Visceral adipose dysfunction is a major cause of metabolic disorders. However, there is lack of a clinical index for prediction of visceral fat dysfunction in Asians. The present study aims to establish a visceral adiposity index for evaluation of metabolic health status in Chinese, the largest Asian ethnic group. 485 subjects were recruited from Lianqian Community, Xiamen and received abdominal computed tomography(CT) for visceral fat area. A Chinese visceral adiposity index (CVAI) was created using multivariate linear regression analyses, and was further validated in 6495 subjects recruited from Changfeng Community, Shanghai. CVAI was well associated with visceral obesity (r = 0.68, P < 0.001) and HOMA-IR (r = 0.60, P < 0.001). The AUROCs were 0.89(0.88–0.90), 0.72(0.71–0.73), 0.69(0.68–0.71) and 0.67(0.65–0.68) for determination of metabolic syndrome, hypertension, diabetes and prediabetes, respectively. CVAI was more valuable compared to BMI and waist circumference in evaluation of metabolic risks (all P < 0.001), even in subjects with metabolically unhealthy normal weight (MUNW) and metabolically healthy obese/overweight (MHO). This study demonstrates that CVAI is a reliable and applicable index for evaluation of visceral fat dysfunction in Chinese. It might be used to evaluate metabolic health status in Asians.

A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD. A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR. As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression. BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism. ClinicalTrials.gov NCT00633282

Accurate measures of liver fat content are essential for investigating the role of hepatic steatosis in the pathophysiology of multiple metabolic disorders. No traditional imaging methods can accurately quantify liver fat content. [¹H]‐magnetic resonance spectroscopy (MRS) is restricted in large‐scale studies because of the practical and technological issues. Previous attempts on computer‐aided ultrasound quantification of liver fat content varied in method, and the ultrasound quantitative parameters measured from different ultrasound machines were hardly comparable. We aimed to establish and validate a simple and propagable method for quantitative assessment of liver fat content based on the combination of standardized ultrasound quantitative parameters, using [¹H]‐MRS as gold standard. Totally 127 participants were examined with both ultrasonography (US) and [¹H]‐MRS. Ultrasound hepatic/renal echo‐intensity ratio (H/R) and ultrasound hepatic echo‐intensity attenuation rate (HA) were obtained from ordinary ultrasound images using computer program. Both parameters were standardized using a tissue‐mimicking phantom before analysis. Standardized ultrasound H/R and HA were positively correlated with the liver fat content by [¹H]‐MRS (r = 0.884, P < 0.001 and r = 0.711, P < 0.001, respectively). Linear regression analysis showed ultrasound H/R could modestly predict the amount of liver fat (adjusted explained variance 78.0%, P < 0.001). The addition of ultrasound HA slightly improved the adjusted explained variance to 79.8%. Difference of estimated liver fat contents between different ultrasound machines and operators was reasonably well. Thus, computer‐aided US is a valid method to estimate liver fat content and can be applied extensively after standardization of ultrasound quantitative parameters.

Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berberine (BBR), a natural compound, is commonly used as a nonprescription drug to treat diarrhea. Here, we reported that 1-month BBR intervention increased BAT mass and activity, reduced body weight, and improved insulin sensitivity in mildly overweight patients with non-alcoholic fatty liver disease. Chronic BBR treatment promoted BAT development by stimulating the expression of brown adipogenic genes, enhanced BAT thermogenesis, and global energy expenditure in diet-induced obese mice and chow-fed lean mice, Consistently, BBR facilitated brown adipocyte differentiation in both mouse and human primary brown preadipocytes. We further found that BBR increased the transcription of PRDM16, a master regulator of brown/beige adipogenesis, by inducing the active DNA demethylation of PRDM16 promoter, which might be driven by the activation of AMPK and production of its downstream tricarboxylic acid cycle intermediate α-Ketoglutarate. Moreover, chronic BBR administration had no impact on the BAT thermogenesis in adipose-specific AMPKa1 and AMPKa2 knockout mice. In summary, we found that BBR intervention promoted recruitment and activation of BAT and AMPK–PRDM16 axis was indispensable for the pro-BAT and pro-energy expenditure properties of BBR. Our findings suggest that BBR may be a promising drug for obesity and related metabolic disorders in humans partially through activating BAT.