Diversity in levels of intracellular total creatine and  triglycerides in human skeletal muscles observed by<sup>1</sup>H-MRS

Rico-Sanz, J.; Thomas, E. Louise; Jenkinson, G. M.; Mierisová, Šárka; Iles, Richard A.; Bell, Jimmy D.

doi:10.1152/jappl.1999.87.6.2068

Cited by 86 publications

(90 citation statements)

References 36 publications

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“…Muscle spectra were obtained from the soleus (S-IMCL) and tibialis (T-IMCL) (TR 1500ms, TE 135ms, 256 averages). IMCL was determined relative to total muscle creatine signal after correcting for T 1 and T 2 (18).…”

Section: Methodsmentioning

confidence: 99%

Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

et al. 2011

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Our investigation addresses the hypothesis that disruption of third trimester development by preterm birth alters multiple biological pathways affecting metabolic health in adult life. We compared healthy adult volunteers aged 18 -27 y born at Յ33 wk gestation or at term. We used whole-body MRI, 1 H magnetic resonance spectroscopy (MRS) of liver and muscle, metabonomic profiling of blood and urine, and anthropometric and blood pressure measurements. Preterm subjects had greater (mean difference (95% CI)) total [2.21 L (0.3, 4.1), p ϭ 0.03] and abdominal adipose tissue [internal 0.51 (0.1, 0.9), p ϭ 0.007]; blood pressure [systolic 6.5 mm Hg (2.2, 10.8), p ϭ 0.004; diastolic 5.9 (1.8, 10.1), p ϭ 0.006]; and ectopic lipid (ratio (95% CI)), intrahepatocellular lipid (IHCL) 3.01 (1.78, 5.28) p Ͻ 0.001, and tibialis-intramyocellular lipid (T-IMCL) [1.31 (1.02, 1.69) p ϭ 0.04]. In preterm, compared with term men, there was greater internal adipose tissue [mean (SD); men: preterm 4.0 (1.6), term 2.7 (1.1) liters; women: preterm 2.6 (0.9); term 2.6 (0.5); gender-gestation interaction p ϭ 0.048] and significant differences in the urinary metabolome (elevated methylamines and acetylglycoproteins, lower hippurate). We have identified multiple premorbid biomarkers in ex-preterm young adults, which are most marked in men and indicative of risks to later wellbeing. These data offer insight into biological trajectories affected by preterm birth and/or neonatal care. A round 2% of births in the developed world are below 33 wk gestation. This rate is rising as is survival and Ͼ90% of these infants will go home. Survival free of major impairment is also rising, bringing with it the expectation of life-long health. Preterm birth may be a risk to adult health (1,2). Several groups describe higher blood pressure (3-7). Insulin resistance (8) and poorer reproductive health (9) have also been reported. The biological mediators are unknown.We have previously shown that by term, preterm infants have an altered body composition with significantly greater abdominal adipose tissue (10) and intrahepatocellular lipid (IHCL) (11). There is a high degree of correlation between hypertension, insulin resistance, and abdominal obesity. Abdominal adipose tissue in particular seems to play a major role in the pathogenesis of the metabolic syndrome (12). Increased "ectopic" lipid in liver and muscle as IHCL and soleus and tibialis intramyocellular lipid (S-IMCL and T-IMCL) are also strongly associated with these conditions (13).In this proof-of-concept study, we postulated that disruption of the normal pattern of third trimester development by preterm birth will affect a range of systems affecting metabolic health. We tested the primary hypothesis that young adults born at or below 33 wk gestation would have increased abdominal adiposity in the absence of overt obesity. We also evaluated IHCL, IMCL, fasting glucose and insulin, insulin resistance, serum lipids and serum, and urine metabolomes. METHODSApproval for the study was obtained fro...

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Section: Methodsmentioning

confidence: 99%

Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

et al. 2011

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“…IHCL and IMCL were measured by 1 H-MRS within 1 week of the metabolic study and prior to the start of the exercise programme [22,23] as detailed in ESM 1. Subjects were asked not to exercise for 72 h prior to the measurement.…”

Section: Methodsmentioning

confidence: 99%

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

et al. 2006

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Aims/hypothesis It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. Subjects and methods We randomised 17 sedentary overweight male subjects (age 50±2.6 years, BMI 27.6±0.5 kg/ m 2 ) to a 6-week exercise programme (n=10) or control group (n=7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg −1 min −1 ]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. Results After 6 weeks, fasting glycerol, palmitic acid Ra (p=0.003, p=0.042) and NEFA concentration (p=0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p=0.026; p=0.007 and p=0.04). There was no change in muscle triacylglycerol and liver fat in either group. Conclusions/interpretation Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.

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“…Peak positions and areas of interest [phosphocreatine (PCr), inorganic free phosphate (Pi), ␤-ATP (3 peaks), ␣-ATP (2 peaks), ␥-ATP (2 peaks), and phosphomonoester] were determined by time domain fitting using jMRUi (30,57) utilizing AMARES (A Method of Accurate, Robust and Efficient Spectral fitting), a nonlinear leastsquare-fitting algorithm using previously built prior-knowledge files (49). All exercise spectra were corrected for saturation using the fully relaxed spectra for that day.…”

Section: Spectroscopy Analysismentioning

confidence: 99%

Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids

Cree-Green

Newcomer

Coe

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Cree-Green M, Newcomer BR, Coe G, Newnes L, Baumgartner A, Brown MS, Pyle L, Reusch JE, Nadeau KJ. Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids. 31 phosphorus MR spectroscopy before, during, and after near-maximal isometric calf exercise, and peripheral IR was assessed with an 80 mU·m Ϫ2 ·min Ϫ1 hyperinsulinemic euglycemic clamp. Girls with HAS had higher androgens [free androgen index 7.9(6.6,15.5) vs. 3.5(3.0,4.0), P Ͻ 0.01] and more IR [glucose infusion rate 9.4(7.0, 12,2) vs. 14.5(13.2,15.8) mg·kg lean Ϫ1 ·min Ϫ1 , P Ͻ 0.01]. HAS girls also had increased markers of inflammation including CRP, platelets, and white blood cell count and higher serum free fatty acids during hyperinsulinemia. Mitochondrial oxidative phosphorylation was lower in HAS [0.11(0.06,0.19) vs. 0.18(0.12,0.23) mmol/s, P Ͻ 0.05], although other spectroscopy markers of mitochondrial function were similar between groups. In multivariate analysis of the entire cohort, IR related to androgens, oxidative phosphorylation, and free fatty acid concentrations during hyperinsulinemia. These relationships were present in just the HAS cohort as well. Obese girls with HAS have significant peripheral IR, which is related to elevated androgens and free fatty acids and decreased mitochondrial oxidative phosphorylation. These may provide future options as targets for therapeutic intervention.hyperandrogenism; insulin resistance; mitochondria; obesity; hyperandrogenic syndrome HYPERANDROGENIC SYNDROME (HAS), also known as polycystic ovarian syndrome (PCOS), affects at least 10 -15% of the female population in the United States, with a recent increase in prevalence associated with rising obesity rates (32). Women with HAS have a three-to fourfold increased risk of developing type 2 diabetes (T2D) compared with BMI-matched controls (37, 58). This increased risk is thought to be secondary to long-standing insulin resistance (IR) (37). There is also evidence of IR in youth with HAS (2). Similar to findings in T2D, peripheral IR as assessed with a hyperinsulinemic euglycemic clamp has been well documented in adults with HAS (7, 15), with similar but fewer data in youth (2). However, the mechanism of IR in HAS remains uncertain, and as a result the best treatments for HAS are also unclear.A leading theory explaining IR in T2D includes defects in mitochondrial function in combination with excess serum free fatty acids (FFA), which can cause alterations in intracellular insulin signaling (52). Other potential mechanisms involve altered fat metabolism and inflammation, which have been documented in T2D and HAS but have not been examined in adolescents with HAS (14,25,29,33,54). However, data examining the role of mitochondria in IR in HAS are limited and conflicting. Muscle mitochondrial oxidation gene expression for oxidative enzymes such as citrate synthase, or ␤-hydroxyacyl-CoA dehydrogenase were similar between women with and without HAS despite worse IR in the wom...

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Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by¹H-MRS

Cited by 86 publications

References 36 publications

Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids

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Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by1H-MRS

Cited by 86 publications

References 36 publications

Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

Peripheral insulin resistance in obese girls with hyperandrogenism is related to oxidative phosphorylation and elevated serum free fatty acids

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Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by¹H-MRS