K Sreekumaran Nair

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (221)1194.14 Total impact

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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.
    09/2014;
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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.
    The Journal of clinical endocrinology and metabolism. 09/2014;
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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: 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. 01/2014;
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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 01/2014; 9(7):e102031. · 3.53 Impact Factor
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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; · 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; · 5.70 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; · 6.50 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; · 4.04 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. · 3.41 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; · 8.90 Impact Factor
  • Rozalina G McCoy, K Sreekumaran Nair
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    ABSTRACT: The past century had witnessed vast advances in biomedical research, particularly in the fields of genomics and proteomics, yet the translation of these discoveries into clinical practice has been hindered by gaps in mechanistic understanding of variability governing disease susceptibility and pathogenesis. Among the greatest challenges are the dynamic nature of the proteome and the imperfect methodologies currently available to study it. Here, we review key recently developed proteomic techniques that have allowed for dynamic characterization of protein quality, as well as quantity, and discuss their potential applications in understanding aging and metabolic disorders including diabetes. These methodologies revealed that senescence is characterized, in part, by decreased rates of de novo protein synthesis and potentially also degradation, in addition to concomitantly increased levels of oxidative stress, ultimately resulting in excessive accumulation of damaged and dysfunctional proteins. Insulin may be a key mediator in these pathologies, as hyperinsulinemia has been shown to hinder protein degradation while transient insulin deficiency may accelerate oxidative damage. We also discuss two interventions that have been proposed to delay, and possibly reverse, senescence by augmenting protein degradation: chronic caloric restriction and aerobic exercise.
    Clinical nutrition (Edinburgh, Scotland) 01/2013; · 3.27 Impact Factor
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    ABSTRACT: The response to mechanical stimuli, i.e., tensegrity, plays an important role in regulating cell physiological and pathophysiological function and the mechanical silencing observed in intensive care unit (ICU) patients leads to a severe and specific muscle wasting condition. This study aims at unravelling the underlying mechanisms and the effects of passive mechanical loading on skeletal muscle mass and function at the gene, protein and cellular levels. A unique experimental rat ICU model has been used allowing long-term (weeks) time-resolved analyses of the effects of standardized unilateral passive mechanical loading on skeletal muscle size and function and underlying mechanisms. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. the unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle mass and function is likely a consequence of a reduced oxidative stress revealed by lower levels of carbonylated proteins, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle size and function associated with the mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.
    The Journal of Physiology 12/2012; · 4.38 Impact Factor
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    ABSTRACT: PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
    Cell 12/2012; 151(6):1319-31. · 31.96 Impact Factor
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    ABSTRACT: Caloric restriction (CR) mitigates many detrimental effects of aging and prolongs life span. CR has been suggested to increase mitochondrial biogenesis, thereby attenuating age-related declines in mitochondrial function, a concept that is challenged by recent studies. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial oxidative capacity and efficiency, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis, which is further supported by lower mitochondrial protein synthesis with CR. We find that CR decreases oxidant emission, increases antioxidant scavenging, and minimizes oxidative damage to DNA and protein. These results demonstrate that CR preserves mitochondrial function by protecting the integrity and function of existing cellular components rather than by increasing mitochondrial biogenesis.
    Cell metabolism 12/2012; 16(6):777-88. · 17.35 Impact Factor
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Publication Stats

6k Citations
1,194.14 Total Impact Points

Institutions

  • 1995–2014
    • Mayo Clinic - Rochester
      • • Department of Hospital Internal Medicine
      • • Department of Endocrinology, Diabetes, Metabolism and Nutrition
      Rochester, Minnesota, United States
  • 2003–2012
    • University of Padova
      • Department of Information Engineering
      Padova, Veneto, Italy
  • 1997–2010
    • Mayo Foundation for Medical Education and Research
      • • Department of Internal Medicine
      • • Division of Endocrinology, Diabetes, Metabolism, and Nutrition
      • • Division of Gastroenterology and Hepatology
      • • Department of Medicine
      Rochester, Michigan, 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
  • 2006
    • Institut für Diabetes Gerhardt Katsch
      Karlsburg, Mecklenburg-Vorpommern, Germany
  • 1999
    • Karolinska Institutet
      Solna, Stockholm, Sweden
  • 1992–1999
    • University of Vermont
      • Department of Medicine
      Burlington, Vermont, United States
  • 1998
    • Karolinska University Hospital
      • Department of Surgery
      Stockholm, Stockholm, Sweden
  • 1996
    • University of Illinois at Chicago
      • Department of Medicine (Chicago)
      Chicago, IL, United States