Although oxidative stress has been implicated in development of gut pathologies, its role in intestinal fat transport has not been investigated. We assessed the effect of Fe(2+)-ascorbate-mediated lipid peroxidation on lipid synthesis, apolipoprotein biogenesis, and lipoprotein assembly and secretion. Incubation of postconfluent Caco-2 cells with iron(II)-ascorbate (0.2 mM/2 mM) in the apical compartment significantly promoted malondialdehyde formation without affecting sucrase activity, transepithelial resistance, DNA and protein content, and cell viability. However, addition of the oxygen radical-generating system reduced 1) [(14)C]oleic acid incorporation into cellular triglycerides (15%, P < 0.0002) and phospholipids (16%, P < 0.0005); 2) de novo synthesis of cellular apolipoprotein A-I (apo A-I) (18%, P < 0.05), apo A-IV (38%, P < 0.05), and apo B-48 (45%, P < 0.003) after [(35)S]methionine addition; and 3) production of chylomicrons (50%), VLDL (40%), LDL (37%), and HDL (30%) (all P < 0.0001). In contrast, increased total cellular cholesterol formation (96%, P < 0.0001), assayed by [(14)C]acetate incorporation, was noted, attributable to marked elevation (70%, P < 0.04) in activity of DL-3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The ratio of Acyl-CoA to cholesterol acyltransferase, the esterifying cholesterol enzyme, remained unchanged. Fe(2+)-ascorbate-mediated lipid peroxidation modifies intracellular fat absorption and may decrease enterocyte efficiency in assembling and transporting lipids during gut inflammation.

Bacterial endotoxin and prooxidants may overwhelm antioxidant defenses and become deleterious to enterocyte function, whereas butyric acid and BHT may provide antioxidant protection.

We showed recently that iron + ascorbate can impair the assembly of intestinal lipoproteins. However, we could not determine whether these changes were caused by iron + ascorbate-mediated lipid peroxidation per se. We therefore conducted studies to evaluate how antioxidants antagonize the iron + ascorbate-induced derangements. To this end, Caco-2 cells, a reliable experimental intestinal model, were incubated with iron + ascorbate (0.2 mmol/L each) alone or with different concentrations of catalase, mannitol, tocopherol or BHT. Exposing Caco-2 cells to iron + ascorbate increased malondialdehyde levels fourfold (P < 0.0001); this effect was decreased markedly (P < 0.02) in the presence of BHT. Furthermore, BHT normalized the abnormal intracellular events involved in fat absorption, i.e., lipid esterification, cholesterol synthesis and apolipoprotein production. On the other hand, it did not fully restore the secretion of lipids and lipoproteins. Thus, our current data imply that iron + ascorbate-catalyzed lipid peroxidation is partially responsible for the disturbances observed in intestinal lipid transport.

Objective: The objective of this cross-sectional study was to assess whether optimism is associated with body mass index (BMI), eating behavior and eating disorders (EDs) in a population-based study. Method: In 2016, a total of 32,805 participants aged ≥18 years from the NutriNet-Santé cohort completed the Life Orientation Test-Revised, assessing dispositional optimism. Height and weight were self-reported. Eating behavior was assessed with the revised 21-item Three-Factor Eating Questionnaire. Risk of EDs was evaluated with the Sick-Control-One-Fat-Food Questionnaire. Linear and Logistic regression was used to analyze the association between optimism, BMI categories, eating behavior and ED risk, controlling for sociodemographic, lifestyle and depressive symptom characteristics. Results: Our sample was composed of 73.5% women, and the mean age was 55.39 ± 13.70 years. More optimistic participants were less likely to be underweight (OR = 0.82; 95% CI: 0.75, 0.89), or obese, particularly class III obese (BMI ≥40 kg/m 2) (OR = 0.69; 95% CI: 0.56, 0.84) compared with less optimistic individuals. Optimism was negatively associated with cognitive restraint (β = −.07; 95%CI: −0.08; −0.06), emotional eating (β = −.17; 95% CI: −0.19, −0.16) and uncontrolled eating (β = −.10; 95% CI: −0.11, −0.09). In addition, more optimistic participants had a lower risk of EDs (OR = 0.60; 95% CI: 0.56, 0.64). Discussion: Our findings showed that optimism was associated with weight status, eating behavior and risk of EDs in both women and men. The causal structure of the underlying observed association remains unclear and should be further investigated.