Abstract
Berberine (BBR) is the main active ingredient of a traditional Chinese herb Coptis chinensis. It has been reported to exhibit beneficial effects in treating diabetes and obesity. However, the underlying mechanism has not been fully elucidated. Adipose tissue fibrosis is a hallmark of obesity-associated adipose tissue dysfunction. HIF-1α plays a key role in adipose tissue fibrosis, which closely linked to metabolic dysfunction in obese state. We hypothesized that BBR may alleviate obesity-induced adipose tissue fibrosis and associated metabolic dysfunction through inhibition of HIF-1α. To test this hypothesis, we treated high fat diet (HFD) feeding mice with different dose of BBR (100 mg/kg, 200 mg/kg, and 300 mg/kg) for 8 weeks. We found that BBR treatment greatly decreased the body weight gain and reduced insulin resistance induced by HFD. Data also revealed that BBR improved histologic fibrous of epididymal white adipose tissue (eWAT) and was accompanied with inhibition of the abnormal synthesis and deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin. We also found that BBR treatment suppressed the expression of HIF-1α and decreased the mRNA expression of LOX in epididymal adipose tissue, which plays a key role in fibrosis development. Taken together, these results suggest that BBR can regulate metabolic homeostasis and suppress adipose tissue fibrosis through inhibiting the expression of HIF-1α.
Highlights
Obesity has become a severe health issue and causes enormous economic burden worldwide
We found that mice treated with BBR show a beneficial metabolically phenotype, such as a decrease in body weight gain and reduced insulin resistance, which was accompanied by decreased hypoxia-inducible factor 1α (HIF-1α) accumulation and improved adipose tissue fibrosis
We calculated the area under the curve for Glucose Tolerance Test (GTT) (Figure 1(d)) and Insulin Tolerance Test (ITT) (Figure 1(f)), which clearly showed that BBR treatment significantly improved glucose tolerance and insulin sensitivity
Summary
Obesity has become a severe health issue and causes enormous economic burden worldwide. A study from 195 countries worldwide showed that the prevalence of obesity has doubled since 1980. The obesity rates for children and adults were 5% and 12%, respectively, and these results are similar with the prevalence of type 2 diabetes worldwide [1]. Obese individuals are more likely to develop metabolic disorders, such as type 2 diabetes and cardiovascular diseases, as well as chronic inflammatory diseases [2]. Dietary and life style changes are recommended for obese people. It only works for a small percent of people. A better understanding of the pathological changes of obesity would provide potential new target for antiobese therapy
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