GBA3 promotes fatty acid oxidation and alleviates non-alcoholic fatty liver by increasing CPT2 transcription.

BACKGROUND: Excessive lipids accumulation and hepatocytes death are prominent characteristics of non-alcoholic fatty liver disease (NAFLD). Nonetheless, the precise pathophysiological mechanisms are not fully elucidated. METHODS: HepG2 cells stimulated with palmitic acids and rats fed with high-fat diet were used as models for NAFLD. The impact of Glucosylceramidase Beta 3 (GBA3) on fatty acid oxidation (FAO) was assessed using Seahorse metabolic analyzer. Lipid content was measured both in vitro and in vivo. To evaluate NAFLD progression, histological analysis was performed along with measurements of inflammatory factors and liver enzyme levels. Western blot and immunohistochemistry were employed to examine the activity levels of necroptosis. Flow cytometry and reactive oxygen species (ROS) staining were utilized to assess levels of oxidative stress. RESULTS: GBA3 promoted FAO and enhanced the mitochondrial membrane potential without affecting glycolysis. These reduced the lipid accumulation. Rats supplemented with GBA3 exhibited lower levels of inflammatory factors and liver enzymes, resulting in a slower progression of NAFLD. GBA3 overexpression reduced ROS and the ratio of cell apoptosis. Phosphorylation level was reduced in the essential mediator, MLKL, implicated in necroptosis. Mechanistically, as a transcriptional coactivator, GBA3 promoted the expression of Carnitine Palmitoyltransferase 2 (CPT2), which resulted in enhanced FAO. CONCLUSIONS: Increased FAO resulting from GBA3 reduced oxidative stress and the production of ROS, thereby inhibiting necroptosis and delaying the progression of NAFLD. Our research offers novel insights into the potential therapeutic applications of GBA3 and FAO in the management and treatment of NAFLD.

Correlation between insulin resistance and the rate of neutrophils-lymphocytes, monocytes-lymphocytes, platelets-lymphocytes in type 2 diabetic patients.

BACKGROUND: Insulin resistance (IR) was a prominent feature commonly observed in individuals with type 2 diabetes mellitus (T2DM). T2DM Individuals often exhibited a concomitant presence of low-grade chronic inflammation. In this study conducted retrospectively, the aim was to investigate the connection between neutrophils-lymphocytes rate (NLR), monocytes-lymphocytes rate (MLR), platelets-lymphocytes rate (PLR) and IR, specifically among individuals with T2DM. METHOD: This study encompassed a cohort of 405 individuals diagnosed with T2DM, comprising cases from January 2021 to November 2022. On the basis of whether there was IR or not, these sufferers were categorized into two cohorts, namely T2DM with IR group (292 cases) and T2DM without IR group (113 cases), as determined by a homeostasis model assessment-IR (HOMA-IR) value exceeding 2.0. RESULTS: The findings of this study demonstrated compelling evidence of distinct biomarker profiles between individuals with T2DM who had IR and those without IR. Specifically, the IR individuals displayed notably raise NLR, MLR, PLR, C reactive protein (CRP) and serum amyloid A (SAA). Additionally, there was a noticeable decrease in superoxide dismutase (SOD) levels. Furthermore, IR was negatively correlated with SOD values, while positive associations were found between IR and NLR, CRP, and SAA levels (p < 0.05). Moreover, a rise in NLR and PLR levels demonstrated an identical relationship with the prevalence of IR (p = 0.007, p = 0.025, separately). The Receiver operating characteristic (ROC) curve demonstrated that the areas under the curve (AUC) for NLR, MLR, PLR, CRP, SAA and SOD in predicting occurrence of IR in T2DM patients were 0.603, 0.575, 0.581, 0.644, 0.594 and 0.632 respectively, with sensitivity of 79.5%, 95.2%, 46.9%,54.1% (or 51.4), 47.6% (or 45.7%) and 98.6% and specificity of 37.2%, 19.5%, 69.9%, 69% (or 71.7%), 71.6% (or 73.5%) and 23% respectively. CONCLUSION: Our findings support the notion that higher magnitude of NLR, PLR, MLR, CRP, and SAA values, corresponded to lower SOD levels, indicating a more severe degree of IR in T2DM patients. Additionally, NLR, PLR, MLR, CRP, SAA, and SOD demonstrated predictive potential for assessing IR. Regrettably, due to the retrospective nature of this study, it was not feasible to take a measurement the majority of inflammatory factors and reactive oxygen species (ROS).

Cross-sectional association between prolactin levels and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: a retrospective analysis of patients from a single hospital in China.

OBJECTIVE: This study aimed to retrospectively assess the association between prolactin (PRL) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). DESIGN AND SETTING: A retrospective, cross-sectional study was conducted at a single hospital in Anhui, China. PARTICIPANTS: A total of 406 patients with T2DM (230 men and 176 women) was included. OUTCOME MEASURES: P values for the independent t-test, the Mann-Whitney rank-sum test, the Spearman correlation analysis and multiple logistic regression models were used to explore the association between PRL and NAFLD in patients with T2DM. RESULTS: The results indicated that in both men and women, the levels of PRL were significantly lower in the T2DM with NAFLD group than in the T2DM without NAFLD group (men: 9.56 ng/mL vs 10.36 ng/mL, women: 10.38 ng/mL vs 12.97 ng/mL). In male patients, the levels of PRL were negatively correlated with hip circumference (r=-0.141, p=0.032), homoeostasis model assessment for insulin resistance (C-peptide) (r=-0.141, p=0.032) and triglyceride (TG) (r=-0.252, p=0.000) values and inversely correlated with high-density lipoprotein (r=0.147, p=0.025) levels. In female patients, PRL levels were negatively related to body mass index (r=-0.192, p=0.011), diastolic blood pressure (r=-0.220, p=0.003), waist circumference (r=-0.152, p=0.044), hip circumference (r=-0.157, p=0.037) and TG (r=-0.258, p=0.001) values. Logistic regression analysis revealed a negative relationship between PRL and NAFLD (men: OR 0.891, 95% CI 0.803 to 0.989, p=0.031; women: OR 0.874, 95% CI 0.797 to 0.957, p=0.004). As PRL levels increased, NAFLD prevalence decreased in both sexes (men: p=0.012, women: p=0.013). CONCLUSION: Our results suggest that low levels of PRL in the physiological range were markers of NAFLD in patients with T2DM and that PRL within the biologically high range may play a protective role in the pathogenesis of NAFLD.

Correlation between the thyroid hormone levels and nonalcoholic fatty liver disease in type 2 diabetic patients with normal thyroid function.

BACKGROUND: The objective of this study is to retrospectively analyze the correlation between the thyroid hormones and nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients with normal thyroid function. METHODS: Totally 586 T2DM patients with normal thyroid function participated in this research and were divided into T2DM without NAFLD (240 cases) group and T2DM with NAFLD (346 cases) group. The NAFLD fibrosis score (NFS) > 0.676 was defined as progressive liver fibrosis and used to categorize the patients into T2DM without progressive liver fibrosis group (493 cases) and T2DM with progressive liver fibrosis group (93 cases). RESULTS: The results indicated that the levels of free triiodothyronine (FT3), total triiodomethylamine (TT3) and FT3/free thyroxine ratio (FT3/FT4) were significantly higher while the FT4 level was lower in T2DM with NAFLD group than that in T2DM without NAFLD group (p < 0.05). The levels of FT3, FT4, TT3 and TT4 in patients with progressive liver fibrosis were significantly lower in patients with progressive liver fibrosis than that in patients without progressive liver fibrosis (p < 0.05). Logistic regression analysis showed a positive connection between FT3/FT4 ratio and NAFLD (p = 0.038), a negative relationship between FT4 level and NAFLD (p = 0.026), between the levels of FT4, TT3 and total thyroxine (TT4) and the risk of progressive hepatic fibrosis (p = 0.022, p = 0.007, p = 0.046). CONCLUSION: There is a certain correlation between thyroid hormone levels and NAFLD in T2DM patients, suggesting that the assessment of thyroid hormone levels in T2DM patients with normal thyroid function could be helpful in the prevention and treatment of NAFLD.

Correlational study on the levels of 25-hydroxyvitamin D and non-alcoholic fatty liver disease in type 2 diabetic patients.

BACKGROUND: It is widely acknowledged that nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus(T2DM) are all chronic metabolic diseases. The objective of this study is to retrospectively probe the association between the 25-hydroxyvitamin D (25-(OH)D) and NAFLD in type 2 diabetic patients. METHODS: Three hundred thirty-nine T2DM patients participated in this research and from November 2018 to September 2019 and were divided into simple T2DM group (108 cases) and T2DM with NAFLD group (231 cases) in conformity with abdominal ultrasound diagnosis. The NAFLD fibrosis score (NFS) ≥0.676 was defined as progressive liver fibrosis.231 T2DM with NAFLD patients were categorized into two subgroups: progressive liver fibrosis subgroup (48 cases) and without progressive liver fibrosis subgroup (183 cases). RESULTS: The prevalence of NAFLD by Abdominal ultrasonography was 68%.The results indicated that the levels of 25-(OH) D were significantly lower in T2DM with NAFLD group than that in simple T2DM group(P < 0.01). The levels of 25-(OH) D were significantly lower in progressive liver fibrosis subgroup than that in patients without progressive liver fibrosis and simple T2DM,and 25-(OH) D levels were lower in without progressive liver fibrosis subgroup than that in simple T2DM group(p < 0.01 or p < 0.05). Multivariate logistic regression analysis showed that levels of 25-(OH) D were negative correlation with risk of NAFLD and progressive liver fibrosis(p = 0.011、p = 0.044,respectively). CONCLUSIONS: we could come to a conclusion that low levels of 25-(OH) D was a risk factor for NAFLD and progressive liver fibrosis in T2DM patients.

Overweight, obesity and endometrial cancer risk: results from a systematic review and meta-analysis.

AIM: Findings from recent studies suggest that obesity may be associated with an increased risk of endometrial cancer, but several earlier studies were less conclusive. Here we strive to estimate this relationship in a meta-analysis of published data. METHODS: We searched Pubmed and Embase for studies on body mass index and the risk of endometrial cancer, published from 1989 to 2011. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending on the degree of heterogeneity. RESULTS: Seven cohort studies and 11 case-control studies were included in the meta-analysis. Overall, the conditions of excess body weight ([EBW] defined as body mass index [BMI] ≥25 kg/m²), obesity (BMI ≥30 kg/m²) and overweight (25< BMI <30 kg/m²) were associated with an increased risk of endometrial cancer (relative risk [RR] for EBW=1.62, 95% confidence interval [CI], 1.39-1.89; for obesity RR=2.54, 95% CI, 2.11-3.06; for overweight RR=1.32, 95% CI, 1.16-1.50). Subgroup analyses showed that the positive associations were independent of study design, geographic locations, self-reported BMI, alcohol use, smoking habit, history of diabetes, hormone therapy, age at menarche, age at menopause, parity, and age at first full term pregnancy. However, there was no statistically significant association between EBW and endometrial cancer risk for measured BMI (for EBW RR=1.29, 95% CI, 0.66-2.53). CONCLUSIONS: The findings from this meta-analysis strongly support that the conditions of EBW, overweight, and obesity are all associated with an increased risk of endometrial cancer. Also, the strength of the association increases with increasing BMI.