A study published in the Journal of Nutritional Biochemistry investigated the changes in gene expressions during an overfeeding episode. It demonstrated that supplementation of grape polyphenols in healthy lean men modulates the expression of genes related to adipose tissue angiogenesis.
Research Paper: Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial. Image Credit: Basico / Shutterstock
Obesity has become a significant public health concern worldwide due to its ability to induce severe pathologies, including cardiovascular disease, type two diabetes, metabolic syndrome, non-alcoholic fatty liver disease, and certain cancers. There is an imminent need to discover new strategies to prevent obesity.
Accumulation of fat mass in the adipose tissue is a major hallmark of obesity. Overfeeding induces certain adaptive reactions in the body that significantly modulate gene expressions in the adipose to support lipid storage and weight gain. Understanding these fat accumulation mechanisms is key to identifying novel targets to tackle the issue.
Most genes studied here are associated with lipid metabolism and storage, oxidative phosphorylation, angiogenesis, and extracellular matrix remodeling in the subcutaneous adipose tissue.
In the current study, scientists have investigated the effect of polyphenol supplementation on the adipose tissue gene expression profile in healthy lean men undergoing an overfeeding trial.
Polyphenols are a group of plant-derived bioactive compounds with antioxidant, anti-inflammatory, and anticancer properties. These compounds are known to have beneficial effects on cardiovascular and metabolic diseases. Moreover, there is evidence suggesting that polyphenols might have a positive impact on obesity-related complications.
The study was conducted on 42 healthy lean men participating in an overfeeding trial. During the 31-day overfeeding trial, the participants were provided with over 50% of their total energy expenditure. The excess energy was provided by adding energy-rich food products, such as soda, chocolate bread, chocolate bars, and chips, between their usual meals.
The participants were divided into two groups. The intervention group was supplemented with 2 gm per day of grape polyphenols. The control group was supplemented with placebo capsules.
Abdominal subcutaneous adipose tissue biopsy samples were collected from the participants and underwent ribonucleic acid (RNA) sequencing analysis to determine gene expression profiles.
Both intervention and control groups observed a comparable induction in body weight, fat mass, and subcutaneous adipose volume.
Adipose tissue gene expression profile
The RNA sequencing findings revealed that overfeeding caused differential expression of 352 genes in polyphenol-supplemented participants. Of these genes, 118 were downregulated, and 234 were upregulated.
The functional analysis of these genes revealed the highest association with lipid metabolism, followed by thermogenesis, mitochondrial transport, aerobic respiration, angiogenesis, fat cell differentiation, inflammation, and hypoxic response.
The RNA sequencing of samples collected from placebo-supplemented participants identified 163 differentially expressed genes related to overfeeding. Of these genes, 46 were downregulated, and 117 were upregulated.
The functional analysis revealed that these genes are associated with lipid metabolism, angiogenesis, extracellular matrix, insulin response, and oxidative phosphorylation.
In both intervention and control groups, 74 genes were identified to have similar modulation due to overfeeding. These genes were associated with lipid, cholesterol, and organophosphate metabolism.
Effects of polyphenols on adipose tissue gene expression
The analysis of overfeeding-related differentially expressed genes in both groups revealed an opposite pattern of gene expression regulation between the groups. 812 genes were differentially regulated between the groups in response to overfeeding.
Of these genes, 41 angiogenesis-related genes showed reduced expression profiles in the polyphenol-supplemented group.
Reduced angiogenesis in the polyphenol-supplemented group was further confirmed by the immunohistochemistry findings that showed reduced expression of an endothelial cell marker in this group.
An in vitro experiment with human umbilical vein endothelial cells was conducted to determine several polyphenols' effects on endothelial cell migration. The findings revealed that two polyphenols, quercetin and isorhamnetin, significantly inhibited endothelial cell migration. In contrast, 3-hydroxyphenyl acetic acid was found to increase migration.
The study reveals that polyphenol supplementation does not change the expression of genes related to lipid metabolism in response to overfeeding. However, polyphenols reduce angiogenesis in the adipose tissue, potentially preventing adipose tissue expansion during overfeeding-induced weight gain.