, Volume 16, Issue 2, pp 235–248 | Cite as

Ageing, adipose tissue, fatty acids and inflammation

  • Chathyan PararasaEmail author
  • Clifford J. Bailey
  • Helen R. Griffiths
Review Article


A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.


Ageing Adipose Ceramide Saturated fatty acids Inflammation Insulin resistance 



We would like to acknowledge the BBSRC Targeted Priority Studentship in Ageing scheme which funded CP.


  1. Aasen G, Fagertun H, Tonstad S, Halse J (2009) Leg fat mass as measured by dual X-ray absorptiometry (DXA) impacts insulin resistance differently in obese women versus men. Scand J Clin Lab Investig 69:181–189. doi: 10.1080/00365510802464641 Google Scholar
  2. Adams JM, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, Sullards MC, Mandarino LJ (2004) Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53:25–31PubMedGoogle Scholar
  3. Amati F et al (2011) Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance another paradox in endurance-trained athletes? Diabetes 60:2588–2597. doi: 10.2337/db10-1221 PubMedCentralPubMedGoogle Scholar
  4. Anderwald C et al (2002) Effects of insulin treatment in type 2 diabetic patients on intracellular lipid content in liver and skeletal muscle. Diabetes 51:3025–3032PubMedGoogle Scholar
  5. Assmann A, Mohlig M, Osterhoff M, Pfeiffer AFH, Spranger J (2008) Fatty acids differentially modify the expression of urokinase type plasminogen activator receptor in monocytes. Biochem Biophys Res Commun 376:196–199. doi: 10.1016/j.bbrc.2008.08.115 PubMedGoogle Scholar
  6. Bartlett DB et al (2012) The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection. Aging Cell 11:912–915. doi: 10.1111/j.1474-9726.2012.00849.x PubMedGoogle Scholar
  7. Bastie CC, Hajri T, Drover VA, Grimaldi PA, Abumrad NA (2004) CD36 in myocytes channels fatty acids to a lipase-accessible triglyceride pool that is related to cell lipid and insulin responsiveness. Diabetes 53:2209–2216PubMedGoogle Scholar
  8. Bays HE et al (2008) Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther 6:343–368. doi: 10.1586/14779072.6.3.343 PubMedGoogle Scholar
  9. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S (2005) Prevalence of and risk factors for nonalcoholic fatty liver disease: the dionysos nutrition and liver study. Hepatology 42:44–52PubMedGoogle Scholar
  10. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C (2006) The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population Bmc. Gastroenterology 6:33. doi: 10.1186/1471-230x-6-33 PubMedCentralPubMedGoogle Scholar
  11. Berneburg M (2010) Research in practice: more than skin deep -aging of subcutaneous fat tissue. J der Deutschen Dermatologischen Gesellschaft = J German Soc Dermatol: JDDG 8:776–778. doi: 10.1111/j.1610-0387.2010.07480.x Google Scholar
  12. Bethel M, Chitteti BR, Srour EF, Kacena MA (2013) The changing balance between osteoblastogenesis and adipogenesis in aging and its impact on hematopoiesis. Curr Osteoporos Rep 11:99–106. doi: 10.1007/s11914-013-0135-6 PubMedCentralPubMedGoogle Scholar
  13. Bjorntorp P (1990) Portal adipose-tissue as a generator of risk-factors for cardiovascular-disease and diabetes. Arteriosclerosis 10:493–496PubMedGoogle Scholar
  14. Bonen A et al (2004) Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36. Faseb J 18:1144–1146Google Scholar
