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Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?

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Abstract

An age-dependent decline in skeletal muscle mass, strength, and endurance during the aging process is a physiological development, but several factors may exacerbate this process, leading to the threatening state of sarcopenia, frailty, and eventually higher mortality rates. Obesity appears to be such a promoting factor and has been linked in several studies to sarcopenia. The reason for this causal association remains poorly understood. Notwithstanding the fact that a higher body mass might simply lead to diminished physical activity and therefore contribute to a decline in skeletal muscle, several molecular mechanisms have been hypothesized. There could be an obesity derived intracellular lipotoxicity (i.e., elevated intramuscular levels of lipids and their derivatives), which induces apoptosis by means of an elevated oxidative stress. Paracrine mechanisms and inflammatory cytokines, such as CRP and IL-6 could be confounders of the actual underlying pathological mechanism. Due to a cross-talk of the hypothalamo-pituitary axis with nutritional status, obese subjects are more in a catabolic state of metabolism, with a higher susceptibility to muscle wasting under energy restriction. Obesity induces insulin resistance in the skeletal muscle, which consequently leads to perturbed metabolism, and misrouted signaling in the muscle cells. In obesity, muscle progenitor cells could differentiate to an adipocyte-like phenotype as a result of paracrine signals from (adipo)cytokines leading to a reduced muscular renewal capacity. The present review outlines current knowledge concerning possible pathways, which might be involved in the molecular pathogenesis of sarcopenic obesity.

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References

  • Adams JM, Pratipanawatr T, Berria R, Wand E, DeFronzo RA, Sullards MC, Mandarino LJ (2004) Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53:25–31

    CAS  PubMed  Google Scholar 

  • Allan CA, Strauss BJG, McLachlan RI (2007) Body composition, metabolic syndrome and testosterone in ageing men. Int J Impot Res 19:448–457

    CAS  PubMed  Google Scholar 

  • Allen DL, Hittel DS, Mcpherron AC (2011) Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med Sci Sports Exerc 43:1828–1835

    CAS  PubMed Central  PubMed  Google Scholar 

  • Anderson R, Prolla T (2009) PGC 1 alpha in aging and anti-aging interventions. Biochim Biophys Acta 1790:1059–1066

    CAS  PubMed Central  PubMed  Google Scholar 

  • Argiles JM, Orpi M, Busquets S, Lopez-Sorian F (2012) Myostatin: more than just a regulator of muscle mass. Drug Discov Today 17:702–709

    CAS  PubMed  Google Scholar 

  • Ballak DB, Van Essen P, Van Diepen JA, Jansen H, Hijams A, Matsuguchi T, Sparrer H, Tack CJ, Netea MG, Joosten LAB, Stienstra R (2014) MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without systemic effects in humans and mice. PLOS ONE 9

  • Batsis JA, Barre LK, Mackenzie TA, Pratt SI, Lopez-Jimenez F, Bartels SJ (2013) Variation in the prevalence of sarcopenia and sarcopenic obesity in older adults associated with different research definitions: dual-energy x-ray absorptiometry data from the National Health and Nutrition Examination Survey 1999–2004. J Am Geriatr Soc 61:974–980

    PubMed  Google Scholar 

  • Batsis JA, Mackenzie TA, Barre LK, Lopez-Jimenez F, Bartels SJ (2014) Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III. Eur J Clin Nutr 68:1001–1007

    CAS  PubMed  Google Scholar 

  • Baumgartner RN (2000) Body composition in healthy aging. Ann N Y Acad Sci 904:437–448

    CAS  PubMed  Google Scholar 

  • Baumgartner RN, Wayne SJ, Waters DL, Janssen I, Gallagher D, Morley JE (2004) Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res 12:1995–2004

    PubMed  Google Scholar 

  • Boldrin L, Muntoni F, Morgan JE (2010) Are human and mouse satellite cells really the same? J Histochem Cytochem 58:941–955

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bollheimer LC, Buettner R, Pongratz G, Brunner-Ploss R, Hechtl C, Banas M et al (2012) Sarcopenia in the aging high-fat fed rat: a pilot study for modeling sarcopenic obesity in rodents. Biogerontology 13:609–620

