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Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation
- Source :
- PLoS Genetics, PLoS Genetics, Public Library of Science, 2012, 8 (9), pp.e1002959. ⟨10.1371/journal.pgen.1002959⟩, PLoS Genetics, 2012, 8 (9), pp.e1002959. ⟨10.1371/journal.pgen.1002959⟩, PLoS Genetics, Vol 8, Iss 9, p e1002959 (2012), Plos Genetics, 8(9):e1002959. Public Library of Science, PLoS Genetics, Public Library of Science, 2012, 8 (9), pp.e1002959. 〈10.1371/journal.pgen.1002959〉, Plos Genetics 9 (8), . (2012), Dadun. Depósito Académico Digital de la Universidad de Navarra, instname
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases.<br />Author Summary In obesity, an excess of adipose tissue is associated with dyslipidemia and diabetic complications. Gene expression is under the control of various genetic and environmental factors. As a central organ for the control of metabolic disturbances in conditions of both weight gain and loss, a comprehensive understanding of the control of adipose tissue gene expression is of paramount interest. We analyzed adipose tissue gene expression in obese individuals from the DiOGenes protocol, one of the largest dietary interventions worldwide. We found evidence for composite control of adipose tissue gene expression by nutrition, metabolic syndrome, body mass index, sex, and genotype with two main novel features. First, we observed a preeminent effect of sex on adipose tissue gene expression, which was independent of nutritional status, fat mass, and sex chromosomes. Second, the control of gene expression by cis genetic factors was unaffected by sex and nutritional status. Altogether, the effects of the investigated factors were most often independent of each other. Comprehension of the relative importance of environmental and individual factors that control the expression of human adipose tissue genes may help deciphering strategies aimed at controlling adipose tissue function during metabolic disorders.
- Subjects :
- Male
Cancer Research
Adipose tissue
Gene Expression
[SDV.GEN] Life Sciences [q-bio]/Genetics
Body Mass Index
0302 clinical medicine
Weight loss
Gene expression
Molecular Cell Biology
[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics
Genetics (clinical)
2. Zero hunger
Regulation of gene expression
Gene expression regulation
Metabolic Syndrome
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
0303 health sciences
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie
Genomics
[ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
3. Good health
Santé publique et épidémiologie
obésité
Adipose Tissue
Medicine
Female
medicine.symptom
Research Article
medicine.medical_specialty
lcsh:QH426-470
Calorie restriction
Médecine humaine et pathologie
030209 endocrinology & metabolism
Biology
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
03 medical and health sciences
Sex Factors
Internal medicine
[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology
Weight Loss
medicine
Genetics
Genome-Wide Association Studies
Humans
Obesity
Molecular Biology
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
Nutrition
Caloric Restriction
Regulatory Networks
[SDV.GEN]Life Sciences [q-bio]/Genetics
Lipogenesis
Computational Biology
Human Genetics
medicine.disease
lcsh:Genetics
Endocrinology
Gene Expression Regulation
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie
Human health and pathology
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Metabolic syndrome
Genome Expression Analysis
Energy Intake
[ SDV.GEN ] Life Sciences [q-bio]/Genetics
Body mass index
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- Language :
- English
- ISSN :
- 15537390 and 15537404
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics, PLoS Genetics, Public Library of Science, 2012, 8 (9), pp.e1002959. ⟨10.1371/journal.pgen.1002959⟩, PLoS Genetics, 2012, 8 (9), pp.e1002959. ⟨10.1371/journal.pgen.1002959⟩, PLoS Genetics, Vol 8, Iss 9, p e1002959 (2012), Plos Genetics, 8(9):e1002959. Public Library of Science, PLoS Genetics, Public Library of Science, 2012, 8 (9), pp.e1002959. 〈10.1371/journal.pgen.1002959〉, Plos Genetics 9 (8), . (2012), Dadun. Depósito Académico Digital de la Universidad de Navarra, instname
- Accession number :
- edsair.doi.dedup.....cfeb8c97df1376a1b4e1aa6112adb220