Probiotics-rich emulsion improves insulin signalling in Palmitate/Oleate-challenged human hepatocarcinoma cells through the modulation of Fetuin-A/TLR4-JNK-NF-κB pathway.

BACKGROUND: Fetuin-A, also known as α2-Heremans-Schmid glycoprotein (AHSG), is an abundant plasmatic serum protein synthesized predominantly in liver and adipose tissue. This glycoprotein is known to negatively regulate insulin signaling through the inhibition of insulin receptor (IR) autophosphorylation and tyrosine kinase activity, which participates in insulin resistance (IR) and metabolic syndrome development. Recent studies demonstrated that IR and associated metabolic disorders, are closely related to the gut microbiota and modulating it by probiotics could be effective in metabolic diseases management. OBJECTIVE: In this present work we aimed to evaluate the effects of a probiotics-rich emulsion on reducing the IR induced by free fatty acids accumulation in human hepatocarcinoma cell line, and to elucidate the implicated molecular pathways, with a specific emphasis on the hepatokin Fetuin-A-related axis. RESULTS: Here we showed, that probiotics improve HepG2 viability, protect against apoptosis under normal and IR conditions. Moreover, the emulsion was successful in attenuating oxidative stress as well as improving mitochondrial metabolism and dynamics. Interestingly, application of the probiotics to lipotoxic HepG2 cells resulted in significant reduction of Fetuin-A/TLR4/JNK/NF-κB pathway activation, which suggests a protective effect against inflammation, obesity as well as liver related insulin resistant. CONCLUSION: Overall, the presented data reports clearly on the potent potential of probiotics formulated in an emulsion vehicle to enhance metabolic functions of affected IR HepG2 cells, and suggest the possibility of using such preparations as insulin sensitizing therapy, playing at the same time protective role for the development of liver related insulin resistant.

Effect of liraglutide therapy on serum fetuin A in patients with type 2 diabetes and non-alcoholic fatty liver disease.

OBJECTIVE: We aimed to compare the effectiveness of liraglutide vs. pioglitazone on hepatic fat content and serum fetuin A levels in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. METHODS: This was a single-center, open-label, prospective, and randomized trial using a parallel design and lasting 24 weeks. Sixty patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease were randomly assigned to the liraglutide and pioglitazone groups on a 1:1 basis using a computer-generated sequence. Fetuin-A levels were determined using enzyme-linked immunosorbent assay. Hepatic fat content was measured using proton 1H-MRS on a 1.5T whole-body MRI scanner. All analyses were performed with SPSS version 13.0. RESULTS: In the liraglutide group, fetuin-A levels decreased after 24 weeks (666.1±109.4 vs. 443.7±90.5µg/mL, P<0.05). In the pioglitazone group, fetuin-A levels also decreased after 24 weeks (659.3±111.8 vs. 538.1± 101.0µg/mL, P<0.05) but not to the level of the liraglutide group. The liraglutide treatment resulted in a decrease in 1H-MRS (24.1±3.0 vs. 20.1±3.8, P<0.05). After 24 weeks, ΔFetuin-A was positively correlated with Δweight (r=0.756, P=0.035), ΔBMI (r=0.653, P=0.006), Δwaist circumference (r=0.767, P=0.010), and Δ1H-MRS (r=0.732, P=0.004) in the liraglutide group. CONCLUSIONS: Liraglutide treatment resulted in a decrease in hepatic fat content and fetuin-A compared with pioglitazone treatment in patients with T2DM and NAFLD. Fetuin-A is positively correlated with weight and hepatic fat content. The reduction in the hepatic fat content may be attributed to weight loss rather than reduction of glucose.

Lowering effect of valsartan on fetuin-A in type 1 diabetes mellitus.

INTRODUCTION: Fetuin-A (A2-HS-glycoprotein) is a protein that plays several functions in human physiology and pathophysiology. The role of fetuin-A in type 1 diabetes mellitus (DM) has been less studied. We investigated the serum levels of fetuin-A in type 1 diabetic patients with microalbuminuria. Furthermore, the blocking effect of renin-angiotensin-aldosteron system on serum levels of fetuin-A was assessed. MATERIALS AND METHODS: From January 2010 to May 2011, 32 patients with type 1 DM with confirmed microalbuminuria were included in this study in Isfahan, Iran. Serum fetuin-A levels before and 8 weeks after valsartan administration were measured. In addition, serum lipid profile, creatinine, hemoglobin A1c, and urine microalbuminuria were determined. RESULTS: The mean age of participants was 21.65 +/- 0.38 years. Before valsartan administration, the mean values of fetuin-A were not significantly different between males and females (64.22 +/- 1.77 ng/mL versus 61.39 +/- 3.35 ng/mL, respectively). After valsartan administration, serum levels of fetuin-A and urine albumin-creatinine significantly decreased. A negative correlation was observed between serum fetuin-A level after valsartan administration and serum low-density lipoprotein cholesterol level (P = .007, r = -0.507). CONCLUSIONS: Administration angiotensin receptor blockers concomitantly decreases fetuin-A levels and urine albumin levels.