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Background: We recently demonstrated a positive effect of berberine on nonalcoholic fatty liver disease patients after 16 weeks of treatment by comparing mere lifestyle intervention in type 2 diabetes patients with berberine treatment, which decreased the content of hepatic fat. However, the potential mechanisms of the clinical effects are unclear. We used a lipidomic approach to characterize the state of lipid metabolism as reflected in the circulation of subjects with nonalcoholic fatty liver disease (NAFLD) before and after berberine treatment.Methods: Liquid chromatography-mass spectrometry evaluated the various lipid metabolites in serum samples obtained from the participants (41 patients in the berberine group and 39 patients in the mere lifestyle intervention group) before and after treatment.Results: A total of 256 serum lipid molecular species were identified and quantified. Both treatments regulated various types of lipids in metabolic pathways, such as free fatty acids, phosphoglycerides and glycerides, in metabolic pathways, but berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment. Berberine also caused obvious differences on ceramides. Berberine treatment markedly decreased serum levels of ceramide and ceramide-1-phosphate.Conclusions: Berberine altered circulating ceramides, which may underlie the improvement in fatty liver disease. ClinicalTrials.gov NCT00633282, Registered March 3, 2008. [ABSTRACT FROM AUTHOR]

Background: We recently demonstrated a positive effect of berberine on nonalcoholic fatty liver disease patients after 16 weeks of treatment by comparing mere lifestyle intervention in type 2 diabetes patients with berberine treatment, which decreased the content of hepatic fat. However, the potential mechanisms of the clinical effects are unclear. We used a lipidomic approach to characterize the state of lipid metabolism as reflected in the circulation of subjects with nonalcoholic fatty liver disease (NAFLD) before and after berberine treatment., Methods: Liquid chromatography-mass spectrometry evaluated the various lipid metabolites in serum samples obtained from the participants (41 patients in the berberine group and 39 patients in the mere lifestyle intervention group) before and after treatment., Results: A total of 256 serum lipid molecular species were identified and quantified. Both treatments regulated various types of lipids in metabolic pathways, such as free fatty acids, phosphoglycerides and glycerides, in metabolic pathways, but berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment. Berberine also caused obvious differences on ceramides. Berberine treatment markedly decreased serum levels of ceramide and ceramide-1-phosphate., Conclusions: Berberine altered circulating ceramides, which may underlie the improvement in fatty liver disease. ClinicalTrials.gov NCT00633282, Registered March 3, 2008.

Background: The association between serum Retinol Binding Protein 4 (RBP4) and obesity is still controversial. Serum RBP4 levels varies by gender, and estradiol may play a role in the difference. To investigate the participation of sex hormones in the association of RBP4 and obesity in humans, we measured serum RBP4, BMI, and sex hormones in 87 women from the outpatient., Methods: Eighty-seven subjects of Chinese women origin from the outpatient (aged 40.22 ± 15.54 years) were enrolled. Subjects with diseases affecting the metabolic state or not suitable to participate in this study were excluded. Anthropometrics and laboratory tests, including lipid profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), estradiol (E2),progesterone (PROG), testosterone (TESTO), and dehydroepiandrosterone (DHEA) were conducted. Serum RBP4 was detected by an enzyme immunoassay kit and validated by quantitative Western blotting., Results: Circulating RBP4 levels were positively associated with BMI, waist circumference, waist-to-hip ratio (WHR), systolic and diastolic (SBP), diastolic blood pressure (DBP), triglycerides (TG), low high-density lipoprotein cholesterol(LDL-c), and testosterone (TESTO) in the total group. While only in obese individuals, serum RBP4 levels were negatively associated with E2. The highest value was in the subjects with both obesity and the low estrogen level. Multiple linear regression analysis revealed that RBP4 correlated independently with TG, TC and insulin in all subjects, TC in non- obese individuals. However, E2 were significantly associated with serum RBP4 only in obese individuals., Conclusions: RBP4 could be a marker of obesity-related factors; estrogen was negatively related to RBP4 and might be one of the influential factors.

