Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance

Abstract

Background and Aims A novel bioactive peptide, mitochondrial‐derived peptide (MOTS‐c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS‐c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS‐c levels in obesity and explore the association between MOTS‐c levels and various metabolic parameters. Methods In this case‐control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017. Circulating MOTS‐c levels were measured, clinical data (eg, glucose, insulin, and lipid profile) were recorded, and anthropometric measurements were performed. Finally, we investigated correlations between MOTS‐c levels and related variables. Results MOTS‐c levels were significantly decreased in the obese group compared with the control group (472.61 ±22.83 vs 561.64 ±19.19 ng/mL, P <.01). After classification by sex, MOTS‐c levels were significantly decreased in obese male children and adolescents compared to their counterparts (465.26 ±24.53 vs 584.07 ±21.18 ng/mL, P <.001), while they were comparable between the obese and healthy female subjects (487.89 ±49.77 vs 508.85 ±38.76 ng/mL, P >.05). Further, MOTS‐c levels were negatively correlated with body mass index (BMI), BMI SD score, waist circumference, waist‐to‐hip ratio, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA‐IR), and glycated hemoglobin (HbA1c) in the male cohort. Conclusions Circulating MOTS‐c levels were decreased in obese male children and adolescents and correlated with markers of insulin resistance and obesity.

Development of a mass spectrometry based detection method for the mitochondrion‐derived peptide MOTS‐c in plasma samples for doping control purposes

“…In another recently published study, a commercially available ELISA was employed for the determination of endogenous plasma levels of young children and adolescents with obesity and yielded considerably higher levels of ca. 500 ng/mL …”

“…Considering preventive anti‐doping research demands, it was the aim to cover structurally related peptides of potential performance‐enhancing properties. In the literature, endogenous MOTS‐c levels vary from 154 pg/mL to 584 ng/mL . The presented LC/MS‐based detection method was validated with a LLOD of 100 pg/mL and should therefore be capable of detecting endogenous MOTS‐c plasma levels.…”

“…100 pg/mL. Despite the fact that endogenous levels of hMOTS in human plasma were reported to be 200 pg/mL or below, reaching up to approximately 500 ng/mL, attempts to detect MOTS‐c in authentic plasma samples from healthy volunteers by LC/MS failed. Consequently, further studies are warranted especially if the peptide (or its synthetic analogs) is considered for clinical development.…”

“…Plasma samples of 20 healthy individuals (10 male +10 female donors) were used to test for endogenous MOTS‐c concentrations. The samples were frozen as aliquots and tested in parallel utilizing the MS‐based approach and a commercially available competitive ELISA kit (Cloud‐Clone Corp., CEX132Hu) used in previous studies . Regarding the latter, all steps of the sample preparation and analysis were conducted in accordance with the manufacturer's protocol.…”

MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

“…It is possible that the exported MOTS‐c transcript may be cotranslated and translocated to the mitochondria using such mitochondrial‐associated cytoplasmic ribosomes. Work is also in progress to understand cellular cues that induce MOTS‐c expression, and metabolic alterations and inflammation may be key. Similar to HN, MOTS‐c has both intracellular and endocrine roles .…”