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Delayed Meal Timing, a Breakfast Skipping Model, Increased Hepatic Lipid Accumulation and Adipose Tissue Weight by Disintegrating Circadian Oscillation in Rats Fed a High-Cholesterol Diet.

ABSTRACT: Background: To investigate whether shifted timing of eating, breakfast skipping, induces alterations in the circadian clock and abnormal lipid metabolism, we have established a delayed meal timing (DMT) protocol for rats, which started eating food 4 h delay. In the present study, control and DMT rats were fed a high-cholesterol diet during zeitgeber time (ZT) 12-24 and ZT 16-4, respectively. The DMT protocol increased the hepatic lipids and epididymal adipose tissue weight without changes in food intake and body weight. The surge in body temperature was delayed by 4 h in the DMT group, suggesting that energy expenditure was decreased in response to DMT. The peaks of the diurnal rhythm of serum non-esterified fatty acids and insulin were delayed by 2 and 4 h due to DMT, respectively. The oscillation peaks of hepatic de novo fatty acid synthesis gene expression was delayed by 4 h in response to DMT, whereas the peak of hepatic clock genes were 2 h delayed or not by DMT. Although metabolic oscillation is considered to be controlled by clock genes, the disintegration rhythms between the clock genes and lipid metabolism-related genes were not observed in rats fed a high-fat diet in our previous study. These data suggest that the circadian rhythm of de novo fatty acid metabolism is regulated by timing of eating, but is not directly controlled by clock genes. The present study suggests that breakfast skipping would complicate fatty liver and body fat accumulation.

SUBMITTER: Kim D

PROVIDER: S-EPMC8280346 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits. OBJECTIVES:The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait. METHODS:We leveraged the statistical power of the UK Biobank (n = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n = 11,963). RESULTS:In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N6-methyladenosine RNA transmethylation (METTL4, YWHAB, and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P = 0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P = 0.095). CONCLUSIONS:Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle.

Project description:Little is known on skipping breakfast and a meal at school, especially considered together. The study identified nutrition knowledge-related, lifestyle (including diet quality, physical activity, and screen time) and socioeconomic correlates of skipping breakfast and a meal at school, considered together or alone and assessed the association of skipping these meals with adiposity markers in Polish teenagers. The sample consisted of 1566 fourth and fifth grade elementary school students (11-13 years). The study was designed as a cross-sectional study. Data related to the consumption of selected food items and meals, physical activity, screen time, sociodemographic factors, and nutrition knowledge (all self-reported) were collected (in 2015-2016) with a short form of a food frequency questionnaire. Respondents reported the usual consumption of breakfast (number of days/week) and a meal or any food eaten at school (number of school days/week) labelled as 'a meal at school'. The measurements of body weight, height, and waist circumference were taken. BMI-for-age ≥25 kg/m2 was considered as a marker of overweight/obesity (general adiposity), while waist-to-height ratio ≥0.5 as a marker of central obesity (central adiposity). A multivariate logistic regression was applied to verify the association between variables. A total of 17.4% of teenagers frequently skipped breakfast (4-7 days/week), 12.9% frequently skipped a meal at school (3-5 school days/week), while 43.6% skipped both of these meals a few times a week. Predictors of skipping breakfast and/or a meal at school were female gender, age over 12 years, urban residence, lower family affluence, lower nutrition knowledge, higher screen time, and lower physical activity. In comparison to "never-skippers," "frequent breakfast skippers" were more likely to be overweight/obese (odds ratio, OR 1.89; 95% confidence interval, 95%CI 1.38, 2.58) and centrally obese (OR 1.63; 95%CI 1.09, 2.44), while skippers a few times a week of both of these meals were more likely to be overweight/obese (OR 1.37; 95%CI 1.06, 1.78). Concluding, we estimated that a large percentage of Polish teenagers (approx. 44%) usually skipped both breakfast and a meal at school a few times a week. Similar predictors of skipping breakfast and predictors of skipping a meal at school were identified. Special attention should be paid to promoting shortening screen time and increasing physical activity and teenagers' nutrition knowledge which are relatively easily modifiable correlates. The study shows that skipping both of these meals a few times a week was associated with general adiposity and also strengthens previous evidence showing the association of frequent skipping breakfast with general and central adiposity.

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Delayed Meal Timing, a Breakfast Skipping Model, Increased Hepatic Lipid Accumulation and Adipose Tissue Weight by Disintegrating Circadian Oscillation in Rats Fed a High-Cholesterol Diet.

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