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Diet-induced weight loss leads to a switch in gene regulatory network control in the rectal mucosa.

ABSTRACT: Weight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women.We identified significantly greater regulatory targeting of glucose transport pathways in the post-weight loss regulatory network, including "regulation of glucose transport" (FDR=0.02), "hexose transport" (FDR=0.06), "glucose transport" (FDR=0.06) and "monosaccharide transport" (FDR=0.08). These findings were not evident by gene expression analysis alone. Network analysis also suggested a regulatory switch from NF?B1 to MAX control of MYC post-weight loss.These network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss.

SUBMITTER: Vargas AJ

PROVIDER: S-EPMC5121035 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Diet-induced weight loss leads to a switch in gene regulatory network control in the rectal mucosa.

Vargas Ashley J AJ Quackenbush John J Glass Kimberly K

Genomics 20160811 3-4

<h4>Background</h4>Weight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women.<h4>Results</h4>We identified significantly greater regulatory targeting of ...[more]

PMID: 27524493

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Project description:Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

Dataset Information

Diet-induced weight loss leads to a switch in gene regulatory network control in the rectal mucosa.

Publications

Diet-induced weight loss leads to a switch in gene regulatory network control in the rectal mucosa.

Similar Datasets

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