OBJECTIVEWe investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity.RESEARCH DESIGN AND METHODSTwenty-two obese women followed a dietary intervention program composed of an energy restriction phase with a 4-week very-low-calorie diet and a weight stabilization period composed of a 2-month low-calorie diet followed by 3–4 months of a weight maintenance diet. At each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose tissue biopsies were performed. Adipose tissue gene expression profiling was performed using a DNA microarray in a subgroup of eight women. RT–quantitative PCR was used for determination of mRNA levels of 31 adipose tissue macrophage markers (n = 22).RESULTSBody weight, fat mass, and C-reactive protein level decreased and glucose disposal rate increased during the dietary intervention program. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were downregulated during energy restriction, upregulated during weight stabilization, and unchanged during the dietary intervention. The second comprised 511 mainly macrophage genes involved in inflammatory pathways that were not changed or upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. Accordingly, macrophage markers were upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. The increase in glucose disposal rates in each dietary phase was associated with variation in expression of sets of 80–110 genes that differed among energy restriction, weight stabilization, and dietary intervention.CONCLUSIONSAdipose tissue macrophages and adipocytes show distinct patterns of gene regulation and association with insulin sensitivity during the various phases of a dietary weight loss program.

Objective: Apelin is a novel adipokine acting on APJ receptor, regulated by insulin and tumor necrosis factor-a (TNF-a) in adipose tissue (AT). Plasma apelin levels are increased in obese hyperinsulinemic subjects. The aim was to investigate whether the hypocaloric diet associated with weight loss modifies the elevated plasma apelin levels and the expression of apelin and APJ receptor in AT in obese women. Design and methods: Fasting plasma levels of apelin and TNF-a as well as mRNA levels of apelin and APJ in AT were measured before and after a 12-week hypocaloric weight-reducing diet in 20 obese women (body mass index (BMI) before diet 32.2G6.4 kg/m 2 ). Twelve healthy women with a BMI of 20.7G 0.6 kg/m 2 served as reference. Results: Plasma levels of apelin and TNF-a were higher in obese compared with lean controls. The hypocaloric diet resulted in a significant decrease of BMI to 29.8G6.3 kg/m 2 , plasma insulin (8.16G 0.73 to 6.58G0.66 mU/l), apelin (369G25 pg/ml to 257G12 pg/ml), TNF-a levels (0.66G 0.04 pg/ml to 0.56G0.04 pg/ml), and AT mRNAs of apelin and APJ. In addition, changes in AT mRNA apelin were related to changes in AT mRNA APJ levels. Conclusion: The hypocaloric diet associated with weight loss reduces the increased plasma and AT expression of apelin in obese women. This reduced apelin expression in AT could contribute to decreased circulating apelin levels.European Journal of Endocrinology 158 905-910

ObjectiveCardiac natriuretic peptides (NPs) bind to two receptors (NPRA‐mediator of signaling; NPRC‐clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity.MethodsA cross‐sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12‐week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10).ResultsNPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P ≤ 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P ≤ 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARγ coactivator‐1α and uncoupling protein 1 (P ≤ 0.01).ConclusionsDecreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes.