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

Abstract

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.

Gene expression profile of subcutaneous adipose tissue in BMI-discordant monozygotic twin pairs unravels molecular and clinical changes associated with sub-types of obesity

“…8, 31 Studies also show that mitochondrial respiration in human fat cells is significantly reduced with increasing BMI. 32,33 Although the triggering events for the mitochondrial downregulation in obese fat are not known, it can be assumed that in energy overload, ATP production by cytosolic processes such as glycolysis are activated and mitochondria are needed less.…”

“…Similar findings have been reported in other studies. 31 Blood BCAA levels have been reported as increased, [34][35][36] and BCAA breakdown product alpha-ketoisocaproate as decreased along with decreased AT BCAA catabolism activity in obesity. 10 Unfortunately, our measured levels of valine, leucine and isoleucine did not show any significant differences between the Clusters, which could be because of lower statistical power owing to missing data for some of our twins.…”

Effects of Weight Loss on Glutathione Peroxidase 3 Serum Concentrations and Adipose Tissue Expression in Human Obesity

“…We therefore systematically studied abdominal visceral and SC AT GPX3 mRNA expression in parallel to GPX3 serum concentrations in a large cohort of individuals with a wide range of obesity, fat distribution and glucose metabolism / insulin sensitivity parameters. In addition, we included analyses of extreme obesity subphenotypes with IS compared to IR obesity [16] and a two-step bariatric surgery approach allowing to investigate changes in GPX3 AT expression (both SC and visceral depots) longitudinally [18, 35]. …”

Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes

“…Some models have been made for specific human tissue and cell types. For example, the white adipocyte model iAdipocyte1809 has been used to elucidate metabolic differences between lean and obese states (Mardinoglu et al, 2014, 2013) and before and after weight loss (Mardinoglu et al, 2015). However, we did not use iAdipocyte1809 or its successor iAdipocytes1850, because we wanted to be able to uncover brown adipocyte specific metabolic reactions.…”