    CAS  PubMed  Google Scholar 

  • Bouchard DR, Dionne IJ, Brochu M (2009) Sarcopenic/obesity and physical capacity in older men and women: data from the nutrition as a determinant of successful aging (NuAge)—the Quebec Longitudinal Study. Obesity 17:2082–2088

    PubMed  Google Scholar 

  • Bouchonville MF, Villareal DT (2013) Sarcopenic obesity: how do we treat is? Endocrinology 20:412–419

    Google Scholar 

  • Boudou P, Sobngwi F, Mauvais-Jarvis P, Vexiau P, Gautier JF (2003) Absence of exercise-induced variations in adiponectin levels despite decreased abdominal adiposity and improved insulin sensitivity in type 2 diabetic men. Eur J Endocrin 149:421–424

    CAS  Google Scholar 

  • Boutcher SH (2011) High-intensity intermittent exercise and fat loss. J Obes. doi:10.1155/2011/868305

    PubMed Central  PubMed  Google Scholar 

  • Cai D, Frantz JD, Tawa NE Jr et al (2004) IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell 119:285–298. doi:10.1016/j.cell.2004.09.027

    CAS  PubMed  Google Scholar 

  • Camerino C (2009) Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity 17:980–984

    CAS  PubMed  Google Scholar 

  • Carbó N, Busquets S, van Royen M, Alvarez B, Lopez-Soriano FJ, Argiles JM (2002) TNF-alpha is involved in activating DNA fragmentation in skeletal muscle. Br J Cancer 86:1012–1016. doi:10.1038/sj.bjc.6600167

    PubMed Central  PubMed  Google Scholar 

  • Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L et al (2005) Sarcopenia, obesity, and inflammation—results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr 8(82):428–434

    Google Scholar 

  • Chen MB, McAinch AJ, Macaulay SL, Castelli LA, O’brien PE, Dixon JB, Cameron-Smith D, Kemp BE, Steinberg GR (2005) Impaired activation of AMP-kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics. J Clin Endocrinol Metab 90:3665–3672

    CAS  PubMed  Google Scholar 

  • Chia DJ, Ono M, Woelfle J, Schlesinger-Massart M, Jiang H, Rotwein P (2006) Characterization of distinct Stat5b binding sites that mediate growth hormone-stimulated IGF-I gene transcription. J Biol Chem 281:3190–3197

    CAS  PubMed  Google Scholar 

  • Choi CS, Befroy DE, Codella R, Kim S, Reznick RM, Hwang YJ, Liu ZX, Lee HY, Distefano A, Samuel VT, Zhang D, Cline GW, Handschin C, Lin J, Petersen KF, Spiegelman BM, Shulman GI (2008) Paradoxical effects of increased expression of PGC-1 alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc Nat Acad Sci 105:19926–19931

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ciciliot S, Schiaffino S (2010) Regeneration of mammalian skeletal muscle. Basic mechanisms and clinical implications. Curr Pharm Des 16:906–914

    CAS  PubMed  Google Scholar 

  • Consitt LA, Bell JA, Houmard JA (2009) Intramuscular lipid metabolism, insulin action and obesity. IUBMB Life 61:47–55

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cooper R, Kuh D, Cooper C, Gale CR, Lawlor DA, Matthews F, Hardy R, The FALCon and HALCyon Study Teams (2011) Objective measures of physical capability and subsequent health: a systematic review. Age Ageing 40:4–23

    Google Scholar 

  • Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F et al (2010) Sarcopenia: European consensus on definition and diagnosis. Age Ageing 39:412–423

    PubMed Central  PubMed  Google Scholar 

  • Deblon N, Veyrat-Durebex C, Bourgoin L, Caillon AK, Bussier A-L, Petrosino S, Piscitelli F, Legros J-J, Geenen V, Foti M, Wahli W, Di Marzo V, Rohner-Jeanrenaud F (2011) Mechanisms of the ant-obesity effects of oxytocin in diet-induced obese rats. PLoS ONE 6:e25565