  15. Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A, Heigenhauser GJF, Dyck DJ (2006) Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am J Physiol-Endocrinol Metab 291:E99–E107. doi: 10.1152/ajpendo.00587.2005 PubMedGoogle Scholar
  16. Cartwright MJ, Tchkonia T, Kirkland JL (2007) Aging in adipocytes: potential impact of inherent, depot-specific mechanisms. Exp Gerontol 42:463–471PubMedCentralPubMedGoogle Scholar
  17. Chavez JA, Summers SA (2003) Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2Cl2 myotubes. Arch Biochem Biophys 419:101–109. doi: 10.1016/ PubMedGoogle Scholar
  18. Chavez JA, Summers SA (2012) A ceramide-centric view of insulin resistance. Cell Metab 15:585–594. doi: 10.1016/j.cmet.2012.04.002 PubMedGoogle Scholar
  19. Cinti S et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355. doi: 10.1194/jlr.M500294-JLR200 PubMedGoogle Scholar
  20. Claycombe KJ, Wu DY, Nikolova-Karakashian M, Palmer H, Beharka A, Paulson KE, Meydani SN (2002) Ceramide mediates age-associated increase in macrophage cyclooxygenase-2 expression. J Biol Chem 277:30784–30791. doi: 10.1074/jbc.M204463200 PubMedGoogle Scholar
  21. Coen PM, Dube JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FGS, Goodpaster BH (2010) Insulin resistance is associated with higher intramyocellular triglycerides in type i but not type ii myocytes concomitant with higher ceramide content. Diabetes 59:80–88. doi: 10.2337/db09-0988 PubMedCentralPubMedGoogle Scholar
  22. Coen PM et al (2013) Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity (Silver Spring, Md). doi: 10.1002/oby.20381
  23. Cree MG et al (2004) Intramuscular and liver triglycerides are increased in the elderly. J Clin Endocrinol Metab 89:3864–3871. doi: 10.1210/jc.2003-031986 PubMedGoogle Scholar
  24. Cronan JE (1997) In vivo evidence that acyl coenzyme a regulates DNA binding by the Escherichia coli FadR global transcription factor. J Bacteriol 179:1819–1823PubMedCentralPubMedGoogle Scholar
  25. Defronzo RA (1981) Glucose-intolerance and aging. Diabetes Care 4:493–501. doi: 10.2337/diacare.4.4.493 PubMedGoogle Scholar
  26. DeNino WF, Tchernof A, Dionne IJ, Toth MJ, Ades PA, Sites CK, Poehlman ET (2001) Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care 24:925–932. doi: 10.2337/diacare.24.5.925 PubMedGoogle Scholar
  27. Dube JJ, Amati F, Stefanovic-Racic M, Toledo FGS, Sauers SE, Goodpaster BH (2008) Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete’s paradox revisited. Am JPhysiol-Endocrinol Metab 294:E882–E888. doi: 10.1152/ajpendo.00769.2007 Google Scholar
  28. Ellis BA, Poynten A, Lowy AJ, Furler SM, Chisholm DJ, Kraegen EW, Cooney GJ (2000) Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. Am JPhysiol-Endocrinol Metab 279:E554–E560Google Scholar
  29. Fan J-G, Farrell GC (2009) Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol 50:204–210. doi: 10.1016/j.jhep.2008.10.010 PubMedGoogle Scholar
  30. Fantin F et al (2013) Central and peripheral fat and subclinical vascular damage in older women. Age Ageing 42:359–365. doi: 10.1093/ageing/aft005 PubMedGoogle Scholar
  31. Feng Y, Cronan JE (2009) A New Member of the Escherichia coli fad Regulon: transcriptional Regulation of fadM (ybaW). J Bacteriol 191:6320–6328. doi: 10.1128/jb.00835-09 PubMedCentralPubMedGoogle Scholar
  32. Flannery C, Dufour S, Rabol R, Shulman GI, Petersen KF (2012) Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly. Diabetes 61:2711–2717. doi: 10.2337/db12-0206 PubMedCentralPubMedGoogle Scholar
