Balanced Caloric Macronutrient Composition Downregulates Immunological Gene Expression in Human Blood Cells—Adipose Tissue Diverges

Abstract

Cardiovascular disease, obesity, and type 2 diabetes are conditions characterized by low-grade systemic inflammation, strongly influenced by lifestyle, but the mechanisms that link these characteristics are poorly understood. Our first objective was to investigate if a normocaloric diet with a calorically balanced macronutrient composition influenced immunological gene expression. Findings regarding the suitability of blood as biological material in nutrigenomics and gene expression profiling have been inconclusive. Our second objective was to compare blood and adipose tissue sample quality in terms of adequacy for DNA-microarray analyses, and to determine tissue-specific gene expression patterns. Blood and adipose tissue samples were collected for gene expression profiling from three obese men before, during, and after a 28-day normocaloric diet intervention where each meal contained an approximately equal caloric load of macronutrients. Time series analyses of blood gene expression revealed a cluster of downregulated genes involved in immunological processes. Blood RNA quality and yield were satisfactory, and DNA-microarray analysis reproducibility was similar in blood and adipose tissue. Gene expression correlation between blood and adipose tissue varied according to gene function, and was especially low for genes involved in immunological and metabolic processes. This suggests that diet composition is of importance in inflammatory processes in blood cells. The findings also suggest that a systems biology approach, in which tissues are studied in parallel, should be employed to fully understand the impact of dietary challenges on the human body.

Methylation and Expression of Immune and Inflammatory Genes in the Offspring of Bariatric Bypass Surgery Patients

“…Although epigenetic signatures have been shown to differ between tissues [38], the overall impact is minor given the known similarities in methylation patterns [39]. Gene expression levels are also known to be tissue-or cell-type dependent but also correlated [40–42] thus justifying the use of blood in clinical studies. Differential gene expression analysis led to a limited number of differentially expressed genes (862) in comparison with the 5698 differentially methylated genes identified.…”

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

“…98 A Mediterranean diet intervention was also found to alter PBMC expression of genes in cardiovascular pathways. 99 Changes in gene expression in blood and adipose tissue from the same individuals (n=3) were reported after an intervention to alter macronutrient content, 100 with divergent transcriptomic responses in the 2 tissues. Adipose tissue gene expression changes were characterized in response to both overfeeding in healthy subjects (n=6) and caloric restriction in obese subjects (n=18), 101 with >100 genes identified as responding to caloric intake.…”

Nutritionally Mediated Oxidative Stress and Inflammation

“…One study that independently assessed the impact of a macronutrient balanced diet found that the intervention diet (30 : 30 : 40 energy percent from carbohydrates, proteins, and fat, resp.) which had higher protein and less fat than the prestudy diet (41 : 19 : 40) yielded immediate and persistent downregulation in immunological genes in PBMCs [66]. Attempts to sort out the key signal have been made, and one study which assessed the impact of both factors in gene expression of adipose tissue in obese women found that caloric restriction had a more profound impact on adipose tissue gene expression than macronutrient composition [67].…”