Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.

BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNFα and IL-6), mitochondrial and total reactive oxygen species (ROS) production, glutathione levels, antioxidant enzymes activity, total antioxidant status, mitochondrial membrane potential and ER stress marker expression levels (glucose-regulated protein (GRP78), spliced X-box binding protein 1 (XBP1), P-subunit 1 alpha (P-eIF2α) and activating transcription factor 6 (ATF6). RESULTS: The MAO and MADO groups showed higher blood pressure, atherogenic dyslipidemia, insulin resistance and inflammatory profile than that of MHO subjects. Total and mitochondrial ROS production was enhanced in MAO and MADO patients, and mitochondrial membrane potential and catalase activity differed significantly between the MADO and MHO groups. In addition, decreases in glutathione levels and superoxide dismutase activity were observed in the MADO vs MAO and MHO groups. GRP78 and CHOP protein and gene expression were higher in the MAO and MADO groups with respect to MHO subjects, and sXBP1 gene expression was associated with the presence of diabetes. Furthermore, MAO patients exhibited higher levels of ATF6 than their MHO counterparts. Waist circumference was positively correlated with ATF6 and GRP78, and A1c was positively correlated with P-Eif2α. Interestingly, CHOP was positively correlated with TNFα and total ROS production and GRP78 was negatively correlated with glutathione levels. CONCLUSIONS: Our findings support the hypothesis that both inflammation and oxidative stress are involved in the induction of ER stress signaling pathways in the leukocytes of metabolically unhealthy obese vs healthy obese subjects.

Relation between lipoprotein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism (SCH) is a common condition associated with increased cardiovascular risk. A standard treatment is yet to be established, as there is no consensus on the TSH cut-off values which should be used as indicators. Thus, the aim of this study was to assess cardiovascular risk in patients with SCH and to differentiate it according to TSH levels. DESIGN: This was an observational study conducted in an academic medical centre. PATIENTS: The study population consisted of 95 middle-aged women recently diagnosed with SCH and 65 euthyroid controls. MEASUREMENTS: We measured anthropometric parameters, lipid cardiovascular risk markers and lipoprotein subclasses of HDL and LDL. RESULTS: Patients with SCH exhibited a significant increase in triglycerides and atherogenic index of plasma and a significant reduction in HDL-cholesterol with respect to the control group after adjusted by age and BMI. A similar lipid profile was observed in both SCH groups. However, patients with TSH levels higher than 10 mIU/l showed a significant reduction in LDL particle size, which was associated with a higher prevalence of atherogenic pattern B. CONCLUSIONS: Our findings indicate that cardiovascular risk is affected in patients with TSH levels over 10 mIU/l, who have a lipid profile characteristic of atherogenic dyslipidemia.

Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles.

BACKGROUND/OBJECTIVES: The importance of both low-density lipoprotein cholesterol (LDLc) size and the apolipoprotein E (Apo E) in the atherogenic process is known, but there is little information with regard to the effect of phytosterols (PS) on these parameters. The aim of this study was to evaluate the influence of PS on lipid profile and LDLc size according to Apo E genotype. SUBJECTS/METHODS: This was a randomized parallel trial employing 75 mild-hypercholesterolemic subjects and consisting of two 3-month intervention phases. After 3 months of receiving a standard healthy diet, subjects were divided into two intervention groups: a diet group (n=34) and a diet+PS group (n=41) that received 2 g/day of PS. Total cholesterol (TC), triacylglycerols, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, Apo A-I and B-100, LDLc size and Apo E genotype were determined. RESULTS: Patients receiving PS exhibited a significant decrease in TC (5.1%), LDLc (8.1%), non-HDLc (7.4%) and Apo B-100/Apo A-I ratio (7.7%), but these effects did not depend on Apo E genotype. No significant changes were found in lipid profile according to Apo E genotype when patients following dietary recommendations were considered as a whole population or separately. No variations in LDLc size were observed in any of the intervention groups. CONCLUSION: The results of this study show that Apo E genotype does not have an impact on the lipid response to PS as a cholesterol-lowering agent in mild-hypercholesterolemic patients. Furthermore, the evidence obtained confirms that LDLc particle size is not modified when PS are added to a standard healthy diet.