    CAS  PubMed Central  PubMed  Google Scholar 

  • Derbré F, Gomez-Cabrera MC, Nascimento AL, Sanchis-Gomar F, Martinez-Bello VE, Tresguerres JAF et al (2012) Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training. AGE 34:669–679

    PubMed Central  PubMed  Google Scholar 

  • Doak CM, Wijnhoven TMA, Schokker DF, Visscher TLS, Seidell JC (2012) Age standardization in mapping adult overweight and obesity trends in the WHO European Region. Obes Rev 13:174–191

    CAS  PubMed  Google Scholar 

  • Donges CE, Duffield R, Drinkwater EJ (2010) Effects of resistance or aerobic exercise training on interleukin-6, C-reactive protein, and body composition. Med Sci Sports Exerc 42:304–313

    CAS  PubMed  Google Scholar 

  • Donnelly JE, Blair S, Jakicic J, Manore M, Rankin J, Smith B (2009) American college of sports medicine position stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc 41:459–471

    PubMed  Google Scholar 

  • Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, Kung S, Jiang KP, Conboy IM (2014) Oxytocin is an age-specific circulation hormone that is necessary for muscle maintenance and regeneration. Nat Commun 5:4082/doi: 10.1038/ncomms5082

  • Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, et al (2008) Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 299:3952

  • Espinoza DO, Boros LG, Crunkhorn S, Gami H, Patti ME (2010) Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator -1alpha and -1beta in cultured myotubes. FASEB 24:1003–1014

    CAS  Google Scholar 

  • Fellner C, Schick F, Kob R, Hecht C, Vorbuchner M, Büttner R, Hamer OW, Sieber CC, Stroszczynski C, Bollheimer LC (2014) Diet-induced and age-related changes in the quadriceps muscle: MRI and MRS in a rat model of sarcopenia. Gerontology. doi:10.1159/000360289

    PubMed  Google Scholar 

  • Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ (1990) High-intensity strength training in nonagenarians. Effects on skeletal muscle. JAMA 263:3029–3034

    CAS  PubMed  Google Scholar 

  • Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE et al (2011) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology and consequences. J Am Med Dir Assoc 12:249–256

    PubMed  Google Scholar 

  • Florez H, Troen BR (2008) Fat and inflammaging: a dual path to unfitness in elderly people? J Am Geriatr Soc 56:558–560

    PubMed  Google Scholar 

  • Florini JR, Ewton DZ, Coolican SA (1996) Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev 17:481–517

    CAS  PubMed  Google Scholar 

  • Frimel TN, Dinacore DR, Villarreal T (2008) Exercise attenuates the weight-loss-induced reduction in muscle mass in frail obese older adults. Med Sci Sports Exerc 40:1213–1219

    PubMed Central  PubMed  Google Scholar 

  • Frontera WR, Meredith CN, O’Reilly KP, Knuttgen HG, Evans WJ (1988) Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol 64:1038–1044

    CAS  PubMed  Google Scholar 

  • Fujita S, Rasmussen BB, Cadenas JG, Drummond MJ, Glynn EL, Sattler FR, Volpi E (2007) Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes 56:1615–1622

    CAS  PubMed Central  PubMed  Google Scholar 

  • Garris D (2005) Cytochemical analysis of pancreatic islet lipoapoptosis: hyperlipidemia-induced cytoinvolution following expression of the diabete (db/db) mutation. Pathobiology 72:124–132

    CAS  PubMed  Google Scholar 

  • Goodpaster BH, He J, Watkins S, Kelley DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86:5755–5761

    CAS  PubMed  Google Scholar 

  • Griffin ME, Marcucci MJ, Clone GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI (1999) Free fatty acid-induced insulin resistance is associated with activation of protein kinase c theta and alteration in the insulin signaling cascade. Diabetes 48:1270–1274

    CAS  PubMed  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Geront 11:298–300

    CAS  PubMed  Google Scholar 

  • Herbst A, Pak JW, McKenzie D, Bua E, Bassiouni M, Aiken JM (2007) Accumulation of mitochondrial DNA mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss. J Geront A Biol Sci Med Sci 62:235–245

