Switch from stress response to homeobox transcription factors in Adipose tissue after profound fat loss

Background In obesity, impaired adipose tissue function may promote secondary disease through ectopic lipid accumulation and excess release of adipokines, resulting in systemic low-grade inflammation, insulin resistance and organ dysfunction. However, several of the genes regulating adipose tissue function in obesity are yet to be identified. Methodology/Principal Findings In order to identify novel candidate genes that may regulate adipose tissue function, we analyzed global gene expression in abdominal subcutaneous adipose tissue before and one year after bariatric surgery (biliopancreatic diversion with duodenal switch, BPD/DS) (n = 16). Adipose tissue from lean healthy individuals was also analyzed (n = 13). Two different microarray platforms (AB 1700 and Illumina) were used to measure the differential gene expression, and the results were further validated by qPCR. Surgery reduced BMI from 53.3 to 33.1 kg/m2. The majority of differentially expressed genes were down-regulated after profound fat loss, including transcription factors involved in stress response, inflammation, and immune cell function (e.g., FOS, JUN, ETS, C/EBPB, C/EBPD). Interestingly, a distinct set of genes was up-regulated after fat loss, including homeobox transcription factors (IRX3, IRX5, HOXA5, HOXA9, HOXB5, HOXC6, EMX2, PRRX1) and extracellular matrix structural proteins (COL1A1, COL1A2, COL3A1, COL5A1, COL6A3). Conclusions/Significance The data demonstrate a marked switch of transcription factors in adipose tissue after profound fat loss, providing new molecular insight into a dichotomy between stress response and metabolically favorable tissue development. Our findings implicate homeobox transcription factors as important regulators of adipose tissue function

Mutation models for DVI analysis

In recent years, the use of DNA data for personal identification has become a crucial feature for forensic applications such as disaster victim identification (DVI). Computational methods to cope with these kinds of problems must be designed to handle large scale events with a high number of victims, obtaining likelihood ratios and posterior odds with respect to different identification hypotheses. Trying to minimize identification error rates (i.e., false negatives and false positives), a number of computational methods, based either on the choice between alternative mutation models or on the adoption of a different strategy, are proposed and evaluated. Using simulation of DNA profiles, our goal is to suggest which is the most appropriate way to address likelihood ratio computation in DVI cases, especially to be able to efficiently deal with complicating issues such as mutations or null alleles, considering that data about these latter are limited and fragmentary. ?? 2014 Elsevier Ireland Ltd

Patient characteristics at inclusion and after bariatric surgery.

<p>Patient characteristics at inclusion and after bariatric surgery.</p

Circulating levels of kynurenines, neopterin and B vitamins at inclusion of patients undergoing bariatric surgery.

<p>Circulating levels of kynurenines, neopterin and B vitamins at inclusion of patients undergoing bariatric surgery.</p

The kynurenine pathway of tryptophan metabolism.

<p>IDO, indoleamine 2,3-dioxygenase; TDO, tryptophan 2,3-dioxygenase; KAT, kynurenine aminotransaminase; KMO, kynurenine 3-monooxygenase; KYNU, kynureninase; 3OH-kynurenine, 3-hydroxy kynurenine; 3OH-anthranilic acid, 3-hydroxy anthranilic acid; B6, vitamin B6 (pyridoxal 5`-phosphate); B2, vitamin B2 (flavin adenine dinucleotide).</p

Inflammatory markers after bariatric surgery.

<p>Samples were measured at baseline, 3 months and after one year in 37 patients undergoing bariatric surgery. <i>P</i> values for trend over time are estimated with a random intercept mixed model, adjusted for type of operation and vitamin B supplementation. Data are given as median (25th to 27th percentile).</p

Correlations of fasting glucose, HbA1c and the triglyceride:HDL ratio with tryoptophan, kynurenine and the kynurenine metabolites, inflammatory markers, vitamin B6 and vitamin B3 at baseline.

<p>Regression coefficient based on Spearman rank correlation test, corrected for age, gender and eGFR, are shown in the figure. Tg, triglyceride; HDL, high density lipoprotein; Trp, tryptophan; Kyn, kynurenine; KA kynurenic acid; AA, anthranilic acid; HK, 3-hydroxy kynurenine; XA, xanthurenic acid; HAA, 3-hydroxy anthranilic acid; QA, quinolinic acid; KTR, kynurenine:tryptophan ratio; PLP, pyridoxal 5`-phosphate. *p-value < 0.05; **p-value < 0.005.</p

Circulating levels of tryptophan, kynurenines and B vitamins before and after bariatric surgery.

<p>Circulating levels of tryptophan, kynurenines and B vitamins before and after bariatric surgery.</p