  33. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging: an evolutionary perspective on immunosenescence. Mol Cell Gerontol 908:244–254Google Scholar
  34. Frisard MI et al (2007) Aging, resting metabolic rate, and oxidative damage; results from the Louisiana healthy aging study. J Gerontol Ser A-Biol Sci Med Sci 62:752–759Google Scholar
  35. Frith J, Day CP, Henderson E, Burt AD, Newton JL (2009) Non-alcoholic fatty liver disease in older people. Gerontology 55:607–613. doi: 10.1159/000235677 PubMedGoogle Scholar
  36. Fuke Y, Okabe S, Kajiwara N, Suastika K, Budhiarta AAG, Maehata S, Taniguchi H (2007) Increase of visceral fat area in Indonesians and Japanese with normal BMI. In: 13th Korea-Japan Symposium on Diabetes Mellitus, Seoul, SOUTH KOREA, Nov 11–12 Sep 2005. pp S224-S227. doi: 10.1016/j.diabres.2007.01.062
  37. Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A (2013) Non-alcoholic fatty liver disease (nafld) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5:1544–1560. doi: 10.3390/nu5051544 PubMedCentralPubMedGoogle Scholar
  38. Gao D, Bailey CJ, Griffiths HR (2009) Metabolic memory effect of the saturated fatty acid, palmitate, in monocytes. Biochem Biophys Res Commun 388:278–282. doi: 10.1016/j.bbrc.2009.07.160 PubMedGoogle Scholar
  39. Gao D, Pararasa C, Dunston CR, Bailey CJ, Griffiths HR (2012) Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis. Free Rad Biol Med 53:796–806. doi: 10.1016/j.freeradbiomed.2012.05.026 PubMedGoogle Scholar
  40. Giusto NM, Roque ME, Deboschero MGI (1992) Effects of aging on the content composition and synthesis of sphingomyelin in the central-nervous-system. Lipids 27:835–839. doi: 10.1007/bf02535859 PubMedGoogle Scholar
  41. Goodpaster BH et al (2005) Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Int Med 165:777–783Google Scholar
  42. Gumbiner B, Thorburn AW, Ditzler TM, Bulacan F, Henry RR (1992) Role of impaired intracellular glucose-metabolism in the insulin resistance of aging. Metab-Clin Exp 41:1115–1121PubMedGoogle Scholar
  43. Guo W et al (2007a) Aging results in paradoxical susceptibility of fat cell progenitors to lipotoxicity. Am J Physiol-Endocrinol Metab 292:E1041–E1051. doi: 10.1152/ajpendo.00557.2006 PubMedGoogle Scholar
  44. Guo W, Wong S, Xie W, Lei T, Luo Z (2007b) Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol-Endocrinol Metab 293:E576–E586. doi: 10.1152/ajpendo.00523.2006
  45. Hansen T, Ahlstrom H, Soderberg S, Hulthe J, Wikstrom J, Lind L, Johansson L (2009) Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population. Atherosclerosis 205:163–167. doi: 10.1016/j.atherosclerosis.2008.11.007
  46. Harman-Boehm I et al (2007) Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92:2240–2247. doi: 10.1210/jc.2006-1811 PubMedGoogle Scholar
  47. Heitmann BL, Frederiksen P (2009) Thigh circumference and risk of heart disease and premature death: prospective cohort study. Br Med J 339. doi: 10.1136/bmj.b3292 Google Scholar
  48. Heshka S et al (2008) Altered body composition in type 2 diabetes mellitus. Int J Obes 32:780–787. doi: 10.1038/sj.ijo.0803802 Google Scholar
  49. Hilton TN, Tuttle LJ, Bohnert KL, Mueller MJ, Sinacore DR (2008) Excessive adipose tissue infiltration in skeletal muscle in individuals with obesity, diabetes mellitus, and peripheral neuropathy: association with performance and function. Phys Ther 88:1336–1344. doi: 10.2522/ptj.20080079 PubMedCentralPubMedGoogle Scholar
