Literature Review | March 2019

Select a topic from the list below:

• Dietary antioxidant capacity and risk of type 2 diabetes in the large prospective E3N-EPIC cohort
   
• HIF-1α protects against oxidative stress by directly targeting mitochondria

Dietary antioxidant capacity and risk of type 2 diabetes in the large prospective E3N-EPIC cohort

Francesca Romana Mancini, Aurélie Affret, Courtney Dow, Beverley Balkau, Fabrice Bonnet, Marie-Christine Boutron-Ruault & Guy Fagherazzi, Diabetologia (2018) 61:308–316, DOI: 10.1007/s00125-017-4489-7

There is a high amount of evidence from both experimental and clinical studies suggesting that oxidative stress plays a major role in the pathogenesis of type 2 diabetes. It has been elucidated that high levels of free radicals and decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation and development of insulin resistance. Also, previous studies have highlighted that an increased intake of dietary antioxidants such as vitamin E and vitamin C increase insulin sensitivity as well as reduce fasting and post-meal blood glucose and improve HbA_1clevels. The study by Mancini et alinvestigated the relationship between total antioxidant capacity and risk of type 2 diabetes in the E3N-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which consisted of a large cohort of French women. This cohort was initiated in France in 1990 to primarily study the main risk factors for cancer and severe chronic conditions in women. It is the French constituent of the large EPIC study, and the EPIC sub-study devoted to diabetes: Interaction of Genetic and Lifestyle Factors on the Incidence of Type 2 Diabetes (InterAct). The E3N-EPIC cohort included 98,995 French women born between 1925 and 1950, insured by the Mutuelle Générale de l’Education Nationale (MGEN), a national teachers’ health insurance plan. According to the details mentioned in this paper on the study population, out of the 64,223 women (mean age 52 ± 7 years) from the French E3N-EPIC cohort, 1751 women had been validated to be contracted with type 2 diabetes during 15 years of follow-up. The total antioxidant capacity was estimated with the ferric ion-reducing antioxidant power (FRAP) method. Adjusted Cox proportional hazards regression models were used to calculate Hazards Regression (HR) and 95% Confidence Intervals (CIs) for the associations between total antioxidant capacity and type 2 diabetes risk, adjusted for potential confounders. Mancini et al mention that compared with women in the lowest quintile, women in the third, fourth and fifth quintiles had total antioxidant capacity HRs of 0.74 (95% CI 0.63, 0.86), 0.70 (95% CI 0.59, 0.83) and 0.73 (95% CI 0.60, 0.89), respectively. The inverse association between total antioxidant capacity and the risk of type 2 diabetes was linear up to values of 15 mmol/day of fasting blood glucose, after which the effect reached a plateau. Overall, the findings of the study suggest that the total antioxidant capacity of the diet may play a role in reducing the risk of type 2 diabetes in middle-aged women. One particular strength of this study was the ability to include a large sample size and the prospective design of the E3N-EPIC cohort, which allowed the research team to perform sensitivity analyses while keeping sufficient statistical power to detect associations, making the reverse causation hypothesis unlikely. (Prepared by Viduranga Waisundara, Australian College of Business & Technology – Kandy Campus, Peradeniya Road, Kandy, Sri Lanka)

HIF-1α protects against oxidative stress by directly targeting mitochondria

Li HS, Zhou YN, Li L, Li SF, Long D, Chen XL, Zhang JB, Feng L, Li YP, Redox Biology. 2019 Jan 14:101109. doi: 10.1016/j.redox.2019.101109 [Epub ahead of print]

Hypoxia inducible factor 1 (HIF-1) is a transcription factor that upregulates gene expressions in response to hypoxic conditions. This biological function of HIF-1 requires the translocation of HIF-1’s subunit, i.e., HIF-1α, to the nucleus whereby it binds to hypoxia-response elements to induce protein synthesis, particularly that of heat shock proteins. It has been thought that HIF-1α could target other organelles and protect against oxidative stress. Indeed, in a recent paper published by Li et alreported the translocation of HIF-1α into mitochondria upon hypoxic and oxidative challenges. Using Hela cells and other cell lines, the authors detected the existence of HIF-1α in mitochondrial fractions induced by CoCl₂(hypoxic conditions) and hydrogen peroxide (oxidative conditions). The authors further found that mitochondrial oxidative stress was attenuated by this HIF-1α translocation and this protective effect was independent of HIF-1α ‘s transcription activity. The significance of this moonlighting function of HIF-1α in mitochondria was demonstrated in liver fibrosis induced by CCl₄whereby HIF-1α was detected in fibrotic hepatocytes.  Notwithstanding, the mechanism by which mitochondrial HIF-1α protects against oxidative stress remains to be elucidated. (Reviewed by Liang-Jun Yan, University of North Texas Health Science Center)