Plasma Palmitoyl-Carnitine (AC16:0) Is a Marker of Increased Postprandial Nonesterified Incomplete Fatty Acid Oxidation Rate in Adults With Type 2 Diabetes

Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity

“…Interestingly, a limited effect on the concentration of acylcarnitines was measured in HFD-treated mice even without significantly affecting glucose uptake. Our findings are in line with previous studies in which in insulin-resistant subjects, glucose-stimulated insulin release was not able to adequately suppress longchain acylcarnitine production in muscles, and its plasma concentration remained high during insulin clamp or a standard meal (11,21). Thus, measurements of plasma long-chain acylcarnitine levels during glucose tolerance and insulin clamp are suitable to evaluate insulin sensitivity in muscle and the heart.…”

“…Because longchain FAs are the main energy substrates in the skeletal muscles and the heart, these tissues are considered essential contributors to the long-chain acylcarnitine pool in plasma (16,17). Increased plasma levels of various acylcarnitines were found in experimental animal models of insulin resistance (16) and in patients with obesity, impaired glucose tolerance and type 2 diabetes (11,(18)(19)(20)(21)(22). However, previous studies did not evaluate the tissue-specific impairment of insulin action and reported inconclusive associations of plasma acylcarnitine levels with glucose disposal.…”

Integrated biomarker for type 2 diabetes mellitus and impaired fasting glucose based on metabolomics analysis using ultra‐high performance liquid chromatography quadrupole‐Orbitrap high‐resolution accurate mass spectrometry

“…For example, the L‐lysine, choline, L‐proline, L‐valine, L‐isoleucine and LysoPC (16:1) metabolites were increased, while the LysoPC (P‐16:0) and LysoPC (P‐18:0) metabolites decreased, which was also consistent with previous reports 11,26,34 . Furthermore, the studies suggested that the levels of acetyl‐L‐carnitine, 2‐methylbutyryl‐carnitine and palmitoyl‐carnitine were positively correlated with T2DM, 35,36 which was confirmed in this study.…”

Loss of Muscle Carnitine Palmitoyltransferase 2 Prevents Diet-Induced Obesity and Insulin Resistance despite Long-Chain Acylcarnitine Accumulation

“…Interest in studying non-canonical, lipotoxic roles for ACs has largely arisen from an increasing number of reports that observe differences in LCACs during numerous stresses, including fasting, ketogenic diet, exercise, overnutrition, heart disease, and insulin resistance ( Adams et al, 2009 ; Bouchouirab et al, 2018 ; Mai et al, 2013 ; McCoin et al, 2015a ; Sampey et al, 2012 ; Schooneman et al, 2013 , 2014 ; Soeters et al, 2009 ; Su et al, 2005 ; Xu et al, 2016 ; Zhang et al, 2017 ). LCACs are accused of interfering with insulin signaling ( Adams et al, 2009 ; Aguer et al, 2015 ; Bouchouirab et al, 2018 ; Keung et al, 2013 ; Kim et al, 2014 ; Koves et al, 2008 ; Li et al, 2015 ; Liepinsh et al, 2016 , 2017 ; Mai et al, 2013 ; McCoin et al, 2015b ; Power et al, 2007 ; Ringseis et al, 2012 ; Samimi et al, 2016 ; Vavrova et al, 2016 ; Warfel et al, 2017 ), and they accumulate at particularly high levels in the skeletal muscle, compared with other tissues ( Pradas et al, 2018 ). However, the lack of mouse models with consistent and specific increases in endogenously generated muscle LCACs has hampered the assessment of their biological effects.…”

“…Among potential metabolic disruptors are medium-chain acylcarnitines (MCACs) and long-chain acylcarnitines (LCACs), fatty acid oxidative intermediates that when accumulate are implicated as causative in insulin resistance ( Adams et al, 2009 ; Aguer et al, 2015 ; Bouchouirab et al, 2018 ; Keung et al, 2013 ; Kim et al, 2014 ; Koves et al, 2008 ; Li et al, 2015 ; Liepinsh et al, 2016 , 2017 ; Mai et al, 2013 ; McCoin et al, 2015b ; Power et al, 2007 ; Ringseis et al, 2012 ; Samimi et al, 2016 ; Vavrova et al, 2016 ; Warfel et al, 2017 ). LCACs accumulate during numerous physiological and non-physiological stresses, including fasting, ketogenic diet, exercise, overnutrition, heart disease, and insulin resistance ( Adams et al, 2009 ; Bouchouirab et al, 2018 ; Mai et al, 2013 ; McCoin et al, 2015a ; Sampey et al, 2012 ; Schooneman et al, 2013 , 2014 ; Soeters et al, 2009 ; Su et al, 2005 ; Xu et al, 2016 ; Zhang et al, 2017 ). We previously demonstrated a high degree of LCAC accumulation in a mouse model of heart and muscle carnitine palmitoyltransferase 2 (CPT2) deficiency ( Cpt2 M −/− ) ( Pereyra et al, 2017 ).…”