  50. Houmard JA et al (1995) Skeletal-muscle glut4 protein-concentration and aging in humans. Diabetes 44:555–560PubMedGoogle Scholar
  51. Houmard JA, Tanner CJ, Yu CL, Cunningham PG, Pories WJ, MacDonald KG, Shulman GI (2002) Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty Acyl-CoAs in morbidly obese subjects. Diabetes 51:2959–2963PubMedGoogle Scholar
  52. Hu G et al (2011) Trunk versus extremity adiposity and cardiometabolic risk factors in white and African American adults. Diabetes Care 34:1415–1418. doi: 10.2337/dc10-2019 PubMedCentralPubMedGoogle Scholar
  53. Huang S et al (2012) Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. In: J Lipid Res, vol 53. vol 9. United States, pp 2002–2013. doi:  10.1194/jlr.D029546
  54. Hube F, Hauner H (1999) The role of TNF-alpha in human adipose tissue: prevention of weight gain at the expense of insulin resistance? Horm Metab Res 31:626–631PubMedGoogle Scholar
  55. Hughes VA, Roubenoff R, Wood M, Frontera WR, Evans WJ, Singh MAF (2004) Anthropometric assessment of 10-year changes in body composition in the elderly. Am J Clin Nutr 80:475–482PubMedGoogle Scholar
  56. Ishikawa M et al (2014) Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects’ gender and age. PLoS ONE 9:e91806. doi: 10.1371/journal.pone.0091806 PubMedCentralPubMedGoogle Scholar
  57. Itani SI, Pories WJ, MacDonald KG, Dohm GL (2001) Increased protein kinase C theta in skeletal muscle of diabetic patients. Metab-Clin Exp 50:553–557PubMedGoogle Scholar
  58. Itani SI, Ruderman NB, Schmieder F, Boden G (2002) Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and I kappa B-alpha. Diabetes 51:2005–2011PubMedGoogle Scholar
  59. Jerschow E, Anwar S, Barzilai N, Rosenstreich D (2007) Macrophages accumulation in visceral and subcutaneous adipose tissue correlates with age. J Allergy Clin Immunol 119:S179–S179. doi: 10.1016/j.jaci.2006.12.066 Google Scholar
  60. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2:165–171PubMedGoogle Scholar
  61. Kagansky N et al (2004) Non-alcoholic fatty liver disease: a common and benign finding in octogenarian patients. Liver Int 24:588–594. doi: 10.1111/j.1478-3231.2004.0969.x PubMedGoogle Scholar
  62. Kajkenova O et al (1997) Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia. J Bone Miner Res 12:1772–1779PubMedGoogle Scholar
  63. Karagiannides I et al (2001) Altered expression of C/EBP family members results in decreased adipogenesis with aging. Am J Physiol-Regul Integr Comp Physiol 280:R1772–R1780PubMedGoogle Scholar
  64. Karagiannides I et al (2006) Increased CUG triplet repeat-binding protein-1 predisposes to impaired adipogenesis with aging. J Biol Chem 281:23025–23033. doi: 10.1074/jbc.M513187200 PubMedGoogle Scholar
  65. Kelley DE, Mandarino LJ (2000) Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677–683PubMedGoogle Scholar
  66. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB (1995) The expression of tumor-necrosis-factor in human adipose-tissue: regulation by obesity, weight-loss, and relationship to lipoprotein-lipase. J Clin Investig 95:2111–2119. doi: 10.1172/jci117899 PubMedCentralPubMedGoogle Scholar
  67. Kim JK et al (2001) Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci USA 98:7522–7527PubMedCentralPubMedGoogle Scholar
  68. Kim DJ, Bergstrom J, Barrett-Connor E, Laughlin GA (2008) Visceral adiposity and subclinical coronary artery disease in elderly adults: rancho Bernardo study. Obesity 16:853–858. doi: 10.1038/oby.2008.15 PubMedCentralPubMedGoogle Scholar