    Google Scholar 

  • Hittel DS, Berggren JR, Shearer J, Boyle K, Houmard JA (2009) Increased secretion and expression of myostatin in skeletal muscle from extremely obese women. Diabetes 58:30–38

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iossa S, Lionetti L, Mollica MP, Crescenzo R, Barletta A, Liverini G (2001) Fat balance and serum leptin concentrations in normal, hypothyroid, and hyperthyroid rats. Int J Obes Relat Metab Disord J Int Assoc Study Obes 25:417–425

    CAS  Google Scholar 

  • Jacob S, Machann J, Rett K, Brechtel K, Volk A, Renn W, Maerker E, Matthaei S, Schick F, Claussen CD, Häring HU (1999) Association of increased intramyocellular lipid contend with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes 42:1113–1119

    Google Scholar 

  • Kadi F, Ponsol E (2010) The biology of satellite cells and telomeres in human skeletal muscle: effects of aging and physical activity. Scan J Med Sci Sports 20:39–48

    CAS  Google Scholar 

  • Kennedy RL, Chokkalingham K, Srinivasan R (2004) Obesity in the elderly: who should we be treating, and why, and how? Curr Opin Clin Nutr Metab Care 7:3–9

    PubMed  Google Scholar 

  • Kohut ML, McCann DA, Russell DW, Konopka DN, Cunnick JE, Franke WD et al (2006) Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of β-blockers, BMI, and psychosocial factors in older adults. Brain Behav Immun 20:201–209

    CAS  PubMed  Google Scholar 

  • Kok P, Roelfsema F, Langendonk JG, Frölich M, Burggraaf J, Meinders AE et al (2005) High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction. J Clin Endocrinol Metab 90:4659–4663

    CAS  PubMed  Google Scholar 

  • Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI (1999) Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 42:113–116

    CAS  PubMed  Google Scholar 

  • Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE (2009) Diabetes and apoptosis: lipotoxicity. Apoptosis 14:1484–1495

    CAS  PubMed  Google Scholar 

  • La Cava A, Matarese G (2004) The weight of leptin in immunity. Nature Rev Immunol 4:371–379

    Google Scholar 

  • Lambert CP, Wright NR, Finck BN, Villareal DT (2008) Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons. J Appl Physiol 105:473–478

    CAS  PubMed Central  PubMed  Google Scholar 

  • Landi F, Cruz-Jentoft AJ, Liperoti R, Russo A, Giovannini S, Tosato M, Capoluongo E, Bernabei R, Graziano O (2013) Sarcopenia and mortality risk in frail older persons aged 80 years and older: result from ilSIRENTE study. Age Ageing 42:203–209

    PubMed  Google Scholar 

  • Lanning NJ, Carter-Su C (2006) Recent advances in growth hormone signaling. Rev Endocr Metab Disord 7:225–235

    CAS  PubMed  Google Scholar 

  • Lanza IR, Nair KS (2009) Muscle mitochondrial changes with aging and exercise (2009) Muscle mitochondrial changes with aging and exercise. Am J Clin Nutr 89:467S–471S

    CAS  PubMed Central  PubMed  Google Scholar 

  • Latham N, Anderson C, Bennet D, Stretton C (2003) Progressive resistance strength training for physical disability in older people. Cochrane Database Syst Rev 2:CD002759

  • LeBrasseur NK (2012) Building muscle, browning fat and preventing obesity by inhibiting myostatin. Diabetologia 55:13–17

    CAS  PubMed  Google Scholar 

  • Lee S-J (2004) Regulation of muscle mass by myostatin. Ann Rev Cell Dev Biol 20:61–86

    CAS  Google Scholar 

  • Levine ME, Crimmins EM (2012) The impact of insulin resistance and inflammation on the association between sarcopenic obesity and physical functioning. Obesity 20:2101–2106

    CAS  PubMed Central  PubMed  Google Scholar 

  • Magnuson B, Ekim B, Fingar DC (2012) Regulation and function of ribosomal protein S6 kinase (S6 K) within mTOR signaling networks. Biochem J 441:1–21

    CAS  PubMed  Google Scholar 

  • Marzetti E, Carter CS, Wohlgemuth SE, Lees HA, Giovannini S, Anderson B et al (2009) Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mech Ageing Dev 130:272–280

