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Adipose tissue network analyses reveal negative association between GDF15 and BMI during weight management intervention.

ABSTRACT: CONTEXT: Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. OBJECTIVE: To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during three steps of a two-phase dietary intervention (DI). RESULTS: During LCD, 5 modules were found, 3 of which including at least 1 bio-clinical variable. Especially, the change in BMI was connected to changes in mRNA level of genes with Inflammatory response signature. In this module, BMI was negatively connected to several genes encoding secreted proteins including GDF15, CCL3 and SPP1. Whatever the phase of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. CONCLUSION: network analyses confirm GDF15 as upregulated with calorie restriction-induced weight loss, concomitantly to macrophages markers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141221 | GEO | 2020/04/01

REPOSITORIES: GEO

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Project description:Background: Moderate weight loss can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of weight loss on the AT transcriptome is unknown. Objective: We investigated the global AT gene expression profile before and after two different rates of weight loss that resulted in similar total weight loss, and after a subsequent weight stabilization period. Design: In this randomized controlled trial, 25 male and 28 female individuals (BMI: 28-35 kg/m2) followed either a low-calorie diet (LCD; 1250 kcal/d) for 12 weeks or a very-low-calorie diet (VLCD; 500 kcal/d) for 5 weeks (weight loss (WL) period) and a subsequent weight stable (WS) period of four weeks. The WL period and WS period together is termed dietary intervention (DI) period. Abdominal subcutaneous AT biopsies were collected for microarray analysis, and gene expression changes were calculated for all three periods in the LCD group, VLCD group and between diets (ΔVLCD-ΔLCD). Results: Weight loss was similar between groups during the WL period (LCD: -8.1±0.5 kg, VLCD: -8.9±0.4 kg, difference p=0.25). Overall, more genes were significantly regulated and changes in gene expression were more extreme in the VLCD group compared to the LCD group. Gene sets related to mitochondrial function, adipogenesis and immunity/inflammation were more strongly upregulated on a VLCD compared to a LCD during the DI period (positive ΔVLCD-ΔLCD). Neuronal- and olfactory-related gene sets were decreased during the WL period and DI period in the VLCD group. Conclusions: The rate of weight loss (LCD vs. VLCD), with similar total weight loss, strongly regulates AT gene expression. Increased mitochondrial function and adipogenesis on a VLCD compared to a LCD reflect potential beneficial diet-induced changes in AT, while differential neuronal and olfactory regulation suggest functions of these genes beyond the current paradigm.

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Adipose tissue network analyses reveal negative association between GDF15 and BMI during weight management intervention.

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