Pathophysiology of NASH: Insulin Resistance, Free Fatty Acids and Oxidative Stress

Increase in plasma free fatty acids (FFAs) concentrations may cause cellular damage via the induction of oxidative stress. The aim of this present study was to investigate FFAs and oxidative stress in hypertension co-morbidly occurring with Type 2 Diabetes Mellitus (T2DM). Age and sex matched control subjects (n=150) and patients (n=470) [hypertensive nondiabetics (HND, n=179), normotensive diabetics (ND, n=132), hypertensive diabetics (HD, n=159)] presenting at the Medical Out-Patient Clinic of the State Hospital, Abeokuta, Nigeria were recruited. Fasting plasma glucose, creatinine, urea, FFAs, thiobarbituric acid reactive substances (TBARS) were determined spectrophotometrically. The presence of either or both diseases resulted in significant increase (p<0.05) in the plasma FFAs and oxidative stress marker-TBARS in different compartments (plasma, erythrocytes andlipoproteins) for both male and female patients when compared with their control counterparts. The increase in FFAs was more marked in comorbidity female when compared with other female patients. There was significant (p<0.05) difference in gender FFAs concentrations. In both controls and patients, FFAs in plasma are significantly (p<0.05) higher in male when compared with their female counterparts. This research revealed biochemical variations in hypertension co-morbidly occurring with T2DMcharacterised by gender-related elevation in FFAs and enhanced oxidative stress. Plasma FFAs might be a good biomarker predicting the occurrence and development of hypertension and/or T2DM.

Download Full-text

Reduced Oxidative Stress Contributes to the Lipid Lowering Effects of Isoquercitrin in Free Fatty Acids Induced Hepatocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/313602 ◽

2014 ◽

Vol 2014 ◽

pp. 1-18 ◽

Cited By ~ 28

Author(s):

Waseem Hassan ◽

Gao Rongyin ◽

Abdelkader Daoud ◽

Lin Ding ◽

Lulu Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Lipid Metabolism ◽

Free Fatty Acids ◽

Molecular Level ◽

Lipid Lowering ◽

Hepatic Lipid Metabolism ◽

Ampk Pathway ◽

Coculture Model ◽

And Oxidative Stress

Oxidative stress interferes with hepatic lipid metabolism at various levels ranging from benign lipid storage to so-called second hit of inflammation activation. Isoquercitrin (IQ) is widely present flavonoid but its effects on hepatic lipid metabolism remain unknown. We used free fatty acids (FFA) induced lipid overload and oxidative stress model in two types of liver cells and measured cell viability, intracellular lipids, and reactive oxygen species (ROS) within hepatocytes. In addition, Intracellular triglycerides (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) were examined. A novelin vitromodel was used to evaluate correlation between lipid lowering and antioxidative activities. Furthermore, 34 major cytokines and corresponding ROS levels were analyzed in FFA/LPS induced coculture model between hepatocytes and Kupffer cells. At molecular level AMPK pathway was elucidated. We showed that IQ attenuated FFA induced lipid overload and ROS within hepatocytes. Further, IQ reversed FFA induced increase in intracellular TG SOD and MDA. It was shown that antioxidative activity of IQ correlates with its lipid lowering potentials. IQ reversed major proinflammatory cytokines and oxidative stress in FFA/LPS induced coculture model. Finally, AMPK pathway was found responsible for metabolic benefits at molecular level. IQ strikingly manifests antioxidative and related lipid lowering activities in hepatocytes.

Download Full-text