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marzetti E, Hwang JC, Less HA, Wohlgemuth SE, Dupont-Versteegden EE, Carter CS, Benabei R, Leeuwenburgh C (2010) Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta 1800:235–244

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mathus-Vliegen EMH, on behalf of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO) (2012) Prevalence, pathophysiology, health consequences and treatment of obesity in the elderly: a guideline. Obes Facts 5:460–483

    Google Scholar 

  • Muscaritoli M, Anker SD, Argiles J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Gearon KC, Laviano A, Maggio M, Rossi Fanelli F, Schneider SM, Schols A, Sieber CC (2010) Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by special interest groups (SIG) Cachexia-anorexia in chronic wasting diseases and nutrition in geriatrics. Clin Nutr 29:154–159

    CAS  PubMed  Google Scholar 

  • Nicklas BJ, Hsu F-C, Brinkley TJ, Church T, Goodpaster BH, Kritchevsky SB et al (2008) Exercise training and plasma C-reactive protein and interleukin-6 in the elderly. J Am Geriatr Soc 56:2045–2052

    PubMed Central  PubMed  Google Scholar 

  • Nilsson MI, Dobson JP, Greene NP, Wiggs MP, Shimkus KL, Wudeck EV et al (2013) Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. doi:10.1096/fj.12-224006

    PubMed Central  Google Scholar 

  • Pedersen BK, Febbraio MA (2008) Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 88:1379–1406

    CAS  PubMed  Google Scholar 

  • Pratesi A, Tarantini F, Di Bari M (2013) Skeletal muscle: an endocrine organ. Clin Cases Miner Bone Metab 10:11–14

    PubMed Central  PubMed  Google Scholar 

  • Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, Argilés JM (2002) Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders. Exp Cell Res 280:55–63

    CAS  PubMed  Google Scholar 

  • Reznick RM, Zhong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH, Shulman GI (2007) Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell 5:151–156

    CAS  Google Scholar 

  • Rolland Y, Lauwers-Cances V, Cristini C, van Kan GA, Janssen I, Morley JE et al (2009) Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l’OSteoporose) Study. Am J Clin Nutr 89:1895–1900

    CAS  PubMed  Google Scholar 

  • Roubenoff R (2003) Catabolism of aging: is it an inflammatory process? Curr Opin Clin Nutr Metab Care 6:295–299

    PubMed  Google Scholar 

  • Ryall JG, Schertzer JD, Lynch GS (2008) Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology 9:213–228

    CAS  PubMed  Google Scholar 

  • Sainsbury A, Zhang L (2012) Role of the hypothalamus in the neuroendocrine regulation of body weight and composition during energy deficit. Obes Rev 13:234–257

    CAS  PubMed  Google Scholar 

  • Sakuma K, and Yamaguchi A (2013) Sarcopenic obesity and endocrinal adaptation with age. Int J Endocrinol 204164. doi: 10.1155/2013/204164

  • Sakuma K, Watanabe K, Hotta N, Koike T, Ishida K, Katayama K, Akima H (2009) The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humans. Acta Physiol 197:151–159

    CAS  Google Scholar 

  • Sakuma K, Aoi W, Yamaguchi A (2014) Current understanding of sarcopenia: possible candidates modulating muscle mass. Pflugers Arch—Eur J Physiol 1–17

  • Schaap LA, Pluijm SMF, Deeg DJH, Visser M (2006) Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med 119:526.e9–526.e1

  • Schrager MA, Metter EJ, Simonsick E, Ble A, Bandinelli S, Lauretani F, Ferrucci L (2007) Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 102:919–925

    PubMed Central  PubMed  Google Scholar 

  • Sepe A, Tchkonia T, Thomou T, Zamboni M, Kirkland JL (2011) Aging and regional differences in fat cell progenitors—a mini-review. Gerontology 57:66–75

    PubMed  Google Scholar 

  • Shimabukuro M, Zhou Y-T, Levi M, Unger RH (1998) Fatty acid-induced β cell apoptosis: a link between obesity and diabetes. Proc Nat Acad Sci USA 95:2498–2502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sparangna G, Hickson-bick D (2000) A metabolic role for mitochondria in palmitate-induced cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol 279:H2124–H2132