  69. Kirkland JL, Tchkonia T, Pirtskhalava T, Han JR, Karagiannides I (2002) Adipogenesis and aging: does aging make fat go MAD? Exp Gerontol 37:757–767PubMedGoogle Scholar
  70. Krebs M, Roden M (2005) Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature. Diabetes Obes Metab 7:621–632. doi: 10.1111/j.1463-1326.2004.00439.x PubMedGoogle Scholar
  71. Krems C, Luhrmann PM, Strassburg A, Hartmann B, Neuhauser-Berthold M (2005) Lower resting metabolic rate in the elderly may not be entirely due to changes in body composition. Eur J Clin Nutr 59:255–262. doi: 10.1038/sj.ejcn.1602066 PubMedGoogle Scholar
  72. Kuk JL, Lee S, Heymsfield SB, Ross R (2005) Waist circumference and abdominal adipose tissue distribution: influence of age and sex. Am J Clin Nutr 81:1330–1334PubMedGoogle Scholar
  73. Kuk JL, Saunders TJ, Davidson LE, Ross R (2009) Age-related changes in total and regional fat distribution. Ageing Res Rev 8:339–348PubMedGoogle Scholar
  74. Laybutt DR, Schmitz-Peiffer C, Saha AK, Ruderman NB, Biden TJ, Kraegen EW (1999) Muscle lipid accumulation and protein kinase C activation in the insulin-resistant chronically glucose-infused rat. Am J Physiol-Endocrinol Metab 277:E1070–E1076Google Scholar
  75. Lee JY, Sohn KH, Rhee SH, Hwang D (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through toll-like receptor 4. J Biol Chem 276:16683–16689. doi: 10.1074/jbc.M011695200 PubMedGoogle Scholar
  76. Lee M, Choh AC, Demerath EW, Towne B, Siervogel RM, Czerwinski SA (2012a) Associations between trunk, leg and total body adiposity with arterial stiffness. Am J Hypertens 25:1131–1137. doi: 10.1038/ajh.2012.92 PubMedCentralPubMedGoogle Scholar
  77. Lee Y et al (2012b) Comparison of regional body composition and its relation with cardiometabolic risk between BMI-matched young and old subjects. Atherosclerosis 224:258–265. doi: 10.1016/j.atherosclerosis.2012.07.013 PubMedGoogle Scholar
  78. Li H et al (2009) Prevalence and risk factors of fatty liver disease in Chengdu, Southwest China. Hepatobiliary & Pancreatic Dis Int 8:377–382Google Scholar
  79. Li CY, Ford ES, Zhao GX, Kahn HS, Mokdad AH (2010) Waist-to-thigh ratio and diabetes among US adults: the third national health and nutrition examination survey. Diabetes Res Clin Pract 89:79–87. doi: 10.1016/j.diabres.2010.02.014 PubMedGoogle Scholar
  80. Li X et al (2012) Liver fat content is associated with increased carotid atherosclerosis in a Chinese middle-aged and elderly population: the Shanghai Changfeng study. Atherosclerosis 224:480–485. doi: 10.1016/j.atherosclerosis.2012.07.002 PubMedGoogle Scholar
  81. Lightle SA, Oakley JI, Nikolova-Karakashian MN (2000) Activation of sphingolipid turnover and chronic generation of ceramide and sphingosine in liver during aging. Mech Ageing Dev 120:111–125. doi: 10.1016/s0047-6374(00)00191-3 PubMedGoogle Scholar
  82. Lim S et al (2009) Fat in liver/muscle correlates more strongly with insulin sensitivity in rats than abdominal fat. Obesity 17:188–195PubMedGoogle Scholar
  83. Lin JL et al (1991) Altered expression of glucose transporter isoforms with aging in rats: selective decrease in glut4 in the fat tissue and skeletal-muscle. Diabetologia 34:477–482PubMedGoogle Scholar
  84. Liney GP, Bernard CP, Manton DJ, Turnbull LW, Langton CM (2007) Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla. J Magn Reson Imaging 26:787–793. doi: 10.1002/Jmri.21072 PubMedGoogle Scholar
  85. Lio D et al (2002) Gender-specific association between-1082 IL-10 promoter polymorphism and longevity. Genes Immun 3:30–33. doi: 10.1038/sj/gene/6363827 PubMedGoogle Scholar
  86. Little JP, Madeira JM, Klegeris A (2012) The saturated fatty acid palmitate induces human monocytic cell toxicity toward neuronal cells: exploring a possible link between obesity-related metabolic impairments and neuroinflammation. J Alzheimers Dis 30:S179–S183. doi: 10.3233/jad-2011-111262 PubMedGoogle Scholar
  87. Liu C-C et al (2010) Age-related differences in the clinical presentation, associated metabolic abnormality, and estimated cardiovascular risks from nonalcoholic fatty liver disease: a cross-sectional study from health evaluation center in Taiwan. Int J Gerontol 4:184–191. doi: 10.1016/j.ijge.2010.11.005 Google Scholar
  88. Machann J et al (2005) Age and gender related effects on adipose tissue compartments of subjects with increased risk for type 2 diabetes: a whole body MRI/MRS study. Magn Reson Mater Phys Biol Med 18:128–137. doi: 10.1007/s10334-005-0401-x
  89. Marcus RL, Addison O, Kidde JP, Dibble LE, Lastayo PC (2010) Skeletal muscle fat infiltration: impact of age, inactivity, and exercise. J Nutr Health Aging 14:362–366. doi: 10.1007/s12603-010-0081-2 PubMedCentralPubMedGoogle Scholar
  90. Marcus RL, Addison O, LaStayo PC (2013) Intramuscular adipose tissue attenuates gains in muscle quality in older adults at high risk for falling. A brief report. J Nutr Health Aging 17:215–218. doi: 10.1007/s12603-012-0377-5 PubMedGoogle Scholar
  91. Mata P et al (1996) Effect of dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro. Arterioscler Thromb Vasc Biol 16:1347–1355PubMedGoogle Scholar
  92. Mazzali G et al (2006) Interrelations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance: effect of moderate weight loss in older women. Am J Clin Nutr 84:1193–1199PubMedGoogle Scholar
  93. McLaughlin T, Lamendola C, Liu A, Abbasi F (2011) Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab 96:E1756–E1760. doi: 10.1210/jc.2011-0615 PubMedCentralPubMedGoogle Scholar
  94. Miljkovic I et al (2009) Greater adipose tissue infiltration in skeletal muscle among older men of African ancestry. J Clin Endocrinol Metab 94:2735–2742. doi: 10.1210/jc.2008-2541 PubMedCentralPubMedGoogle Scholar
  95. Montell E et al (2001) DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells. Am J Physiol-Endocrinol Metab 280:E229–E237PubMedGoogle Scholar
  96. Morin CL, Pagliassotti MJ, Windmiller D, Eckel RH (1997) Adipose tissue-derived tumor necrosis factor-alpha activity is elevated in older rats. J Gerontol Ser A-Biol Sci Med Sci 52:B190–B195Google Scholar
  97. Morin CL, Gayles EC, Podolin DA, Wei YR, Xu MM, Pagliassotti MJ (1998) Adipose tissue-derived tumor necrosis factor activity correlates with fat cell size but not insulin action in aging rats. Endocrinology 139:4998–5005PubMedGoogle Scholar
  98. Nicklas BJ et al (2006) Abdominal obesity is an independent risk factor for chronic heart failure in older people. J Am Geriatr Soc 54:413–420. doi: 10.1111/j.1532-5415.2005.00624.x PubMedGoogle Scholar
  99. Ohanian J, Liao A, Forman SP, Ohanian V (2014) Age-related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long-chain ceramides. Physiol Rep 2. doi: 10.14814/phy2.12015
  100. Park JS, Cho MH, Ahn CW, Kim KR, Huh KB (2012) The association of insulin resistance and carotid atherosclerosis with thigh and calf circumference in patients with type 2 diabetes. Cardiovasc Diabetol 11:8. doi: 10.1186/1475-2840-11-62 Google Scholar
  101. Perez GI et al (2005) A central role for ceramide in the age-related acceleration of apoptosis in the female germline. Faseb J 19:860–862. doi: 10.1096/fj.04-2903fje
  102. Permana PA, Menge C, Reaven PD (2006) Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun 341:507–514. doi: 10.1016/j.bbrc.2006.01.012 PubMedGoogle Scholar
  103. Perseghin G et al (2008) Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver. Hepatology 47:51–58PubMedGoogle Scholar
  104. Petersen KF et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142PubMedCentralPubMedGoogle Scholar
  105. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671PubMedCentralPubMedGoogle Scholar
  106. Pickersgill L, Litherland GJ, Greenberg AS, Walker M, Yeaman SJ (2007) Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem 282:12583–12589. doi: 10.1074/jbc.M611157200 PubMedGoogle Scholar
  107. Pilz S et al (2006) Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab 91:2542–2547. doi: 10.1210/jc.2006-0195 PubMedGoogle Scholar
  108. Qu X, Seale JP, Donnelly R (1999a) Tissue and isoform-selective activation of protein kinase C in insulin-resistant obese Zucker rats: effects of feeding. J Endocrinol 162:207–214PubMedGoogle Scholar
  109. Qu XQ, Seale JP, Donnelly R (1999b) Tissue- and isoform-specific effects of aging in rats on protein kinase C in insulin-sensitive tissues. Clin Sci 97:355–361PubMedGoogle Scholar
  110. Racette SB, Evans EM, Weiss EP, Hagberg JM, Holloszy JO (2006) Abdominal adiposity is a stronger predictor of insulin resistance than fitness among 50–95 year olds. Diabetes Care 29:673–678PubMedGoogle Scholar
  111. Rivas DA et al (2012) Increased ceramide content and NF kappa B signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males. J Appl Physiol 113:1727–1736. doi: 10.1152/japplphysiol.00412.2012 PubMedCentralPubMedGoogle Scholar
  112. Rodriguez-Calvo R et al (2007) Peroxisome proliferator-activated receptor alpha down-regulation is associated with enhanced ceramide levels in age-associated cardiac hypertrophy. J Gerontol Ser A-Biol Sci Med Sci 62:1326–1336Google Scholar
  113. Rosen CJ, Bouxsein ML (2006) Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2:35–43PubMedGoogle Scholar
  114. Rosen CJ, Ackert-Bicknell C, Rodriguez JP, Pino AM (2009) Marrow Fat and the Bone Microenvironment: developmental, Functional, and Pathological Implications. Crit Rev Eukaryot Gene Expr 19:109–124PubMedCentralPubMedGoogle Scholar
  115. Sakuma K, Yamaguchi A (2010) Molecular mechanisms in aging and current strategies to counteract sarcopenia. Curr Aging Sci 3:90–101PubMedGoogle Scholar
  116. Samuel VT, Petersen KF, Shulman GI (2010) Lipid-induced insulin resistance: unravelling the mechanism. Lancet 375:2267–2277PubMedCentralPubMedGoogle Scholar
  117. Schrauwen-Hinderling VB et al (2005) Iramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet. Obes Res 13:2088–2094PubMedGoogle Scholar
  118. Schwartz EA et al (2010) Nutrient modification of the innate immune response a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation. Arterioscler Thromb Vasc Biol 30:802–808. doi: 10.1161/atvbaha.109.201681 PubMedGoogle Scholar
