Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss

Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss

Nicotinamide nucleotide transhydrogenase (NNT) mRNA expression is related to human obesity

If has been proposed that a spontaneous deletion in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7-11 in C57BL/6J (B6J) mice is associated with reduced glucose-stimulated insulin secretion in vitro, impaired glucose tolerance, higher epigonadal fat mass and altered susceptibility to diet induced obesity (DIO) of male B6J mice. A potential implication for NNT in human adipose tissue distribution has not been investigated so far. We therefore analyzed NNT mRNA expression in paired human samples of visceral (vis) and subcutaneous (sc) adipose tissue from 221 subjects with a wide range of BMI, insulin sensitivity and glucose tolerance. NNT mRNA expression is significantly higher in visceral fat of obese patients and correlates with body weight, BMI, % body fat, visceral and sc fat area, waist and hip circumference as well fasting plasma insulin. Multivariate linear regression analysis revealed visceral fat area, and % body fat, but not fasting plasma insulin and 2h OGTT glucose. In conclusion, our data suggest a functional relevance of NNT in the development of human obesity and visceral fat distribution

Biosignals reflect pair-dynamics in collaborative work : EDA and ECG study of pair-programming in a classroom environment

Collaboration is a complex phenomenon, where intersubjective dynamics can greatly affect the productive outcome. Evaluation of collaboration is thus of great interest, and can potentially help achieve better outcomes and performance. However, quantitative measurement of collaboration is difficult, because much of the interaction occurs in the intersubjective space between collaborators. Manual observation and/or self-reports are subjective, laborious, and have a poor temporal resolution. The problem is compounded in natural settings where task-activity and response-compliance cannot be controlled. Physiological signals provide an objective mean to quantify intersubjective rapport (as synchrony), but require novel methods to support broad deployment outside the lab. We studied 28 student dyads during a self-directed classroom pair-programming exercise. Sympathetic and parasympathetic nervous system activation was measured during task performance using electrodermal activity and electrocardiography. Results suggest that (a) we can isolate cognitive processes (mental workload) from confounding environmental effects, and (b) electrodermal signals show role-specific but correlated affective response profiles. We demonstrate the potential for social physiological compliance to quantify pair-work in natural settings, with no experimental manipulation of participants required. Our objective approach has a high temporal resolution, is scalable, non-intrusive, and robust.Peer reviewe

Identification of genetic loci associated with different responses to high-fat diet-induced obesity in C57BL/6N and C57BL/6J substrains

We have recently demonstrated that C57BL/6NTac and C57BL/6JRj substrains are significantly different in their response to high-fat diet-induced obesity (DIO). The C57BL/6JRj substrain seems to be protected from DIO and genetic differences between C57BL/6J and C57BL/6N substrains at 11 single nucleotide polymorphism (SNP) loci have been identified. To define genetic variants as well as differences in parameters of glucose homeostasis and insulin sensitivity between C57BL/6NTac and C57BL/6JRj substrains that may explain the different response to DIO, we analyzed 208 first backcross (BC1) hybrids of C57BL/6NTac and C57BL/6JRj [(C57BL/6NTac × C57BL/6JRj)F1 × C57BL/6NTac] mice. Body weight, epigonadal and subcutaneous fat mass, circulating leptin, as well as parameters of glucose metabolism were measured after 10 wk of high-fat diet (HFD). Genetic profiling of BC1 hybrids were performed using TaqMan SNP genotyping assays. Furthermore, to assess whether SNP polymorphisms could affect mRNA level, we carried out gene expression analysis in murine liver samples. Human subcutaneous adipose tissue was used to verify murine data of SNAP29. We identified four sex-specific variants that are associated with the extent of HFD-induced weight gain and fat depot mass. BC1 hybrids carrying the combination of risk or beneficial alleles exhibit the phenotypical extremes of the parental strains. Murine and human SC expression analysis revealed Snap29 as strongest candidate. Our data indicate an important role of these loci in responsiveness to HFD-induced obesity and suggest genes of the synaptic vesicle release system such as Snap29 being involved in the regulation of high-fat DIO

Nicotinamide nucleotide transhydrogenase (NNT) mRNA expression is related to human obesity

If has been proposed that a spontaneous deletion in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7-11 in C57BL/6J (B6J) mice is associated with reduced glucose-stimulated insulin secretion in vitro, impaired glucose tolerance, higher epigonadal fat mass and altered susceptibility to diet induced obesity (DIO) of male B6J mice. A potential implication for NNT in human adipose tissue distribution has not been investigated so far. We therefore analyzed NNT mRNA expression in paired human samples of visceral (vis) and subcutaneous (sc) adipose tissue from 221 subjects with a wide range of BMI, insulin sensitivity and glucose tolerance. NNT mRNA expression is significantly higher in visceral fat of obese patients and correlates with body weight, BMI, % body fat, visceral and sc fat area, waist and hip circumference as well fasting plasma insulin. Multivariate linear regression analysis revealed visceral fat area, and % body fat, but not fasting plasma insulin and 2h OGTT glucose. In conclusion, our data suggest a functional relevance of NNT in the development of human obesity and visceral fat distribution