Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Abstract

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/ mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome. Keywords Obesity • Metabolomics • Body mass index • Metabolic syndrome • Branched chain amino acids • Histidine • Tryptophan • Adipose tissue Abbreviations BMI Body mass index HDL High-density lipoprotein GC/MS Gas chromatography/mass spectrometry LC/MS/MS Liquid chromatography/mass spectrometry RF Random forest analysis Handling editor: K. Barnouin. M. C. Piro and M. Tesauro are co-first authors.

Circulating amino acids as fingerprints of visceral adipose tissue independent of insulin resistance: a targeted metabolomic research in women

“…While many studies have assessed specific plasma metabolite alterations in obesity, few have focused on biomarkers specific for visceral adipose tissue and have aimed to identify AAs associated with visceral fat [10,16,[20][21][22][23]. In a sample of 59 women (lean, overweight, and obese), Boulet et al [21] showed that total AAs and branchedchain AAs were associated with visceral adipose tissue.…”

“…The emergence of metabolomics has allowed the identification of biomarkers associated with obesity as well as biomarkers predictive of obesity-associated metabolic disorders and has provided useful information on the molecular pathways of this disease [7][8][9]. Because amino acids (AAs) act as both metabolic modulators and substrates for the synthesis of proteins, they have been extensively studied in obesity both in observational and interventional studies [10]. Observational studies on the metabolomic changes associated with obesity and obesity-associated insulin resistance have found increased levels of AAs including branched-chained AAs (valine, leucine, and isoleucine) [11][12][13].…”

“…Furthermore, it has been shown that weight loss induced by either hypocaloric diets or bariatric surgery leads to lower levels of these AAs [14,15]. Although a growing number of studies has tried to identify biomarkers associated with obesity, few have investigated AAs associated with visceral adiposity, and many have used histological samples of adipose tissue and evaluated the metabolome within adipose tissue, without concentrating on biomarkers easily accessible in clinical practice [10,16]. Given the fact that identified AAs associated with visceral adiposity were also linked to insulin resistance, in this study we aimed to investigate, in healthy subjects, specific changes in AA levels as the fingerprint of increased visceral adiposity independent of insulin resistance.…”

Association of Gut Hormones and Microbiota with Vascular Dysfunction in Obesity

“…Moreover, the chronic accumulation of fat leads to the deregulation of energetic storage homeostasis that in turn increase the circulating levels of saturated fatty acid and then glucose and lipids blood levels [5,6]. These events chronically lead to classical complications of obesity, which are dyslipidemia, cardiovascular disease, hypertension, atherosclerosis, and diabetes mellitus (T2DM) [7].…”

Health-related quality of life in patients with advanced colorectal cancer: a predictive nomogram including BMI, sex and age

“…Obesity is a complex physiopathological state that involves significant changes in the systemic metabolic profile (18,19), circulating levels of insulin and other growth hormones (20), baseline innate immunity activation (21) and vasomotor response (22)(23)(24). Such changes pave the way for an increase in the risk of cardiovascular diseases, cancer and diabetes (25)(26)(27).…”