Abstract
Berberine (BBR), which is an active component of Coptis chinensis Franch, has been reported to improve glucose metabolism and insulin resistance in animal and human studies, predominantly via activation of the 5′-adenosine monophosphate kinase (AMPK) pathway and suppression of the inflammation response. However, the mechanisms underlying the effects of BBR on AMPK and inflammation remain unclear. In this present study, we found that BBR upregulated SIRT1 expression in 3T3L-1 adipocytes and adipose tissue. Inhibition of SIRT1 blunted the BBR-induced increase in glucose consumption and uptake in adipocytes. The BBR-induced activation of the AMPK pathway and AKT phosphorylation in adipocytes and adipose tissue were also attenuated by inhibition or knockout of Sirt1. The BBR-induced improvement of systemic insulin sensitivity was impaired by Sirt1 knockout in HFD-induced obese mice. The suppressing effects of BBR on systemic and local inflammatory responses, such as serum concentrations and expression of inflammatory cytokines, phosphorylation of c-Jun N-terminal kinase (JNK) and IKKβ, and the accumulation of F4/80-positive macrophages in adipose tissue were also attenuated in Sirt1 knockout mice. The BBR-induced decrease in PGC-1α acetylation was reversed by inhibition or knockout of Sirt1 in adipocytes and adipose tissue. Together, these results indicate that adipose tissue SIRT1 is a key regulator of the insulin sensitizing and anti-inflammatory effects of BBR, which contributes to the improvement of metabolic dysregulation.
Highlights
Insulin resistance is a major factor involved in obesity-related clinical disorders, such as glucose intolerance, type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease (Moller and Kaufman, 2005)
We found that BBR reduced serum levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and inhibited activation of inhibitor of κB kinase beta (IKK-β), c-Jun N-terminal kinase (JNK), and proinflammatory M1 macrophages in the adipose tissue of high-fat diet (HFD)-induced obese mice, with concurrent improvements in glucose tolerance and insulin sensitivity (Shang et al, 2010; Ye et al, 2016)
We investigated whether the effect of BBR on glucose consumption and the adenosine monophosphate kinase (AMPK) pathway was dependent on SIRT1
Summary
Insulin resistance is a major factor involved in obesity-related clinical disorders, such as glucose intolerance, type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease (Moller and Kaufman, 2005). We found that BBR reduced serum levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and inhibited activation of inhibitor of κB kinase beta (IKK-β), c-Jun N-terminal kinase (JNK), and proinflammatory M1 macrophages in the adipose tissue of high-fat diet (HFD)-induced obese mice, with concurrent improvements in glucose tolerance and insulin sensitivity (Shang et al, 2010; Ye et al, 2016). It was previously reported that BBR treatment significantly downregulated the expression of proinflammatory genes, such as TNF-α, IL-1β, and IL-6 and monocyte chemoattractant protein-1 (MCP-1), in the adipose tissue of obese db/db mice and inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory genes, including IL-1β, IL-6, iNOS, and MCP-1, as well as proinflammatory signals in macrophages dependent on AMPK activation (Jeong et al, 2009). The direct mechanisms involved in BBR’s effects on AMPK and inflammation are not well understood
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