Dataset Information

Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity.

ABSTRACT: OBJECTIVE:Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. This study compared muscle protein synthesis in adults with obesity and in lean controls in the fasted state and during an amino acid infusion. METHODS:Ten subjects with obesity (age: 36?±?3 years; BMI: 34?±?1 kg/m2 ) and ten controls (age: 35?±?3 years; BMI: 23?±?1 kg/m2 ) received an infusion of L-[2,3,3,4,5,5,5,6,6,6-2 H10 ]leucine (0.15 ?mol/kg fat-free mass/min) to measure muscle protein synthesis after an overnight fast and during amino acid infusion. RESULTS:Despite greater muscle mammalian target of rapamycin phosphorylation (P???0.05), fasted-state mixed-muscle and mitochondrial protein synthesis were lower in subjects with obesity (P???0.05). However, the change in mixed-muscle protein synthesis during the amino acid infusion was 2.7-fold greater in subjects with obesity (P???0.05), accompanied by a greater change in S6 kinase-1 phosphorylation (P???0.05). The change in mitochondrial protein synthesis did not differ between groups (P?>?0.05). CONCLUSIONS:Adults with obesity have reduced muscle protein synthesis in the fasted state, but this response is compensated for by a greater change in overall muscle protein synthesis during amino acid infusion.

SUBMITTER: Tran L

PROVIDER: S-EPMC6078204 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity.

Tran Lee L Kras Katon A KA Hoffman Nyssa N Ravichandran Jayachandran J Dickinson Jared M JM D'Lugos Andrew A Carroll Chad C CC Patel Shivam H SH Mandarino Lawrence J LJ Roust Lori L Katsanos Christos S CS

Obesity (Silver Spring, Md.) 20180612 7

<h4>Objective</h4>Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. This study compared muscle protein synthesis in adults with obesity and in lean controls in the fasted state and during an amino acid infusion.<h4>Methods</h4>Ten subjects with obesity (age: 36 ± 3 years; BMI: 34 ± 1 kg/m<sup>2</sup> ) and ten controls (age: 35 ± 3 years; BMI: 23 ± 1 kg/m<sup>2</sup> ) received an infusion of L-[2,3,3,4,5,5,5,6,6,6-<sup>2</sup> H<sub>10</sub> ]leucine (0.1 ...[more]

PMID: 29896930

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Project description:BackgroundPain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to suppress automatic or inappropriate responses, may be one such factor given previous research showing a relationship between higher PC and lower IC in non-migraine samples, and research showing reduced IC in migraine. Therefore, we examined whether lower IC interacts with increased PC to predict greater migraine severity as measured by pain intensity, attack frequency, and duration.MethodsWomen (n = 105) aged 18-50 years old (M = 38.0 ± 1.2) with overweight/obesity and migraine who were seeking behavioral treatment for weight loss and migraine reduction completed a 28-day smartphone-based headache diary assessing migraine headache severity. Participants then completed a modified computerized Stroop task as a measure of IC and self-report measures of PC (Pain Catastrophizing Scale [PCS]), anxiety, and depression. Linear regression was used to examine independent and joint associations of PC and IC with indices of migraine severity after controlling for age, body mass index (BMI) depression, and anxiety.ResultsParticipants on average had BMI of 35.1 ± 6.5 kg/m2and reported 5.3 ± 2.6 migraine attacks (8.3 ± 4.4 migraine days) over 28 days that produced moderate pain intensity (5.9 ± 1.4 out of 10) with duration of 20.0 ± 14.2 h. After adjusting for covariates, higher PCS total (β = .241, SE = .14, p = .03) and magnification subscale (β = .311, SE = .51, p < .01) scores were significant independent correlates of longer attack duration. IC interacted with total PCS (β = 1.106, SE = .001, p = .03) rumination (β = 1.098, SE = .001, p = .04), and helplessness (β = 1.026, SE = .001, p = .04) subscale scores to predict headache pain intensity, such that the association between PC and pain intensity became more positive at lower levels of IC.ConclusionsResults showed that lower IC interacted with higher PC, both overall and specific subcomponents, to predict higher pain intensity during migraine attacks. Future studies are needed to determine whether interventions to improve IC could lead to less painful migraine attacks via improvements in PC.

Project description:Maternal metabolic conditions are known risk factors for child autism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of child ASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72?hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019, 12: 1562-1573. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study investigated whether maternal obesity/diabetes and maternal circulating branched-chain amino acids (BCAAs) can jointly affect child ASD risk and whether the associations differ by child's sex. We found that the risk of ASD was greater among mothers with obesity/diabetes who also had elevated concentrations of BCAAs and that this risk was even greater for male children. These findings provide new evidence on fetal origins of ASD and sex difference and warrant additional investigation.

Dataset Information

Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity.

Publications

Lower Fasted-State but Greater Increase in Muscle Protein Synthesis in Response to Elevated Plasma Amino Acids in Obesity.

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