Effects of Dietary Fat to Carbohydrate Ratio on Obesity Risk Depending on Genotypes of Circadian Genes.

Jinyoung Shon,Yoon Jung Park,Yerim Han

doi:10.3390/nu14030478

Abstract

Although the impacts of macronutrients and the circadian clock on obesity have been reported, the interactions between macronutrient distribution and circadian genes are unclear. The aim of this study was to explore macronutrient intake patterns in the Korean population and associations between the patterns and circadian gene variants and obesity. After applying the criteria, 5343 subjects (51.6% male, mean age 49.4 ± 7.3 years) from the Korean Genome and Epidemiology Study data and nine variants in seven circadian genes were analyzed. We defined macronutrient intake patterns by tertiles of the fat to carbohydrate ratio (FC). The very low FC (VLFC) was associated with a higher risk of obesity than the optimal FC (OFC). After stratification by the genotypes of nine variants, the obesity risk according to the patterns differed by the variants. In the female VLFC, the major homozygous allele of CLOCK rs11932595 and CRY1 rs3741892 had a higher abdominal obesity risk than those in the OFC. The GG genotype of PER2 rs2304672 in the VLFC showed greater risks for obesity and abdominal obesity. In conclusion, these findings suggest that macronutrient intake patterns were associated with obesity susceptibility, and the associations were different depending on the circadian clock genotypes of the CLOCK, PER2, and CRY1 loci.

Highlights

The circadian clock governs 24 h rhythms and regulates the sleep–wake cycle
We explored macronutrient intake patterns in a Korean midlife population and observed associations between patterns and circadian clock gene variants and obesity
The prevalence of obesity and abdominal obesity increased in the very low FC (VLFC) compared to the optimal FC (OFC) in females

Summary

Introduction

The circadian clock governs 24 h rhythms and regulates the sleep–wake cycle. Circadian rhythms influence metabolism and physiological processes [1]. The circadian core genes, including the circadian locomotor output cycle kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator-like (ARNTL, known as BMAL1), period homolog (PER1, PER2), and cryptochrome (CRY1, CRY2) regulate the circadian rhythm mechanism [1,3]. The ARNTL-CLOCK complex drives the transcription of PER and CRY genes by binding to enhancer elements. Increased proteins of PER and CRY inhibit ARNTL-CLOCK-mediated transcription. This transcription–translation negative feedback loop leads the circadian rhythm, which takes 24 h [3,4]

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