BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

【Objective】 To observe the therapeutic effects of Axitinib, a tyrosine kinase receptor inhibitor, on liver fibrosis. 【Methods】 In vivo, CCL4 was injected intraperitoneally to induce liver fibrosis in mice. After modeling, Axitinib-carboxymethyl cellulose (Axitinib-CMC) solution or CMC solution were administered by gavage. After 2 weeks of modeling, 4 weeks of modeling, 1 week of treatment and 2 weeks of treatment, the mice were killed and their liver tissues were stained by HE, Masson and α - SMA immunohistochemistry. In vitro, human hepatic stellate cell line (LX2) and human normal liver cell line (LO2) were intervened with different concentrations of Axitinib-CMC solution. MTT assay was performed 48 h and 72 h after the intervention. Flow cytometry was used to observe the apoptosis of the two cell lines. Western blotting was used to detect the expressions of Fas, Caspase-8, Caspase-3 and Bcl-2 proteins. 【Results】 HE and Masson staining results showed that CCL4 could induce liver fibrosis in the mice, and the degree of liver fibrosis was more severe in the 4-week than that in the 2-week treatment group. After treatment with Axitinib, the collagen staining area and the positive expression level of α-SMA were significantly lower than those in 4-week group and CMC treatment control group (P<0.05). In vitro, Axitinib could effectively inhibit the viability of hepatic stellate cell line LX2 and promote its apoptosis. Meanwhile, the expressions of pro-apoptotic proteins Fas, Caspase-8 and Caspase-3 increased, while the expression of apoptosis suppressor gene Bcl-2 decreased. However, the above changes were not found in control hepatocyte line LO2. 【Conclusion】 Axitinib exerts an anti-fibrosis effect by inducing apoptosis of hepatic stellate cells, and has no significant effect on normal hepatocytes.

OBJECTIVECellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.

METHODSThe inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.

RESULTSCisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.

CONCLUSIONOur results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.

Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cellular Senescence ; Cisplatin ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p19 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Hep G2 Cells ; Humans ; Tumor Suppressor Protein p53 ; metabolism ; Up-Regulation

Objective Cellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin. Methods The inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associatedβ-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting. Results Cisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells. Conclusion Our results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.

Objective Cellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin. Methods The inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associatedβ-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting. Results Cisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells. Conclusion Our results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.