    Google Scholar 

  • Stenholm S, Harris TB, Rantanen MS, Visser M, Kritchevsky SB, Ferrucci L (2008a) Sarcopenic obesity—definition, etiology and consequences. Curr Opin Clin Nutr Metab Care 11:693–700

    PubMed Central  PubMed  Google Scholar 

  • Stenholm S, Rantanen T, Heliövaara M, Koskinen S (2008b) The mediating role of c-reactive protein and handgrip strength between obesity and walking limitation. J Am Geriatr Soc 56:462–469

    PubMed  Google Scholar 

  • St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivator. Cell 20:397–408

    Google Scholar 

  • Summermatter S, Thurnheer R, Santos G, Mosca B, Baum O, Treves S et al (2012) Remodeling of calcium handling in skeletal muscle through PGC-1α: impact on force, fatigability, and fiber type. Am J Physiol—Cell Physiol 302:C88–C99

    CAS  PubMed  Google Scholar 

  • Summers SA (2006) Ceramide in insulin resistance and lipotoxicity. Progr Lipid Res 45:42–72

    CAS  Google Scholar 

  • Takayanagi Y, Kasahara Y, Onaka T, Takahashi N, Kaeada T, Nishimori K (2008) Oxytocin receptor-deficient mice developed late-onset obesity. NeuroReport 19:951–955

    CAS  PubMed  Google Scholar 

  • Tapp EG, Chisholm DJ, Freund J, Boutcher SH (2008) The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women. Int J Obes 32:684–691

    Google Scholar 

  • Thornell LE (2011) Sarcopenic obesity: satellite cells in the aging muscle. Curr Opin Clin Nutr Metab Care 14:22–27

    PubMed  Google Scholar 

  • Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783

    CAS  PubMed  Google Scholar 

  • Timmerman KL, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Jennins K, Rasmussen BB, Volpi E (2012) A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults. Am J Clin Nutr 95:1403–1412

    CAS  PubMed Central  PubMed  Google Scholar 

  • Turpin SM, Ryall JG, Southgate R, Darby I, Hevener AL, Febbraio MA et al (2009) Examination of lipotoxicity’ in skeletal muscle of high-fat fed and ob/ob mice. J Physiol 587:1593–1605

    CAS  PubMed Central  PubMed  Google Scholar 

  • Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferrando A (1995) Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 32:E820–E826

    Google Scholar 

  • Van Herpen NA, Schrauwen-Hinderling VB (2008) Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 94:231–241

    PubMed  Google Scholar 

  • Vilarrasa N, Vendrell J, Maravall J, Broch M, Estepa A, Begia A, Soler J, Simon I, Richart C, Gomez JM (2005) Distribution and determinants of adiponectin, resistin and ghrelin in a randomly selected healthy population. Clin Endocrinol 63:329–335

    CAS  Google Scholar 

  • Villareal DT, Smith GI, Sinacore DR, Shah K, Mittendorfer B (2011) Regular multi-component exercise increases physical fitness and muscle protein anabolism in frail, obese, older adults. Obesity 19:312–318

    CAS  PubMed Central  PubMed  Google Scholar 

  • Volkert D (2013) Malnutrition in older adults-urgent need for action: a plea for improving the nutritional situation of older adults. Gerontology 59:328–333

    PubMed  Google Scholar 

  • Volkert D, Sieber CC (2011) Protein requirements in the elderly. Int J Vitam Nutr Res 81:109–119

    CAS  PubMed  Google Scholar 

  • Walker DK, Dickinson JM, Timmerman KL, Drummond MJ, Reidy PT, Fry CA, Gundermann DM, Rasmussen BB (2011) Exercise, amino acids and aging in the control of human muscle protein synthesis. Med Sci Sports Exerc 43:2249–2258

    CAS  PubMed Central  PubMed  Google Scholar 

  • Waters DL, Baumgartner RN, Garry PJ, Vellas B (2010) Advantages of dietary, exercise-related, and therapeutic interventions to prevent and treat sarcopenia in adult patients: an update. Clin Interv Aging 5:259–270)

