Results of objective 1: We have measured a type of epigenetic “switch” called DNA methylation (DNAm) in 100 overweight individuals following either a low-carbohydrate diet (LCD) or a low-fat diet (LFD). We have identified two DNAm biomarkers that are strong predictors of baseline weight (the initial weight of the study participants) and that show more than 30% DNAm change after weight loss in the individuals who lost the greatest amount of weight ("biggest losers", n=8). This indicates that our epigenetic biomarkers can capture changes in body weight in both directions — gaining weight and losing weight — and may, therefore, be used for early detection of obesity-associated disease as well as personalized monitoring of its reversal. Strikingly, both biomarkers are located in a gene called ABCG1, a diabetes-related gene involved in insulin secretion. DNAm at ABCG1 has been shown to be a highly predictive marker of type-2 diabetes mellitus (T2DM) in a recent large-scale longitudinal epigenome-wide association study (EWAS, Wahl et al. Nature 2017). This exciting finding makes ABCG1 an extremely promising candidate as a DNAm marker of T2DM status and reversal. Follow up studies with the University of Vienna will test this hypothesis by measuring ABCG1 DNAm in T2DM patients and non-diabetic control subjects.
Results of objective 2: We have compared weight loss and diet adherence between 609 men and women following an LCD or LFD. Our results indicate that men lose significantly more weight and body fat on LCD than LFD, whereas women lose the same amount of weight and body fat on either diet. Interestingly, however, women were able to stick much better to LFD than LCD, possibly due to a perception of dietary fats as “fattening”. This suggests that women may increase their weight loss success on LCD by overcoming their fear of fat. These findings may guide healthcare providers to develop dietary strategies that take into account the different food attitudes of men and women to overcome potential gender-related roadblocks to weight-loss success.
Results of objective 3: We have found that a ketogenic diet or an Ornish diet induce distinct metabolic changes, despite inducing similar weight loss and reduction in blood glucose and insulin. A ketogenic diet induces improved levels of two metabolic markers compared to an Ornish diet: a significantly greater decrease in triglycerides and a concomitant significantly greater increase in “good” HDL cholesterol. On the other side, an Ornish diet induces a significantly greater decrease in LDL cholesterol, which is associated with decreased risk for cardiovascular disease. These diet-specific metabolic changes may inform the personalized treatment of metabolic imbalances using diets with extreme low-carbohydrate content (ketogenic diet) or extreme low-fat content (Ornish diet).
Dissemination
Project video:
soon available on the University website(opens in new window)Publications
• A systematic review of studies of DNA methylation in the context of a weight loss intervention”. Epigenomics. 2017 May;9(5):769-787.
https://osf.io/28c5x/(opens in new window)• The Effect of Nutrition on Epigenetic Status, Growth, and Health.
https://osf.io/jsb73/(opens in new window)• Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial, The American Journal of Clinical Nutrition, Volume 109, Issue 2, February 2019, Pages 433–441
https://osf.io/sd5rb/(opens in new window)Submitted Manuscript
• Examining differences between overweight women and men in 12-month weight loss study comparing healthy low-carbohydrate vs. low-fat diets.
Other manuscripts in preparation
• Identification of weight loss-associated DNA methylation (DNAm) markers
• Effects of a Ketogenic-like, Mediterranean-like and Ornish-like Diet on Weight Loss and Chronic Disease Risk Factors
