Huanglian-Jiedu decoction promotes adipose thermogenesis in obese mice by suppressing the expression of HDAC3.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is an ancient formula of traditional Chinese medicine that is commonly utilized in a range of disorders, and it has been shown to have pharmacological effects on glucose and lipid metabolism. However, the specific mechanism of HLJDD for the treatment of obesity and related metabolic disorders remains to be further investigated. AIM OF THE STUDY: It has been thought that encouraging adipose thermogenesis to raise the body's energy expenditure is a useful tactic for improving metabolic abnormalities and losing weight. In this study, we investigated the ability and underlying mechanisms of HLJDD to regulate fat cell thermogenesis to improve energy expenditure in obesity. METHODS: The obese mouse model was established on a high-fat diet for 12 weeks. All mice were divided into NC, HFD, HFD with HLJDD of a low dose (2.25 g/kg/d), and HFD with HLJDD of a high dose (4.5 g/kg/d) groups and kept for 4 weeks. In vitro experiments were conducted to evaluate the effects of 5% and 10% HLJDD-containing serum on differentiated 3T3-L1 cells and HDAC3-knocking-down 3T3-L1 cells. RESULTS: The results showed that HLJDD treatment significantly improved glucose and insulin tolerance and decreased the adipocyte radius of WATs, as well as increased energy consumption in obese mice. Besides, HLJDD treatment dramatically increased the levels of thermogenic genes UCP-1 and PGC-1α while suppressing HDAC3 levels in WATs and 3T3-L1 adipocytes. Importantly, the effects of HLJDD on PGC-1α and UCP-1 were blocked in HDAC3 knockdown adipocytes. CONCLUSIONS: Therefore, these results suggest that HLJDD enhanced adipose thermogenesis and improved energy expenditure by inhibiting HDAC3, thereby increasing UCP-1 and PGC-1α expression. These findings amplified the mechanisms of HLJDD and its potential to treat obesity and related metabolic disorders.

Rhein targets macrophage SIRT2 to promote adipose tissue thermogenesis in obesity in mice.

Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

Efficacy and safety of diacerein monotherapy in adults with obesity: A randomized, double-blind, placebo-controlled trial.

AIM: To assess the efficacy and safety of diacerein monotherapy in adults with obesity. METHODS: Forty-two adults with obesity participated in the study and were randomly assigned to receive diacerein or placebo in addition to lifestyle modification for 14 weeks, in a double-blinded fashion. Differences in changes in body weight, body composition, metabolic variables, fatty liver-related indicators, cardiovascular system variables, lifestyle score and metabolic factors were compared. RESULTS: Post-treatment weight loss percentage from baseline was -6.56% (-8.71%, -4.41%) in the diacerein group and -0.59% (-2.74%, 1.56%) in the placebo group. Compared with the placebo group, the diacerein group showed significant improvements in body composition, metabolic variables and indicators related to fatty liver. In addition, after 14 weeks of treatment, diacerein led to a significant reduction in serum visfatin concentration versus the placebo group. The reductions in total body fat mass and visceral fat area mediated the weight loss induced by diacerein. No significant differences were found between the groups in the number of adverse events and safety variables. CONCLUSIONS: For adults with obesity, diacerein led to a clinically meaningful weight loss and provided multiple metabolic benefits with acceptable safety. These results support that diacerein is a promising candidate medicine to be developed for obesity management.

VEGF-B is involved in diabetic peripheral neuropathy in patients with type 2 diabetes.

Aims: This study aims to explore the potential role of vascular endothelial growth factor-B (VEGF-B) in the pathogenesis of diabetic peripheral neuropathy (DPN). The expression of VEGFRs were reanalysed by using gene arrays of peripheral nerve samples from mouse models of DPN retrieved from the GEO database. 213 T2D patients as well as 31 healthy individuals were recruited. The serum VEGF-B was detected and its relationship with DPN was analysed. The elevated VEGFR1 was the only change of VEGFR gene expression in the peripheral nerve from mouse models of DPN. The level of serum VEGF-B in T2D patients with DPN was higher than that in T2D patients without DPN and healthy people. Analysis of correlation and binary logistic regression confirmed that the increased serum VEGF-B level was an independent risk factor of DPN in T2D patients. VEGF-B-VEGFR1 signaling pathway may be involved in the development of DPN.

Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017-2020.

Background: Hepatic steatosis is a significant pathological feature of fatty liver disease (FLD) which is widely spread with no effective treatment available. Previous studies suggest that chromium (Cr) intake reduces lipid deposition in the liver in animals. However, the connection between blood Cr and hepatic steatosis among humans remains inconclusive. Methods: Using the data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, we performed a cross-sectional analysis, including 4,926 participants. The controlled attenuation parameter (CAP) measured by the vibration controlled transient elastography (VCTE) was used to evaluate the degree of liver steatosis. Weighted univariate regression, multivariate linear regression, smooth fitting curves and subgroup analysis were used. In addition, we carried out trend tests, multiple interpolations, and interaction analyses to conduct sensitivity analyses. Results: After adjusting with various covariables, multivariate linear regression analysis demonstrated a significant negative correlation between blood Cr and CAP [ß (95% CI) = -5.62 (-11.02, -0.21)]. The negative correlation between blood Cr and CAP was more significant in the males, 50-59 years, overweight, hypercholesterolemia, HDL-C ≥ 65 mg/dL, HbA1c (5.70-6.10 %), HOMA-IR (0.12-2.76), total bilirubin (0.30-0.40 mg/dL), ever alcohol consumption subjects. Of note, the relationships between blood Cr and CAP followed a U-shaped curve in the smokers and non-smokers, with blood Cr thresholds of 0.48, 0.69 µg/L, respectively. Conclusions: There is an independently negative correlation between blood Cr and hepatic steatosis in American. Our study provides clinical researchers with a new insight into the prospective prevention of hepatic steatosis.

Seroprevalence and Risk Factors of Toxoplasma gondii Infection of Cattle and Goats in Farms of Hunan Province, China.

Background: Toxoplasmosis is one of the most widespread foodborne parasitic zoonoses caused by the obligate intracellular protozoan Toxoplasma gondii. Although a number of studies have reported on the seroprevalence and risk factors of T. gondii infection in ruminants in China, information about T. gondii infection in cattle in Hunan province of China is not available. Material and Methods: Sera of 985 cattle and 1147 goats were examined for the presence of specific antibodies against T. gondii using the indirect hemagglutination test. Some risk factors related to the presence of cats, herd size, gender, age, and geographical origin were determined using a binary logistic regression. Results: Specific IgG against T. gondii were detected in 8.3% (82/985) and 13.3% (153/1147) of the cattle and goats, respectively. Based on statistical analysis, the presence of cats and gender were considered important risk factors for T. gondii infection in cattle and goats in the farms in this study (P < 0.05). Conclusion: Our results provide a baseline for future prevention and control of T. gondii infection in cattle and goats in Hunan province, subtropical China. This is the first report of T. gondii seroprevalence in cattle in Hunan province, China.

Acetylation of p65Lys310 by p300 in macrophages mediates anti-inflammatory property of berberine.

Nuclear factor (NF)-κB plays a pivotal role in the regulation of inflammatory response in macrophages. Berberine (BBR), which is an active constituent isolated from Coptis rhizome, possesses a prominent anti-inflammatory activity. Here we show that BBR changes the global acetylation landscape in LPS-induced protein acetylation of macrophages and reduces the acetylation of NF-κB subunit p65 at site Lys310(p65Lys310), leading to the inhibition of NF-κB translocation and transcriptional activity to suppress the expressions of inflammatory factors. BBR resists the inflammatory response in acute LPS-stimulated mice through downregulation of p65Lys310 acetylation in peritoneal macrophages. In obese mice, BBR alleviates the metabolic disorder and inflammation with the reduced acetylation of p65Lys310 in white adipose tissue. Furthermore, we demonstrate that BBR acts as a regulator of p65Lys310 by inhibiting the expression of p300 in macrophages. Our findings elucidate a new molecular mechanism for the anti-inflammatory effect of BBR via the p300/p65Lys310 axis.

Upregulation of adiponectin by Ginsenoside Rb1 contributes to amelioration of hepatic steatosis induced by high fat diet.

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.

Increased Serum VEGF-B Level Is Associated With Renal Function Impairment in Patients With Type 2 Diabetes.

Aims/Introduction: Renal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients. Materials and Methods: Serum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR<90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR. Results: Serum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR<90 mL/min/1.73m2. Conclusions: Serum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease.