K Sreekumaran Nair

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (256)1499.45 Total impact

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    ABSTRACT: The notion that mitochondria contribute to obesity-induced insulin resistance is highly debated. Therefore, we determined if obese (BMI=33 kg/m(2)), insulin-resistant women with polycystic ovary syndrome had aberrant skeletal muscle mitochondrial physiology compared to lean, insulin-sensitive women (BMI=23 kg/m(2)). Maximal whole-body and mitochondrial oxygen consumption were not different between obese and lean women. However, obese women exhibited lower mitochondrial coupling and phosphorylation efficiency and elevated mitochondrial H2O2 (mtH2O2) emissions compared to lean women. We further evaluated the impact of 12-weeks of aerobic exercise on obesity-related impairments in insulin sensitivity and mitochondrial energetics in the fasted state and following a high-fat, mixed meal. Exercise training reversed obesity-related mitochondrial derangements as evidenced by enhanced mitochondrial bioenergetics efficiency and decreased mtH2O2 production. A concomitant increase in catalase antioxidant activity and decreased DNA oxidative damage indicate improved cellular redox status and a potential mechanism contributing to improved insulin sensitivity. mtH2O2 emissions were refractory to a high-fat meal at baseline but after exercise mtH2O2 emissions increased following the meal, which resembles previous findings in lean individuals. We demonstrate obese women exhibit impaired mitochondrial bioenergetics in the form of decreased efficiency and impaired mtH2O2 emissions, while exercise effectively restores mitochondrial physiology toward that of lean, insulin-sensitive individuals. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 01/2015; · 7.90 Impact Factor
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    ABSTRACT: Context: Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity (OXPHOS). Objective: The primary objective was to determine whether eight weeks of combined training (CT) has more robust effect than, endurance training (ET) or resistance training (RT) on mitochondrial physiology in healthy young (18-30 y) and older (≥65 y) adults. Intervention: Thirty-four young and 31 older adults were randomized to eight weeks of ET, RT, control/CT. Control subjects completed eight weeks of no exercise (control) followed by eight weeks of CT. Body composition, skeletal muscle strength, and peak oxygen uptake were measured before and after the intervention. Vastus lateralis muscle biopsies were obtained before and 48 h after the intervention. Mitochondrial physiology was evaluated by high-resolution respirometry, and expression of mitochondrial proteins and transcription factors by quantitative PCR and immunoblotting. Results: ET and CT significantly increased oxidative capacity and expression of mitochondrial proteins and transcription factors. All training modalities improved body composition, cardiorespiratory fitness, and skeletal muscle strength. CT induced the most robust improvements in mitochondrial related outcomes and physical characteristics despite lower training volumes for the ET and RT components. Importantly, most of the adaptations to training occurred independent of age. Conclusion: Collectively, these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity. Although CT induced the most robust improvements in the outcomes measured. In conclusion, CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age.
    The Journal of clinical endocrinology and metabolism. 01/2015;
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    ABSTRACT: Acute aerobic exercise increases reactive oxygen species and could potentially damage proteins, but exercise training (ET) enhances mitochondrial respiration irrespective of age. Here, we report a differential impact of ET on protein quality in young and older participants. Using mass spectrometry we measured oxidative damage to skeletal muscle proteins before and after 8 weeks of ET and find that young but not older participants reduced oxidative damage to both total skeletal muscle and mitochondrial proteins. Young participants showed higher total and mitochondrial derived semitryptic peptides and 26S proteasome activity indicating increased protein degradation. ET however, increased the activity of the endogenous antioxidants in older participants. ET also increased skeletal muscle content of the mitochondrial deacetylase SIRT3 in both groups. A reduction in the acetylation of isocitrate dehydrogenase 2 was observed following ET that may counteract the effect of acute oxidative stress. In conclusion aging is associated with an inability to improve skeletal muscle and mitochondrial protein quality in response to ET by increasing degradation of damaged proteins. ET does however increase muscle and mitochondrial antioxidant capacity in older individuals, which provides increased buffering from the acute oxidative effects of exercise. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 12/2014; · 4.31 Impact Factor
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    ABSTRACT: Maintenance of musculoskeletal function in older adults is critically important for preserving cardiorespiratory function and health span. Aerobic endurance training (ET) improves skeletal muscle metabolic function including age-related declines in muscle mitochondrial function. To further understand the underlying mechanism of enhanced muscle function with ET, we profiled the gene transcription (mRNA levels) patterns by gene array and determined the canonical pathways associated with skeletal muscle aging in a cross-sectional study involving vastus lateralis muscle biopsy samples of four subgroups (young and old, trained, and untrained). We first analyzed the sedentary individuals and then sought to identify the pathways impacted by long-term ET (>4 years) and determined the age effect. We found that skeletal muscle aging in older sedentary adults decreased mitochondrial genes and pathways involved in oxidative phosphorylation while elevating pathways in redox homeostasis. In older adults compared to their younger counterparts who chronically perform ET however, those differences were absent. ET did, however, impact nearly twice as many genes in younger compared to older participants including downregulation of gene transcripts involved in protein ubiquitination and the ERK/MAPK pathways. This study demonstrates that in individuals who are chronically endurance trained, the transcriptional profile is normalized for mitochondrial genes but aging impacts the number of genes that respond to ET including many involved in protein homeostasis and cellular stress.
    Physiological Reports. 12/2014; 2(12).
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    ABSTRACT: We, as representatives of scientific organizations devoted to improving health care and advancing research, reaffirm that it is the mission of our respective medical journals to report and disseminate data from scientific investigation, evolving medical care, and innovative treatments. We believe these reports serve to unite basic scientists, clinical investigators, and medical professionals regardless of their country of origin, ethnic group, or political leaning. We believe that these efforts achieve the common goal of advancing scientific discoveries that lead to improved health of people worldwide. On the basis of our goals and principles, our respective journals will refrain from publishing articles addressing political issues that are outside of either research funding or health care delivery.
    Endocrine Practice 10/2014; · 2.59 Impact Factor
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    ABSTRACT: We determined the effect of hyperandrogenemia as observed in polycystic ovary syndrome (PCOS) on fasting and glucose-stimulated proatherogenic inflammation markers in lean healthy reproductive-age women. Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n=8 each) for 5 days. Interleukin-6 (IL-6) mRNA and IL-6 release from mononuclear cells (MNC), plasma IL-6 and C-reactive protein (CRP), and MNC-derived (matrix metalloproteinase-2) MMP-2 protein were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment. Before treatment, subjects receiving dehydroepinadrosterone (DHEA) or placebo exhibited no differences in androgens, or any proatherogenic inflammation markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate (DHEA-S), and increased the percent change from baseline in fasting IL-6 mRNA, IL-6 release, plasma IL-6, and CRP and MMP-2 protein. However, there were no differences in any of the proatherogenic inflammation markers following glucose ingestion after DHEA administration. We conclude that in lean reproductive-age women, proatherogenic inflammation in the fasting state increases after raising circulating androgens to levels observed in PCOS. However, this hyperandrogenemia-induced MNC activation does not provoke a similar response to subsequent glucose ingestion.
    Hormone and Metabolic Research 09/2014; · 2.04 Impact Factor
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    ABSTRACT: Context: Insulin and essential amino acids (EAA) regulate skeletal muscle protein synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and oxidative function remain to be clearly defined. Objective: Determine the effects of high or low insulin with or without EAA on MiPS. Design: Thirty participants were randomized to three groups of 10 each with each participant studied twice. Study groups comprised of 1) Low and High Insulin 2) Low Insulin with and without EAA or 3) High Insulin with and without EAA. Setting: In-patient Clinical Research Unit. Participants: Eligibility included 18-45 years old, BMI<25 kg/m(2) and free of diseases and medications that may impair mitochondrial function. Intervention: Low (∾6 μ U/mL) and high (∾40 μ U/mL) insulin levels were maintained by intravenous insulin infusion during a somatostatin clamp while maintaining euglycemia (4.7-5.2 mM) and replacing growth hormone and glucagon. EAA infusion was 5.4% Nephramine. L-[ring(13)C6]-phenylalanine was infused and muscle needle biopsies were performed. Main Outcomes: Muscle MiPS, oxidative enzymes and plasma amino acid metabolites. Results: MiPS and oxidative enzyme activities did not differ between low and high insulin (MiPS: 0.07±0.009 vs. 0.07±0.006%/hr p=0.86) or between EAA and saline during low insulin (MiPS: 0.05±0.01 vs. 0.07±0.01 p=0.5). During high insulin, EAA in comparison with saline increased MiPS (0.1±0.01 vs. 0.06±0.01 p<0.05) and cytochrome-c-oxidase activity (p<0.05) but not citrate synthase (p=0.27). EAA infusion decreased (p<0.05) glucose infusion rates needed to maintain euglycemia during low (∾40%) and high insulin (∾24%). Conclusion: EAA increased MiPS and oxidative enzyme activity only with high insulin concentrations.
    Journal of Clinical Endocrinology &amp Metabolism 09/2014; · 6.31 Impact Factor
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    ABSTRACT: Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth.
    PLoS ONE 07/2014; 9(7):e102031. · 3.53 Impact Factor
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    ABSTRACT: Background and Aims Amino acid (AA) availability is critical to maintain protein homeostasis and reduced protein intake causes a decline in protein synthesis. Citrulline, an amino acid metabolite, has been reported to stimulate muscle protein synthesis in malnourished rats. Methods To determine whether citrulline stimulates muscle protein synthesis in healthy adults while on a low-protein diet, we studied 8 healthy participants twice in a cross-over study design. Following a 3-days of low-protein intake, either citrulline or a non-essential AA mixture (NEAA) was given orally as small boluses over the course of 8 hours. [ring-13C6] phenylalanine and [15N] tyrosine were administered as tracers to assess protein metabolism. Fractional synthesis rates (FSR) of muscle proteins were measured using phenylalanine enrichment in muscle tissue fluid as the precursor pool. Results FSR of mixed muscle protein was higher during the administration of citrulline than during NEAA (NEAA: 0.049 ± 0.005; citrulline: 0.060 ± 0.006; p=0.03), while muscle mitochondrial protein FSR and whole-body protein turnover were not different between the studies. Citrulline administration increased arginine and ornithine plasma concentrations without any effect on glucose, insulin, C-peptide, and IGF-1 levels. Citrulline administration did not promote mitochondria protein synthesis, transcripts, or citrate synthesis. Conclusions Citrulline ingestion enhances mixed muscle protein synthesis in healthy participants on 3-day low-protein intake. This anabolic action of citrulline appears to be independent of insulin action and may offer potential clinical application in conditions involving low amino acid intake.
    Clinical Nutrition 05/2014; · 3.94 Impact Factor
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    ABSTRACT: The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made (a) for healthy older people, the diet should provide at least 1.0-1.2 g protein/kg body weight/day, (b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2-1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.
    Clinical nutrition (Edinburgh, Scotland) 04/2014; · 3.27 Impact Factor
  • Diabetes 04/2014; 63(4):1169-70. · 7.90 Impact Factor
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    ABSTRACT: The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made: (1) for healthy older people, the diet should provide at least 1.0 to 1.2 g protein/kg body weight/day (2) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2 to 1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (3) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.
    Clinical Nutrition. 01/2014;
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    ABSTRACT: Insulin deprivation in type 1 diabetes (T1D) individuals increases lipolysis and plasma free fatty acids (FFA) concentration, which can stimulate synthesis of intramyocellular bioactive lipids, such as ceramides (Cer) and long chain fatty acid-CoAs (LCFa-CoAs). Ceramide was shown to decrease muscle insulin sensitivity and at mitochondrial level stimulates reactive oxygen species production. Here we show that insulin deprivation in streptozotocin diabetic C57BL/6 mice increases quadriceps muscle Cer content, which was correlated with concomitant decrease in the body fat and increased plasma FFA, glycosylated hemoglobin level (%A1C) and muscular LCFa-CoA content. The alternations were accompanied by increase in proteins expression in LCFa-CoA and Cer synthesis (FATP1/ACSVL5, CerS1, CerS5), decrease in the expression of genes implicated in muscle insulin sensitivity (GLUT4, GYS1) and inhibition of insulin signaling cascade by AKTα and GYS3β phosphorylation under acute insulin stimulation. Both the content and composition of sarcoplasmic fraction sphingolipids were most affected by insulin deprivation, whereas mitochondrial fraction sphingolipids remained stable. The observed effects of insulin deprivation were reversed except for content and composition of LCFa-CoA, CerS protein expression, GYS1 gene expression and phosphorylation status of AKT and GYS3β when exogenous insulin was provided by subcutaneous insulin implants. Principal component analysis and Pearson's correlation analysis revealed close relationships between the features of the diabetic phenotype, the content of LCFa-CoA's and Cer's containing C18-fatty acids in sarcoplasm, but not in mitochondria. Insulin replacement did not completely rescue the phenotype, especially regarding the content of LCFa-CoA, and proteins implicated in Cer synthesis and muscle insulin sensitivity.
    AJP Endocrinology and Metabolism 12/2013; 306(5). · 4.51 Impact Factor
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    ABSTRACT: Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.-Walrand, S., Short, K. R., Heemstra, L. A., Novak, C. M., Levine, J. A., Coenen-Schimke, J. M., Nair, K. S. Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.
    The FASEB Journal 12/2013; · 5.48 Impact Factor
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    ABSTRACT: Context:It has been suggested that mitochondrial dysfunctional in adipocytes contribute to obesity-related metabolic complications. However, obesity results in adipocyte hypertrophy, large and small adipocytes from the same depot have different characteristics, raising the possibility that obesity-related mitochondrial defects are an inherent function of large adipocytes.Objective:to examine whether obesity, independent of fat cell size and fat depot, is associated with mitochondria dysfunction.Design:cross-sectional comparison.Setting:Academic medical center.Patients or Other Participants:omental (OM) and/or abdominal subcutaneous (SQ) adipose samples were collected from 20, age-matched obese and non-obese non-diabetic men and women undergoing either elective abdominal surgery or research needle biopsy.Intervention:None.Main Outcome Measures:mitochondrial DNA abundance, oxygen consumption rates (OCR) and citrate synthase (CS) activity from populations of large and small adipocytes (separated with differential floatation).Results:For both omental and subcutaneous adipocytes, at the cell and organelle level, OCR and CS activity were significantly reduced in cells from obese compared with non-obese volunteers, even when matched for cell size by comparing large adipocytes from non-obese and small adipocytes from obese. Adipocyte mitochondrial content was not significantly different between obese and non-obese volunteers. Mitochondrial function and content parameters were not different between small and large cells, omental and subcutaneous adipocytes from the same person.Conclusion:Adipocyte mitochondrial oxidative capacity is reduced in obese compared to non-obese adults and this difference is not due to cell size differences. Adipocyte mitochondrial dysfunction in obesity is therefore related to overall adiposity rather than adipocyte hypertrophy.
    The Journal of Clinical Endocrinology and Metabolism 11/2013; · 6.31 Impact Factor
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    ABSTRACT: Upper-body, i.e. visceral, obesity is associated with insulin resistance and impaired protein synthesis. It is unclear whether postprandial stimulation of protein synthesis is affected by body fat distribution. We investigated the postprandial protein anabolic response in a cohort of obese women. Participants were studied after an overnight fast and after a mixed meal, grouped as upper-body obese (UBO, waist-to-hip ratio, WHR, >0.85, n = 6) vs. lower-body obese (LBO, WHR <0.80, n = 7). Lipid and carbohydrate metabolism were assessed by measurements of plasma free fatty acids (FFA), insulin and glucose plasma concentrations, and calculation of the Quicki index from fasting glucose and insulin values. Different labels of stable isotopes of phenylalanine were administered intravenously and orally, and leg and whole-body protein breakdown and synthesis were calculated from phenylalanine/tyrosine isotopic enrichments in femoral arterial and venous blood, using equations for steady-state kinetics. Data are denoted as mean ± SD. Age (38 vs. 40, p = 0.549) and body-mass index (33.7 ± 1.9 vs. 35.0 ± 1.8, p = 0.241) were similar in both groups. UBO subjects had more visceral fat (p = 0.002) and higher fat-free body mass (FFM) (p = 0.015). Plasma insulin concentrations were greater in UBO than LBO women (p = 0.013), and UBO were less insulin sensitive (Quicki = 0.32 ± 0.01 vs. 0.36 ± 0.02, p = 0.005). Protein kinetics across the leg were not different between groups. Fasting whole body protein balance was similarly negative in both groups (UBO -6.5 ± 2.4 vs. LBO -7.6 ± 0.9 μmol/kgFFM/h, p = 1.0). Postprandially, whole body protein balance became less positive in UBO than in LBO (14.8 ± 3.7 vs. 20.2 ± 3.7 μmol/kgFFM/h, p = 0.017). Whole-body protein balance following a meal is less positive in upper-body obese, insulin-resistant, women than in lower-body obese women.
    Clinical nutrition (Edinburgh, Scotland) 11/2013; · 3.27 Impact Factor
  • Adam R Konopka, K Sreekumaran Nair
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    ABSTRACT: With increasing age there is a temporal relationship between the decline of mitochondrial and skeletal muscle volume, quality and function (i.e., health). Reduced mitochondrial mRNA expression, protein abundance, and protein synthesis rates appear to promote the decline of mitochondrial protein quality and function. Decreased mitochondrial function is suspected to impede energy demanding processes such as skeletal muscle protein turnover, which is critical for maintaining protein quality and thus skeletal muscle health with advancing age. The focus of this review was to discuss promising human physiological systems underpinning the decline of mitochondrial and skeletal muscle health with advancing age while highlighting therapeutic strategies such as aerobic exercise and caloric restriction for combating age-related functional impairments.
    Molecular and Cellular Endocrinology 05/2013; · 4.24 Impact Factor
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    ABSTRACT: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) enhance insulin sensitivity and glucose homeostasis in rodent models of insulin resistance. These beneficial effects have been linked with anti-inflammatory properties, but emerging data suggests that the mechanisms may also converge on mitochondria. We evaluated the influence of dietary n-3 PUFAs on mitochondrial physiology and muscle lipid metabolites in the context of high-fat diet (HFD) in mice. Mice were fed control diets (10% fat), HFD (60% fat) or HFD with fish oil (HFD+FO, 3.4% kcals from n-3 PUFAs) for 10 weeks. Body mass and fat mass increased similarly in HFD and HFD+FO, but n-3 PUFAs attenuated the glucose intolerance that developed with HFD and increased expression of genes that regulate glucose metabolism in skeletal muscle. Despite similar muscle triglyceride levels in HFD and HFD+FO, long chain acyl coenzyme-As and ceramides were lower in the presence of fish oil. Mitochondrial abundance and oxidative capacity were similarly increased in HFD and HFD+FO compared to controls. Hydrogen peroxide production was similarly elevated in HFD and HFD+FO in isolated mitochondria, but not in permeabilized muscle fibers, likely due to increased activity and expression of catalase. These results support a hypothesis that n-3 PUFAs protect glucose tolerance, in part, by preventing the accumulation of bioactive lipid mediators that interfere with insulin action. Furthermore, the respiratory function of skeletal muscle mitochondria does not appear to be a major factor in sphingolipid accumulation, glucose intolerance, or the protective effects of n-3 PUFAs.
