K Sreekumaran Nair

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

Are you K Sreekumaran Nair?

Claim your profile

Publications (274)1675.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Decline in mitochondrial DNA (mtDNA) copy number, function, and accumulation of mutations and deletions have been proposed to contribute to age-related physical decline, based on cross sectional studies in genetically unrelated individuals. There is wide variability of mtDNA and functional measurements in many population studies and therefore we assessed mitochondrial function and physical function in 18 families of grandmothers, mothers, and daughters who share the same maternally inherited mtDNA sequence. A significant age-related decline in mtDNA copy number, mitochondrial protein expression, citrate synthase activity, cytochrome c oxidase content, and VO2 peak were observed. Also, a lower abundance of SIRT3, accompanied by an increase in acetylated skeletal muscle proteins, was observed in grandmothers. Muscle tissue-based full sequencing of mtDNA showed greater than 5% change in minor allele frequency over a lifetime in two locations, position 189 and 408 in the noncoding D-loop region but no changes were noted in blood cells mtDNA. The decline in oxidative capacity and muscle function with age in three generations of women who share the same mtDNA sequence are associated with a decline in muscle mtDNA copy number and reduced protein deacetylase activity of SIRT3. © The Author 2015. 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 08/2015; DOI:10.1093/gerona/glv086 · 4.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stable isotope-labeled amino acids have long been used to measure the fractional synthesis rate of proteins, although the mass spectrometry platforms used for such analyses have changed throughout the years. More recently, tandem mass spectrometers such as triple quadrupoles have been accepted as the standard platform for enrichment measurement due to their sensitivity and the enhanced specificity offered by multiple reaction monitoring (MRM) experiments. The limit in the utility of such platforms for enrichment analysis occurs when measuring very low levels of enrichment from small amounts of sample, particularly proteins isolated from two-dimensional gel electrophoresis (2D-GE), where interference from contaminant ions impacts the sensitivity of the measurement. We therefore applied a high-resolution orbitrap mass spectrometer to the analysis of [ring-(13)C6]-phenylalanine enrichment in individual muscle proteins isolated with 2D-GE. Comparison of samples analyzed on both platforms revealed that the high-resolution MS has significantly improved sensitivity relative to the triple quadrupole MS at very low-level enrichments due to its ability to resolve interferences in the m/z dimension. At higher enrichment levels, enrichment measurements from the orbitrap platform showed significant correlation (R (2) > 0.5) with those of the triple quadrupole platform. Together, these results indicate that high-resolution MS platforms such as the orbitrap are not only as capable of performing isotope enrichment measurements as the more commonly preferred triple quadrupole instruments, but offer unparalleled advantages in terms of mass accuracy and sensitivity in the presence of similar-mass contaminants.
    Analytical and Bioanalytical Chemistry 04/2015; 407(14). DOI:10.1007/s00216-015-8641-2 · 3.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To examine the association of gene variants of uncoupling proteins (UCP)-2 and −3 with obesity and gastrointestinal (GI) traits.Methods In 255 overweight or obese adults, the associations of gene variants in UCP-2 (−3474, rs659366) and UCP-3 (rs1626521, rs2075577, rs15763) with body weight (BW) and GI traits were studied. Gene variants were genotyped by TaqMan® assay. The associations of genotypes with BW and GI traits (gastric emptying, gastric volume, satiety by buffet meal, satiation by nutrient drink test and GI hormones) were assessed using ANOVA corrected for false detection rate (FDR).ResultsA novel UCP-3 gene variant, rs1626521, was identified; it was associated with BW (P = 0.039), waist circumference (P = 0.035), and significantly higher postprandial gastric volume (P = 0.003) and calories ingested at buffet meal (P = 0.006, both significant with FDR). In a subgroup of 11 participants, rs1626521 was also associated with reduced mitochondrial bioenergetics efficiency in skeletal muscle (P = 0.051). In an in vitro study in HEK293 cells, rs1626521 reduced UCP-3 protein expression (P = 0.049). Associations detected between other genotypes and GI traits were nonsignificant with FDR.ConclusionsA newly identified functional variant (rs1626521) in UCP-3 affects postprandial gastric functions and satiety and may contribute to weight gain and alter human mitochondrial function.
    Obesity 03/2015; 23(4). DOI:10.1002/oby.21039 · 4.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg twice per day, N=12 participants) or placebo (N=13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites. Copyright © 2015 Elsevier Inc. All rights reserved.
    Metabolism: clinical and experimental 01/2015; 64(6). DOI:10.1016/j.metabol.2015.01.008 · 3.61 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 64(6). DOI:10.2337/db14-1701 · 8.47 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Journal of Clinical Endocrinology &amp Metabolism 01/2015; 100(4):jc20143081. DOI:10.1210/jc.2014-3081 · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; DOI:10.1093/gerona/glu221 · 4.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    12/2014; 2(12). DOI:10.14814/phy2.12239
  • [Show abstract] [Hide abstract]
    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; DOI:10.4158/EP11314.STMNT · 2.59 Impact Factor
  • Alice Y. Chang · Tumpa Dutta · Surendra Dasari · K. Sreekumaran Nair
    Journal of Women's Health 10/2014; 23(10):854-854. · 1.90 Impact Factor
  • F González · K Sreekumaran Nair · E Basal · D M Bearson · J M Schimke · H E Blair
    [Show abstract] [Hide abstract]
    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; 47(06). DOI:10.1055/s-0034-1387791 · 2.04 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 99(12):jc20142736. DOI:10.1210/jc.2014-2736 · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim 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. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.
    PLoS ONE 07/2014; 9(7):e102031. DOI:10.1371/journal.pone.0102031 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 34(3). DOI:10.1016/j.clnu.2014.04.019 · 3.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; 33(6). DOI:10.1016/j.clnu.2014.04.007 · 3.94 Impact Factor
  • Source
    Diabetes 04/2014; 63(4):1169-70. DOI:10.2337/db14-0067 · 8.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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). DOI:10.1152/ajpendo.00610.2012 · 4.09 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 28(3). DOI:10.1096/fj.13-239806 · 5.48 Impact Factor
  • Nutrition Metabolism and Cardiovascular Diseases 12/2013; 23:S56. DOI:10.1016/j.numecd.2013.10.021 · 3.88 Impact Factor

Publication Stats

11k Citations
1,675.99 Total Impact Points

Institutions

  • 1994–2015
    • Mayo Clinic - Rochester
      • • Department of Endocrinology, Diabetes, Metabolism and Nutrition
      • • Department of Cardiovascular Diseases
      Рочестер, Minnesota, United States
  • 2014
    • University of Michigan
      • Department of Ophthalmology and Visual Sciences
      Ann Arbor, 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
    • Rochester College
      Rochester, New York, United States
  • 2004–2006
    • Mayo Foundation for Medical Education and Research
      • Division of Endocrinology, Diabetes, Metabolism, and Nutrition
      Scottsdale, AZ, United States
  • 2003
    • University of Padova
      • Department of Information Engineering
      Padova, Veneto, Italy
  • 1987–2002
    • University of Rochester
      • Division of Hospital Medicine
      Rochester, New York, United States
  • 1999
    • Aarhus University Hospital
      • Department of Endocrinology and Internal Medicine
      Aarhus, Central Jutland, Denmark
  • 1990–1999
    • University of Vermont
      • • Division of Endocrinology, Diabetes and Metabolism
      • • Department of Medicine
      Burlington, Vermont, United States
  • 1998
    • Abbott Laboratories
      • Abbott Laboratories
      North Chicago, Illinois, United States
    • University of Vermont Medical Center
      Burlington, Vermont, United States
  • 1996
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States