Abstract
Smaller cross-sectional studies and bariatric surgery trials suggest that weight loss may change the expression of genes in adipose tissue that have been implicated in the development of metabolic diseases, but well-powered intervention trials are lacking. In post hoc analyses of data from a 12-week dietary intervention trial initially designed to compare metabolic effects of intermittent vs. continuous calorie restriction, we analyzed the effects of overall weight loss on the subcutaneous adipose tissue (SAT) transcriptome. Changes in the transcriptome were measured by microarray using SAT samples of 138 overweight or obese individuals (age range: 35–65 years, BMI range: 25–40, non-smokers, non-diabetics). Participants were grouped post hoc according to the degree of their weight loss by quartiles (average weight loss in quartiles 1 to 4: 0%, −3.2%, −5.9%, and −10.7%). Candidate genes showing differential expression with weight loss according to microarray analyses were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and fold changes (FCs) were calculated to quantify differences in gene expression. A comparison of individuals in the highest vs. the lowest weight loss quartile revealed 681 genes to be differentially expressed (corrected p < 0.05), with 40 showing FCs of at least 0.4. Out of these, expression changes in secreted frizzled-related protein 2 (SFRP2, FC = 0.65, p = 0.006), stearoyl-CoA desaturase (SCD, FC = −1.00, p < 0.001), and hypoxia inducible lipid droplet-associated (HILPDA, FC = −0.45, p = 0.001) with weight loss were confirmed by RT-qPCR. Dietary weight loss induces significant changes in the expression of genes implicated in lipid metabolism (SCD and HILPDA) and WNT-signaling (SFRP2) in SAT.
Highlights
Obesity, characterized by excessive accumulation of adipose tissue, is a risk factor for major chronic diseases such as type 2 diabetes, cardiovascular diseases, and many types of cancer [1,2,3].Dysfunctional adipose tissue signaling is a hallmark of obesity and drives its comorbidities, e.g., via increased release of inflammatory factors, altered adipokine profiles, and constant anabolic stimuli by growth factors and hormones [3,4].For the prevention of pathophysiological complications among overweight or obese people, it has been recommended to aim at 5–10% weight loss by calorie restriction (CR) approaches and/or increase in physical activity levels [5]
Many previous studies have been cross-sectional studies with inter-individual comparisons of lean and obese individuals [8,9], or bariatric surgery interventions with substantial weight loss [10,11], while not much is known about the effects of diet-induced weight loss on the adipose tissue transcriptome from larger intervention trials
Only the expression of specific candidate genes was analyzed in many previous studies, while there is a lack of comprehensive transcriptome-wide, i.e., microarray-derived gene expression data from dietary intervention trials
Summary
Obesity, characterized by excessive accumulation of adipose tissue, is a risk factor for major chronic diseases such as type 2 diabetes, cardiovascular diseases, and many types of cancer [1,2,3].Dysfunctional adipose tissue signaling is a hallmark of obesity and drives its comorbidities, e.g., via increased release of inflammatory factors, altered adipokine profiles, and constant anabolic stimuli by growth factors and hormones [3,4].For the prevention of pathophysiological complications among overweight or obese people, it has been recommended to aim at 5–10% weight loss by calorie restriction (CR) approaches and/or increase in physical activity levels [5]. The central role of adipose tissue accumulation, in the visceral compartment, is undisputed, there is limited knowledge on the reversibility of obesity-induced alterations in adipose tissue function with weight loss. Adipose tissue gene expression has been used to investigate obesity-related metabolic dysfunction in human trials, as it may provide the basis for the understanding of dysfunctional adipose tissue signaling and its reversibility by weight loss [6,7]. Many previous studies have been cross-sectional studies with inter-individual comparisons of lean and obese individuals [8,9], or bariatric surgery interventions with substantial weight loss [10,11], while not much is known about the effects of diet-induced weight loss on the adipose tissue transcriptome from larger intervention trials. Only the expression of specific candidate genes was analyzed in many previous studies, while there is a lack of comprehensive transcriptome-wide, i.e., microarray-derived gene expression data from dietary intervention trials
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