High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure

Background Angiotensin‐converting enzyme (ACE) plays a major role in blood pressure regulation and cardiovascular homeostasis. Contrary to the assumption that ACE levels are stable, circulating ACE has been shown to be altered in obesity and weight loss. We sought to examine effects of a high‐saturated‐fat (HF) diet on ACE within the NUtriGenomic Analysis in Twins (NUGAT) study. Methods and Results Forty‐six healthy and nonobese twin pairs initially consumed a carbohydrate‐rich, low‐fat diet over a period of 6 weeks to standardize for nutritional behavior prior to the study, followed by 6 weeks of HF diet under isocaloric conditions. After 6 weeks of HF diet, circulating ACE concentrations increased by 15% (P=1.6×10−30), accompanied by an increased ACE gene expression in adipose tissue (P=3.8×10−6). Stratification by ACE rs4343, a proxy for the ACE insertion/deletion polymorphism (I/D), revealed that homozygous carriers (GG) of the variant had higher baseline ACE concentrations (P=7.5×10−8) and additionally showed a 2‐fold increase in ACE concentrations in response to the HF diet as compared to non‐ or heterozygous carriers (AA/AG, P=2×10−6). GG carriers also responded with higher systolic blood pressure as compared to AA/AG carriers (P=0.008). The strong gene‐diet interaction was confirmed in a second independent, cross‐sectional cohort, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study. Conclusions The HF‐diet‐induced increase of ACE serum concentrations reveals ACE to be a potential molecular link between dietary fat intake and hypertension and cardiovascular disease (CVD). The GG genotype of the ACE rs4343 polymorphism represents a robust nutrigenetic marker for an unfavorable response to high‐saturated‐fat diets. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01631123

High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure

Schüler R, Osterhoff MA, Frahnow T, et al. High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure. Journal of the American Heart Association. 2017;6(1): e004465

Dietary Fat Intake Modulates Effects of a Frequent ACE Gene Variant on Glucose Tolerance with association to Type 2 Diabetes

Schüler R, Osterhoff MA, Frahnow T, et al. Dietary Fat Intake Modulates Effects of a Frequent ACE Gene Variant on Glucose Tolerance with association to Type 2 Diabetes. Scientific Reports. 2017;7(1): 9234

Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans.

CONTEXT: The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms. OBJECTIVE: We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans. DESIGN: Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data. RESULTS: The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes. CONCLUSIONS: Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans