Elevated Plasma Branched-chain Amino Research Articles

Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE)

Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves’ disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12–24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.

Branched chain amino acids are associated with metabolic complications in liver transplant recipients

BackgroundObesity, dyslipidemia and type 2 diabetes (T2D) contribute substantially to increased cardiovascular morbidity and mortality in patients after orthotopic liver transplantation (OLTx). Elevated plasma branched chain amino acids (BCAA) are linked to metabolic disturbances and cardiovascular disease (CVD) risk profiles in several non-OLTx populations. MethodsCross-sectional analysis of liver transplant recipients from TransplantLines, a single-center biobank and cohort study. BCAA plasma levels were measured by means of nuclear-magnetic resonance spectroscopy. CVD and cardiometabolic factors were collected by using data from electronic patient records. Associations were determined between BCAA plasma levels and T2D, Metabolic Syndrome (MetS), CVD as well as mTOR inhibition in liver transplant recipients. Results336 Patients were divided into sex-stratified tertiles of total BCAA. MetS (P < 0.001) and T2D (P = 0.002) were significantly more frequent in subjects in the highest BCAA tertile. In logistic regression analyses, the multivariable adjusted odds ratio (OR) per 1 standard deviation increase in BCAA was 1.68 (95%CI: 1.18–2.20, P = 0.003) for MetS and 1.60 (95%CI: 1.14–2.23, P = 0.006) for T2D. Use of Sirolimus (mTOR inhibitor) was significantly associated with higher BCAA plasma levels, independent of age, sex, time after OLTx, MetS and other immunosuppressive medication (adjusted P = 0.002). ConclusionElevated BCAA plasma levels are associated with T2D, MetS and use of Sirolimus in liver transplant recipients. BCAA plasma levels may represent a valuable biomarker for cardiometabolic complications after OLTx.

A new caw of hepatic glycogen snthase deficiency. biochemical findings and comparison with reported cases

Hepatic glycogen synthase deficiency (GSD-0) is an autosomal recessive disorder first described in 1963. Fifteen cases in seven different families have been reported. Mutations in GYS2, the gene coding for liver glycogen synthase, were found in the four families studied. We report a new case of GSD-0 in a female patient born to healthy non-consanguineous French Canadian parents. She was referred for a family-history of hyperlipidemia at 7 years of age. In addition to increased plasma total cholesterol and triglyceride levels, workup revealed fasting hypoglycemia and ketonuria. Her only complaint was morning headaches. Growth and development were normal Physical exam including neurological exam was normal. Cerebral MRI and EEC were normal Biochemical findings consistent with the diagnosis included fasting hypoglycemia, ketonemia and hypoalaninemia, and postprandial hyperlactatemia and elevated plasma branched chain amino acid levels. Liver biopsy confirmed reduced glycogcn synthase activity. Ratio of active to inactive form of glycogen synthase was normal, suggesting reduced enzyme synthesis rather than synthesis of an inactive protein. Low hepatic glycogen content and mild to moderate liver stealosis were present. Plasma free carnitine concentrations decreased during fasting while esterified carnitine levels remained unchanged. In contrast to other cases, we twice observed an increase in blood glucose levels after administration of glucagon following 15 and 18 hours of fasting respectively (from 2.2 to 3.4 and 2.7 to 4.0 mmol/L respectively) Since her hepatic glycogen content was reduced, this might come from gluconcogenesis At 13 years of age, our patient still has fasting hypoglycemia although to a lesser degree. Her growth and intellectual development remain normal From our patient's clinical course and a review of the literature, we draw the following conclusions (1) non specific symptoms after overnight fasting were the presenting complaint in 6/16, 3 cases were brought to medical attention because of incidental findings, family history led to the diagnosis in 7 cases. (2) fasting hypoglycemia (16/16) and reduced liver glycogen content (8/8) are constant features, (3) other frequent biochemical findings include hyperlactatemia with feeding (13/16) and fasting hyperketonemia (9/16) and hypoalaninemia (8/16); (4) glucagon response after feeding is usually absent (4/6) but can be observed (2/6); (5) liver steatosis was observed in 5/8 cases. (6) growth and development are usually normal (12/16 and 13/16 respectively).