Diabetology & Metabolic Syndrome

Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Epigallocatechin-3-gallate (EGCG) derived from extract of green tea and is well known for beneficial effects on anti-oxidative, anti-inflammatory, and anti-tumor activity. The present study aimed to implore its underlying mechanism for protective effect of NAFLD. Mice were fed either high fat diet (HFD) or chow diet with or without EGCG treatment in HFD group, for up to 16 weeks. Histopathology, expression of lipid and glucose metabolism and lipogenesis-related gene expression were assessed. Primary mouse hepatocytes were treated with free fatty acids combined with different doses of EGCG for 48 h, expression of lipid and lipogenesis-related gene expression were assessed. The results showed that EGCG attenuated HFD- and FFA-induced lipid accumulation in vivo and in vitro. EGCG can decrease the oxidative stress and promote Nrf2 level. Meanwhile EGCG alleviated FGF21 resistance and elevated FGFR/AMPK expression, which suggested an unrecognized mechanism of EGCG in ameliorating NAFLD. EGCG attenuated hepatocytes damage and dysfunction in NAFLD by alleviating FGF21 resistance and improve FGFR/AMPK pathway, mitigating oxidative stress. Our studies verified that EGCG may become a promising drug to treat or relieve NAFLD.

The nutrition transition in developing countries like Iran causes the increasing rise of obesity and abdominal obesity rates. However, it is not yet well proven that environmental modifications like improving the quality of beverage intake can be effective in people who have a genetic predisposition to obesity. So, in the present study, we examine the interaction between genetic predisposition and healthy beverage index (HBI) with abdominal obesity and obesity-related metabolic risk factors in overweight and obese women. Based on inclusion and exclusion criteria, 202 overweight or obese females were chosen for this cross-sectional study. Body composition, anthropometric measures, physical activity, and beverage intake data were collected and analyzed using recognized and trustworthy methodologies. Biochemical tests were performed on serum samples. A genetic risk score (GRS) was calculated based on the results of genetic tests. The predetermined HBI was calculated based on previous studies. A generalized linear model was used to estimate the interactions between GRS and HBI (GLM). We found significant interactions between GRS and HBI on WHR (β = − 0.39, CI: -0.07 to 0.001, P = 0.05) and WC (β = − 6.18, CI: − 13.41 to 1.05, P = 0.09). Also, there were significant gene-diet interactions for HBI and GRS on HDL (β = 7.09, CI: − 0.73 to 14.92, P = 0.07) and FBS (β = − 9.07, CI: − 18.63 to 0.47, P = 0.06). These findings emphasize the HBI considering genetics appears to protect against the risks of abdominal obesity and metabolic associated obesity markers.

Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the β-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target β-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. Seven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation. Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic–euglycemic clamp relative to the baseline. Other measures of β-cell indices like HOMA-β, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory. ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict β-cell function in patients with advanced duration of T2DM. Trial registration -Clinicaltrials.gov NCT01759823

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Histone lysine-specific demethylase 1 (LSD1) is a flavin-containing amino oxidase that can repress or activate transcription. The aim of this study is to explore the mechanism of LSD1 aggravating DN-induced renal fibrosis. The STZ-induced DN rat model was established for in vivo study. The rats were divided into four groups: Sham, STZ, STZ + Ad-shNC and Ad-shLSD1. The Hematoxylin–eosin (HE) staining was used to evaluate the renal injury. The Immunofluorescence assay was used to determine the LSD1, Fibronectin and α-SMA expression. The related protein expression was detected by western blot. Knockdown of LSD1 alleviated STZ-induced renal injury. Moreover, knockdown of LSD1 decreased the expression of serum biochemical markers, containing urine output (24 h), urinary protein (24 h), serum creatinine, BUN and UACR. Furthermore, we proved that knockdown of LSD1 alleviated renal fibrosis in STZ-induced DN rats. In vitro, knockdown of LSD1 suppressed NRK-49F cells activation and overexpression of LSD1 induced renal fibrosis. In addition, knockdown of LSD1 could deactivate TGF-β1/Smad3 pathway and promote sirtuin 3 (SIRT3) expression in vivo and in vitro. The rescue experiments confirmed that LSD1 induced renal fibrosis via decreasing SIRT3 expression and activating TGF-β1/Smad3 pathway. LSD1 deficiency leads to alleviate STZ-induced renal injury and overexpression of LSD1 induces renal fibrosis via decreasing SIRT3 expression and activating TGF-β1/Smad3 pathway, which provides a reasonable strategy for developing novel drugs targeting LDS1 to block renal fibrosis.