Prospective analyses of white adipose tissue gene expression in relation to long-term body weight changes

Abstract

Background: Transcriptome analysis of abdominal subcutaneous white adipose tissue (sWAT) has identified important obesity-associated disturbances. However, the relation between sWAT transcriptome and long-term future changes in body weight remains elusive.

Objective: To investigate sWAT transcriptome signatures before and after long-term weight changes and assess their predictive value for body weight changes.

Design: A total of 56 women were followed longitudinally and subdivided into weight-stable (WS, n = 25), weight-gaining (WG, n = 14) and weight-losing (WL, n = 17) groups between baseline and follow-up (13 ± 1 years). The fasting sWAT transcriptome was analyzed by gene microarray at baseline and follow-up. Key genes associated with weight changes were validated using quantitative real-time PCR.

Results: In total 285 transcripts exhibited difference (FDR < 30%) in expression fold change over time between WL and WS women. WL women displayed decreased pro-inflammatory (NLRP3) but increased insulin-response gene (FASN and GLUT4) expression over time. In comparison, 461 transcripts displayed difference in expression fold change over time between WG and WS women (P < 0.05). Genes involved in autophagic processes (CDK5, SQSTM1 and FBXL2) were generally upregulated in WG women. At baseline, 307 and 302 transcripts were differentially expressed (FDR < 30%) in WL and WG women, respectively, when independently compared against WS women. Baseline expression of adipogenic and lipogenic genes (PPARG, IRS2 and HACD2) was lower, while pro-fibrotic (COL6A1) was higher, in WL than WS women; whereas protein processing genes were lower expressed in WG than in WS women.

Conclusion: In adult women, long-term body weight change associates with altered sWAT transcriptome. Expression of genes associated with inflammation, insulin response, adipogenesis and lipogenesis are linked to weight loss. However, other pathways such as autophagy not only associate but also predict future weight gain suggesting that intrinsic factors in sWAT impact tissue expansion.