-inflammatory cytokines, suppressed T lymphocytes proliferation, and enhanced regulatory T cells (Tregs) differentiation. DGLHD also inhibited dendritic cells (DCs) maturation, attenuated DCs-stimulated T cells proliferation and secretion of IL-12p70 cytokine from DCs, and promoted the interaction of DCs with Tregs. Further studies indicated that the changed PI3K/Akt signaling pathway and elevated PPAR-γ expression were not only observed with the ameliorated glucose and lipid metabolism in adipocytes and hepatocytes, but also exhibited in DCs and T cells by DGLHD. Collectively, our results suggest that DGLHD exerts anti-insulin resistant and antisteatotic effects by improving abnormal immune and metabolic homeostasis. And DGLHD may be a novel approach to the treatment of obesity-related insulin resistance and hepatic steatosis.
Highlights
Obesity is defined as a pathological condition associated with numerous health problems and a reduced life expectancy, reaching epidemic proportions worldwide (Chang et al, 2015)
The ob/ob mouse carries a spontaneous mutation in the leptin gene, which results in a leptin deficiency, subsequently leading to hyperphagia, inactivity, obesity, insulin resistance, and hepatic steatosis (Kanuri and Bergheim, 2013)
Results showed that treatment with Dangguiliuhuang decoction (DGLHD) ameliorated hepatic steatosis, decreased free fatty acid (FFA), TG, and total cholesterol (TC) levels in liver and serum, and reduced the weight of liver and visceral adipose tissue (VAT) (Figure 1 and Figures S2C,D)
Summary
Obesity is defined as a pathological condition associated with numerous health problems and a reduced life expectancy, reaching epidemic proportions worldwide (Chang et al, 2015). DGLHD against Insulin Resistance and Fatty Liver because obesity can lead to insulin resistance, type 2 diabetes, fatty liver disease, cardiovascular disease, and certain forms of cancer (Hotamisligil, 2006). Impairment of insulin signaling is central to the development of insulin resistance, leading to the development of type 2 diabetes and liver disease. Accumulating evidence has shown that the impaired insulin signaling pathway, together with inflammatory responses, promotes hepatic lipid biosynthesis and steatosis, which in turn contribute to chronic hepatic inflammation and insulin resistance (Wang et al, 2016). Inflammation, insulin resistance, and hepatic steatosis are intertwined pathological events that are commonly presented in obese individuals
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