Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome

Abstract

Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions. Obesity is also considered to be primarily responsible for the rising prevalence of metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidemia, hypertension and hyperglycemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences. The current study was conducted in order to identify metabolic differences in visceral adipose tissue (VAT) collected from obese (body mass index 43-48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and nonobese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted VAT metabolomic profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerolphosphorylcholine, glycerolphosphorylethanolamine glycerolphosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic-vascular complications of obesity and may lead to the development of innovative targeted therapies.

Metabolic Syndrome, and Particularly the Hypertriglyceridemic-Waist Phenotype, Increases Breast Cancer Risk, and Adiponectin Is a Potential Mechanism: A Case–Control Study in Chinese Women

“…Currently, metabolic syndrome (MetS), a group of medical conditions that comprises obesity along with abnormal metabolic factors, including high blood pressure (BP), impaired fasting glucose (Glu), low high-density lipoprotein (HDL), and high triglycerides (TG) (12)(13)(14)(15), represents one of the most complex public health challenges. Metabolic syndrome is defined as the coexistence of several risk factors for cardiovascular diseases, diabetes, and certain cancers, such as endometrial cancer, prostate cancer, colorectal cancer, and breast cancer (16).…”

Gadolinium-based contrast agents: Stimulators of myeloid-induced renal fibrosis and major metabolic disruptors

“…Gadolinium-based contrast agent administration-a practice that has been inappropriately assumed to be biologically inconsequential-elevated kidney monoacylglycerols and diacylglycerols, such as stearoyl-arachidonoyl-glycerol (18:0/20:4)-a marker noted in viscerally-obese patients with the metabolic syndrome (Candi, Tesauro et al 2018). That all of these metabolites are altered in the same direction by gadolinium-based contrast agent administration and high fat diet-induced obesity, and that the combination often amplified the aberrancies (Figure 9) demonstrates a central and profound metabolic mediator of fibrosis by these two very different stimuli.…”

Ceramide and sphingosine 1-phosphate in adipose dysfunction

“…High content of DAG and ceramide, together with increased macrophage infiltration are found in subcutaneous adipose tissue of obese women with increased liver fat [125], suggesting that ceramide might also amplify chronic inflammation and insulin resistance in adipose tissue [125]. In addition, the levels of ceramides including C14:0, C16:0, C16:1 and C18:1 species are elevated in the white adipose tissue of obese and diabetic patients [106,124,126,127] and C16:0 and C18:0 ceramides levels are increased in adipose tissue of HFD-fed mice and are correlated with the development of adipocyte-specific insulin resistance [128]. The adipose tissue of C57BL mice on long-term HFD (16 or 18 weeks) also have increased C16:0 and C18:0 ceramide levels but decreased C24:0 ceramide [106,129].…”