  • Watt MJ, Hebvener A, Lancaster GI, Febbraio MJ (2006) CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 12:541–548

    CAS  PubMed  Google Scholar 

  • Wei Y, Wand D, Topczewski F, Pagliassotti MJ (2006) Saturated fatty acids induce endoplasmatic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 291:E275–E281

    CAS  PubMed  Google Scholar 

  • Wende AR, Schaeffler PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancook CR, Lehmann JJ, Huss JM, McClain DA, Hollszy JO, Kelly DP (2007) A role for the transcriptional coactivator PGC-1 alpha in muscle refueling. J Biol Chem 282:36642–36651

    CAS  PubMed  Google Scholar 

  • Wenz T, Rossi SG, Rotundo RG, Spiegelman BM, Moraes CT (2009) Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging. Proc Nat Acad Sci USA 106:20405–20410

    CAS  PubMed Central  PubMed  Google Scholar 

  • White TA, LeBrasseur NK (2014) Myostatin and sarcopenia: opportunities and challenges—a mini-review. Gerontology 60:289–293

    CAS  PubMed  Google Scholar 

  • Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T (2007) Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients. A randomized study. Circulation 115:3086–3094

    PubMed  Google Scholar 

  • Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Ananuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty acid oxidation by activating AMP-activated protein kinase. Nat Med 11:1288–1295

    Google Scholar 

  • Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekaea S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769

    CAS  PubMed  Google Scholar 

  • Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF (2002) Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting. J Nutr Health Aging 6:343–348

    CAS  PubMed  Google Scholar 

  • Yeap BB, Paul Chubb SA, Lopez D, Ho KKY, Hankey GJ, Flicker L (2012) Associations of insulin-like growth factor-I and its binding proteins, and testosterone, with frailty in older men. Clin Endocrinol 78:752–759

    Google Scholar 

  • Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Franchesco V, Fantin F, Bissoli L, Bosello O (2005) Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes 29:1011–1029

    CAS  Google Scholar 

  • Zamboni M, Mazzali G, Fantin F, Rossi A, Di Franchesco V (2008) Sarcopenic obesity: a new category of obesity in the elderly. Nutr Metab Cardiovasc Dis 18:388–395

    CAS  PubMed  Google Scholar 

  • Zhang G, Bai H, Zhang H, Dean C, Wu Q, Li J, Guariglia S, Meng Q, Cai D (2011) Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron 69:523–535

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank the Bayerische Forschungsstiftung which supports the working group within the research association “Amyotrophia (Sarcopenia) and Osteoporosis—Consequence of limited regeneration in age (FORMOsA).

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No conflicts of interest.

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Authors and Affiliations

  1. Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Kobergerstraße 60, 90408, Nuremberg, Germany

    Robert Kob, L. Cornelius Bollheimer, Cornel C. Sieber & Barbara E. Fischer

  2. Department of General Internal Medicine and Geriatrics, St. John of God Hospital, Regensburg, Germany

    L. Cornelius Bollheimer & Cornel C. Sieber

  3. Laboratory Medicine and Transfusion Medicine, Institute of Clinical Chemistry, Paracelsus Medical University, Nuremberg, Germany

    Thomas Bertsch

  4. Institute of Radiology, University Hospital Regensburg, Regensburg, Germany

    Claudia Fellner

  5. Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany

    Marija Djukic

  6. Department of Neuropathology, University Medical School Göttingen, Göttingen, Germany

    Marija Djukic

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  1. Robert Kob
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  2. L. Cornelius Bollheimer
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  3. Thomas Bertsch
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  4. Claudia Fellner
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  5. Marija Djukic
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  6. Cornel C. Sieber
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  7. Barbara E. Fischer
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Corresponding author

Correspondence to Barbara E. Fischer.

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Kob, R., Bollheimer, L.C., Bertsch, T. et al. Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?. Biogerontology 16, 15–29 (2015). https://doi.org/10.1007/s10522-014-9539-7

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  • DOI: https://doi.org/10.1007/s10522-014-9539-7

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