Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization.

Abstract Objective- We investigated the regulation of adipose tissue (AT) gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity. Research Design and Methods- 22 obese women followed a dietary intervention program (DI) composed of an energy restriction phase (ER) with 4-week very-low-calorie diet and a weight stabilization period (WS) composed of 2-month low-calorie diet followed by 3-4 months of weight maintenance diet. At each time point, euglycemic hyperinsulinemic clamp and subcutaneous AT biopsies were performed. AT gene expression profiling was performed using DNA microarray in a subgroup of 8 women. Reverse transcription-qPCR was used for determination of mRNA levels of 31 AT macrophage markers (n=22). Results- Body weight, fat mass and C-reactive protein level decreased and glucose disposal rate increased during DI. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were down-regulated during ER, up-regulated during WS and unchanged during DI. The second comprised 511 mainly macrophage genes involved in inflammatory pathways that were not changed or up-regulated during ER and down-regulated during WS and DI. Accordingly, macrophage markers were up-regulated during ER and down-regulated during WS and DI. The increase in glucose disposal rate in each dietary phase was associated with variation in expression of sets of 80 to 110 genes that differed between ER, WS and DI. Conclusions- AT macrophages and adipocytes show distinct patterns of gene regulation and association with insulin sensitivity during the various phases of a dietary weight loss program.