Lifang Ye1, Shu Liang2, Chao Guo2, Xizhong Yu2, Juan Zhao2, Hao Zhang2, Wenbin Shang3. 1. Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Endocrinology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. 2. Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China. 3. Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Endocrinology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: wbshang@njucm.edu.cn.
Abstract
AIMS: Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue. MAIN METHODS: High-fat-diet induced obese mice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined. KEY FINDINGS: Berberine significantly decreased F4/80+/CD11c+/CD206- cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages. SIGNIFICANCE: Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue.
AIMS: Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue. MAIN METHODS: High-fat-diet induced obesemice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined. KEY FINDINGS:Berberine significantly decreased F4/80+/CD11c+/CD206- cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages. SIGNIFICANCE: Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue.
Authors: Robyn Bruen; Sean Curley; Sarina Kajani; Daniel Crean; Marcella E O'Reilly; Margaret B Lucitt; Catherine G Godson; Fiona C McGillicuddy; Orina Belton Journal: Cardiovasc Diabetol Date: 2017-11-06 Impact factor: 9.951
Authors: Hsin Hsueh Shen; Stephen J Peterson; Lars Bellner; Abu Choudhary; Lior Levy; Leah Gancz; Ariel Sasson; Joseph Trainer; Rita Rezzani; Abraham Resnick; David E Stec; Nader G Abraham Journal: Antioxidants (Basel) Date: 2020-06-04