Background: High serum Retinol Binding Protein 4 (RBP4) levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured serum RBP4 and hepatic fat content (HFC), visceral (VFA) and subcutaneous abdominal fat area (SFA) in 106 subjects with non-alcoholic fatty liver disease (NAFLD) without known diabetes., Methods: 106 patients with NAFLD (M/F: 61/45, aged 47.44±14.16 years) were enrolled. Subjects with known diabetes, chronic virus hepatitis, and those with alcohol consumption≥30 g/d in man and ≥20 g/d in woman were excluded. Anthropometrics and laboratory tests, including lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (γ-GT) were conducted. HFC, VFA and SFA were determined by CT scan. Serum RBP4 was detected by an enzyme immunoassay kit and validated by quantitative Western blotting., Results: Circulating RBP4 was negatively associated with high-density lipoprotein cholesterol (HDL-c) (r=-0.392, p<0.001), but positively with waist-to-hip ratio (WHR) (r=0.343, p=0.001), triglyceride (r=0.330, p=0.002), VFA (r=0.298, p=0.027), systolic blood pressure (r=0.247, p=0.020), diastolic blood pressure (r=0.241, p=0.023), γ-GT (r=0.239, p=0.034), waist circumference (r=0.218, p=0.040). Differently, serum RBP4 levels were not associated with HFC (r=0.199, p=0.071), SFA, age, BMI, total cholesterol, low-density lipoprotein cholesterol (LDL-c), ALT or AST (all p>0.05). Multiple linear regression analysis revealed that RBP4 correlated independently with VFA (Standard β=0.357, p=0.019) and HDL-c (Standard β=-0.345, p=0.023) in all subjects, HDL-c (Standard β=-0.315, p=0.040) in men, VFA/SFA in women (Standard β=0.471, p=0.049), not with HFC. However, serum RBP4 was positively correlated with HFC when HFC below 6.34% (r=0.574, p=0.001)., Conclusions: RBP4 could be a marker of abdominal obesity, however, the role of RBP4 in the pathogenesis of NAFLD is not sufficiently elucidated.

Background: To observe the relationship between serum retinol binding protein 4(RBP4) and β cell function in Chinese subjects with non-alcoholic fatty liver disease (NAFLD) and without known diabetes., Methods: 106 patients diagnosed as fatty liver by ultrasonography (M/F: 61/45; aged 47.44 ± 14.16 years) were enrolled in our current cross-sectional study. Subjects with known diabetes, chronic virus hepatitis and excessive alcohol consumption were excluded. Serum RBP4 was detected by ELISA and validated by quantitative Western blotting. β cell function were assessed by HOMA in all subjects and by hyperglycemic clamp in 17 normal glucose tolerance subjects (M = 6, F = 11)., Results: The levels of serum RBP4 in men were higher than that in women (55.96 ± 11.14 vs 45.87 ± 10.31 μg/ml, p < 0.001). Pearson's correlation analysis demonstrated that in women, serum RBP4 levels were significantly associated with fasting blood glucose (FBG), HOMA-β, and increment of first phase insulin secretion (1PH), but not associated with age, BMI, waist circumference, WHR, systolic (SBP) and diastolic blood pressure (DBP), TC, TG, HDL-c, LDL-c, 2 h blood glucose, HOMA-IR, ALT, AST, γ-GT, hepatic fat content (HFC), and insulin sensitivity index (ISI). However, in men, serum RBP4 levels were significantly associated with HDL-c, ALT, AST, but not associated with any other parameters as mentioned above. A stepwise multiple linear regression analysis demonstrated that in women, HOMA-IR and RBP4 were significantly associated with HOMA-β, while in men, HOMA-IR and BMI were significantly variables associated with HOMA-β., Conclusions: Serum RBP4, secreted mainly by liver and adipose tissue, may involve in the pathogenesis of β cell dysfunction in Chinese women patients with NAFLD.