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Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A.
Lai, CQ, Parnell, LD, Smith, CE, Guo, T, Sayols-Baixeras, S, Aslibekyan, S, Tiwari, HK, Irvin, MR, Bender, C, Fei, D, et al
The American journal of clinical nutrition. 2020;(5):1200-1211
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Abstract
BACKGROUND Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown. OBJECTIVES We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases. METHODS We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator. RESULTS We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with β = 58.4 ± 7.27, P = 8.98 x 10-16 for CHO intake; β = -36.4 ± 5.95, P = 9.96 x 10-10 for FAT intake; and β = 3.30 ± 0.49, P = 1.48 x 10-11 for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases. CONCLUSIONS Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A.Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)-NCT01023750; and the Framingham Heart Study (FHS)-NCT00005121.
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Metabolic Effects of Resistant Starch Type 2: A Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.
Snelson, M, Jong, J, Manolas, D, Kok, S, Louise, A, Stern, R, Kellow, NJ
Nutrients. 2019;(8)
Abstract
Published evidence exploring the effects of dietary resistant starch (RS) on human cardiometabolic health is inconsistent. This review aimed to investigate the effect of dietary RS type 2 (RS2) supplementation on body weight, satiety ratings, fasting plasma glucose, glycated hemoglobin (HbA1c), insulin resistance and lipid levels in healthy individuals and those with overweight/obesity, the metabolic syndrome (MetS), prediabetes or type 2 diabetes mellitus (T2DM). Five electronic databases were searched for randomized controlled trials (RCTs) published in English between 1982 and 2018, with trials eligible for inclusion if they reported RCTs involving humans where at least one group consumed ≥ 8 g of RS2 per day and measured body weight, satiety, glucose and/or lipid metabolic outcomes. Twenty-two RCTs involving 670 participants were included. Meta-analyses indicated that RS2 supplementation significantly reduced serum triacylglycerol concentrations (mean difference (MD) = -0.10 mmol/L; 95% CI -0.19, -0.01, P = 0.03) in healthy individuals (n = 269) and reduced body weight (MD = -1.29 kg; 95% CI -2.40, -0.17, P = 0.02) in people with T2DM (n = 90). However, these outcomes were heavily influenced by positive results from a small number of individual studies which contradicted the conclusions of the majority of trials. RS2 had no effects on any other metabolic outcomes. All studies ranged from 1-12 weeks in duration and contained small sample sizes (10-60 participants), and most had an unclear risk of bias. Short-term RS2 supplementation in humans is of limited cardiometabolic benefit.