FATTY LIVER, DIETARY IRON OVERLOAD, SYSTEMIC INSULIN RESISTANCE

[stef2011]

DIETARY IRON OVERLOAD INDUCES VISCERAL ADIPOSE TISSUE INSULIN RESISTANCE ASSOCIATED WITH HYPER-RESISTINEMIA, AND SYNERGIZES WITH OBESITY AND FATTY LIVER IN INDUCING SYSTEMIC INSULIN RESISTANCE

Dr. Luca Valenti [Biography]
Italy  
Background & Aims: Insulin resistance is the key pathogenic feature underlying nonalcoholic fatty liver disease and the metabolic syndrome. Excess body iron is frequently observed in patients with metabolic syndrome, and associated with more severe insulin resistance and organ damage. However, whether iron overload has a causal role in the pathophysiology of these syndromes is not well understood, and likewise the molecular mechanisms involved are still unknown. Aim of this study was to assess the effects of dietary modulation of iron status on glucose metabolism and to investigate the underlying mechanisms in mouse models. Methods: Wild-type or genetically obese (ob/ob) 4 week-old male C57Bl/6 mice were fed for 16 weeks with a standard iron concentration diet (8 mg/kg, control diet, CD, n=15) or with an iron enriched diet (30g/kg, IED, n=15) and high-fructose diet (HFD). Results: IED was associated with increased serum iron and hepatic iron concentration (which was comparable to that observed in patients with metabolic syndrome associated with altered iron status) compared to CD. Despite IED was associated with reduced weight gain, which was explained by reduced visceral adipose tissue mass (VAT; perigonadal fat pad: -60%, p=0.02), it induced a progressive increase in glucose levels due to insulin resistance, which was confirmed by i.p. insulin tolerance test. In ob/ob mice IED led to overt diabetes development, and in mice fed high fructose diet increased insulin resistance by about 100%, associated with decreased VAT mass despite no changes in total body mass, thus suggesting VAT insulin resistance. IED was associated with increased VAT (but not hepatic) insulin resistance, as shown by decreased fasting pAKT/AKT ratio (-80%, p=0.03), and VAT iron accumulation with oxidative stress and unfolded protein response activation. In addition, IED induced increased VAT resistin mRNA levels (p=0.005), which resulted in hyper-resistinemia (p=0.01) and increased VAT expression of SOCS3 (p<0.05), a known resistin target implicated in the pathogenesis of insulin resistance. Conclusions: IED induces insulin resistance in C57/Bl6 mice and synergizes with obesity and dietary factors in the pathogenesis of metabolic complications. We are currently evaluating the relationship between iron metabolism and insulin resistance in VAT.

[stef2011]

thanks stephen, it was only informative i have no iron problems

glutathione is the answer for exess metals but only liposomal or by veins, if it is also the answer for any type of intossication and in case of deadly exposure to radiations like in japan.

according to the type of problems the dose must be increased hourly, for deadly intoxication or radiations or use as an antiviral the doses are like 1-2g or more every hour, i dont remember exact doses but what matters is go high dose.
there are no doses for this compound, it is safe at any dose except for your pokets, the liposomal type is extremely expensive, that's why i use about 800mg daily.13.5g is 80usd

livonlabs is a good producer of these liposomes both for gsh and vit C which are both extremely poorly absorbed by stomach

[StephenCastlecrag]

I have no idea how to lower iron naturally. Apparently it is not a easy matter to determine the level of iron in your body. There are different types of iron and the ways they are stored. The founder of the American hepatitis b maillist , Steve, did a lot of research on this. He lowered his iron level by getting a doctor to draw his blood on a regular basis. I am not suggesting that you do the same, but do try to avoid excessive intake of food that is rich in iron, such as spinach.

[stef2011]

i found that research, glutathione regulates metal in the body and can lower excess

[stef2011]

how to lower iron naturally?

i have read so many articles i dont remember now, zinc or lipo gsh or something else?

[StephenCastlecrag]

Background & Aims
Iron overload does seem to affect liver diseases such as HBV and HCV.

http://www.gastrojournal.org/article/S0016-5085%2811%2900159-4/abstract

Iron may influence severity and progression of non-hemochromatotic liver diseases. Our aim was to assess the relationship of iron and HFE genetic variations to progression and outcomes in the HALT-C Trial and whether PegIFN therapy influenced iron variables.
Methods

Participants were randomized to receive long-term PegIFN [n = 400] or no therapy [n = 413] for 3.5 y, with follow-up for up to 8.7 y [median 6.0 y]. Associations of patient characteristics with iron variables at baseline and over time were carried out using Kaplan-Meier analyses, Cox regression models, and repeated measures analysis of covariance.
Results

Participants who developed clinical outcomes [CTP > 7, ascites, encephalopathy, variceal bleeding, SBP, HCC, death] had significantly higher baseline scores for stainable iron in hepatocytes and in portal tract cells than those without. There were significant direct correlations between stainable iron in portal triads and lobular and total Ishak inflammatory and fibrosis scores [P < 0.0001]. Iron in triads at baseline increased risk of outcomes (HR = 1.35, P = 0.02). Stainable iron in hepatocytes decreased, whereas that in portal stromal cells increased significantly [P < 0.0001] over time. Serum iron and TIBC fell significantly over time [P < 0.0001], as did serum ferritin [P = 0.0003]. Chronic PegIFN treatment did not affect stainable iron. HFE genetic variations did not correlate with outcomes, including development of hepatocellular carcinoma.
Conclusions

Stainable iron in hepatocytes and portal tract cells is a predictor of progression and clinical and histological outcomes in advanced chronic hepatitis C. Chronic low-dose PegIFN therapy did not improve outcomes, nor iron variables.