    AJP Endocrinology and Metabolism 04/2013; · 4.51 Impact Factor
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    ABSTRACT: Precise measurement of low enrichment of stable isotope labeled amino-acid tracers in tissue samples is a prerequisite in measuring tissue protein synthesis rates. The challenge of this analysis is augmented when small sample size is a critical factor. Muscle samples from human participants following an 8 h intravenous infusion of L-[ring-(13) C(6) ]phenylalanine and a bolus dose of L-[ring-(13) C(6) ]phenylalanine in a mouse were utilized. Liquid chromatography tandem mass spectrometry (LC/MS/MS), gas chromatography (GC) MS/MS and GC/MS were compared to the GC-combustion-isotope ratio MS (GC/C/IRMS), to measure mixed muscle protein enrichment of [ring-(13) C(6) ]phenylalanine enrichment. The sample isotope enrichment ranged from 0.0091 to 0.1312 molar percent excess. As compared with GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS showed coefficients of determination of R(2) = 0.9962 and R(2) = 0.9942, and 0.9217 respectively. However, the precision of measurements (coefficients of variation) for intra-assay are 13.0%, 1.7%, 6.3% and 13.5% and for inter-assay are 9.2%, 3.2%, 10.2% and 25% for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. The muscle sample sizes required to obtain these results were 8 µg, 0.8 µg, 3 µg and 3 µg for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. We conclude that LC/MS/MS is optimally suited for precise measurements of L-[ring-(13) C(6) ]phenylalanine tracer enrichment in low abundance and in small quantity samples. Copyright © 2013 John Wiley & Sons, Ltd.
    Biological Mass Spectrometry 02/2013; 48(2):269-75. · 2.71 Impact Factor
  • Matthew L Johnson, Matthew M Robinson, K Sreekumaran Nair
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    ABSTRACT: Decline in human muscle mass and strength (sarcopenia) is a hallmark of the aging process. A growing body of research in the areas of bioenergetics and protein turnover has placed the mitochondria at the center of this process. It is now clear that, unless an active lifestyle is rigorously followed, skeletal muscle mitochondrial decline occurs as humans age. Increasing research on mitochondrial biology has elucidated the regulatory pathways involved in mitochondrial biogenesis, many of which are potential therapeutic targets, and highlight the beneficial effects of vigorous physical activity on skeletal muscle health for an aging population.
    Trends in Endocrinology and Metabolism 01/2013; · 8.87 Impact Factor

Publication Stats

9k Citations
1,499.45 Total Impact Points


  • 1995–2014
    • Mayo Clinic - Rochester
      • • Department of Cardiovascular Diseases
      • • Department of Endocrinology, Diabetes, Metabolism and Nutrition
      Rochester, Minnesota, United States
  • 1997–2012
    • Mayo Foundation for Medical Education and Research
      • • Mayo School of Graduate Medical Education
      • • Department of Internal Medicine
      • • Division of Endocrinology, Diabetes, Metabolism, and Nutrition
      • • Division of Gastroenterology and Hepatology
      • • Department of Medicine
      Scottsdale, AZ, United States
  • 2008
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
    • Duke University Medical Center
      • Division of Endocrinology, Metabolism, and Nutrition
      Durham, North Carolina, United States
  • 2003–2008
    • Aarhus University Hospital
      • Department of Endocrinology and Internal Medicine
      Aarhus, Central Jutland, Denmark
    • University of Padova
      • Department of Information Engineering
      Padova, Veneto, Italy
  • 2006
    • Institut für Diabetes Gerhardt Katsch
      Karlsburg, Mecklenburg-Vorpommern, Germany
  • 1999
    • Karolinska Institutet
      Solna, Stockholm, Sweden
  • 1990–1999
    • University of Vermont
      • Department of Medicine
      Burlington, Vermont, United States
    • Monroe Community College
      Rochester, New York, United States
  • 1998
    • Karolinska University Hospital
      • Department of Surgery
      Stockholm, Stockholm, Sweden
  • 1996
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
    • University of Illinois at Chicago
      • Department of Medicine (Chicago)
      Chicago, IL, United States
  • 1987–1992
    • University of Rochester
      • Division of Hospital Medicine
      Rochester, New York, United States
  • 1983–1989
    • Florida Clinical Research Center
      Florida, United States