  119. Schwenzer NF, Martirosian P, Machann J, Schraml C, Steidle G, Claussen CD, Schick F (2009) aging effects on human calf muscle properties assessed by MRI at 3 tesla. J Magn Reason Imaging 29:1346–1354. doi: 10.1002/jmri.21789 Google Scholar
  120. Shay CM, Secrest AM, Goodpaster BH, Kelsey SF, Strotmeyer ES, Orchard TJ (2010) Regional adiposity and risk for coronary artery disease in type 1 diabetes: does having greater amounts of gluteal-femoral adiposity lower the risk? Diabetes Res Clin Pract 89:288–295. doi: 10.1016/j.diabres.2010.03.028 PubMedCentralPubMedGoogle Scholar
  121. Silaghi A et al (2008) Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy. Obesity 16:2424–2430. doi: 10.1038/oby.2008.379 PubMedGoogle Scholar
  122. Skovbro M, Baranowski M, Skov-Jensen C, Flint A, Dela F, Gorski J, Helge JW (2008) Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity. Diabetologia 51:1253–1260. doi: 10.1007/s00125-008-1014-z PubMedGoogle Scholar
  123. Slawik M, Vidal-Puig AJ (2006) Lipotoxicity, overnutrition and energy metabolism in aging. Ageing Res Rev 5:144–164. doi: 10.1016/j.arr.2006.03.004 PubMedGoogle Scholar
  124. Solomon TPJ, Marchetti CM, Krishnan RK, Gonzalez F, Kirwan JP (2008) Effects of aging on basal fat oxidation in obese humans. Metab Clin Exp 57:1141–1147. doi: 10.1016/j.metabol.2008.03.021 PubMedCentralPubMedGoogle Scholar
  125. Starr ME, Evers BM, Saito H (2009) Age-associated increase in cytokine production during systemic inflammation: adipose tissue as a major source of IL-6. J Gerontol Ser A-Biol Sci Med Sci 64:723–730 doi: 10.1093/gerona/glp046
  126. Stephens JM, Pekala PH (1992) Transcriptional repression of the C/Ebp-alpha and Glut4 genes In 3t3-L1 adipocytes by tumor-necrosis-factor-alpha: regulation is coordinate and independent of protein-synthesis. J Biol Chem 267:13580–13584PubMedGoogle Scholar
  127. St-Onge MP, Gallagher D (2010) Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition 26:152–155. doi: 10.1016/j.nut.2009.07.004 PubMedCentralPubMedGoogle Scholar
  128. Suganami T, Nishida J, Ogawa Y (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25:2062–2068. doi: 10.1161/01.atv.0000183883.72263.13 PubMedGoogle Scholar
  129. Suganami T et al (2007) Role of the Toll-like receptor 4/NF-kappa B pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27:84–91. doi: 10.1161/01.ATV.0000251608.09329.9a
  130. Sutton-Tyrrell K et al (2001) Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition. Hypertension 38:429–433PubMedGoogle Scholar
  131. Takahashi K et al (2008) JNK- and I kappa B-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro. Am J Physiol-Endocrinol Metab 294:E898–E909. doi: 10.1152/ajpendo.00131.2007
  132. Takamura T, Misu H, Ota T, Kaneko S (2012) Fatty liver as a consequence and cause of insulin resistance: lessons from type 2 diabetic liver. Endocr J 59:745–763PubMedGoogle Scholar
  133. Tchkonia T, Wise B, Chan G, Karagiannides I, Kirkland JL (2001) Aging, CHOP expression, and preadipocyte differentiation. Obes Res 9:147S–147SGoogle Scholar
  134. Tchkonia T et al (2007) Increased TNF alpha and CCAAT/enhancer-binding protein homologous protein with aging predispose preadipocytes to resist adipogenesis. Am J Physiol-Endocrinol Metab 293:E1810–E1819. doi: 10.1152/ajpendo.00295.2007 PubMedGoogle Scholar
  135. Thompson AL, Cooney GJ (2000) Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 49:1761–1765PubMedGoogle Scholar
  136. Tiikkainen M et al (2002) Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes. Obes Res 10:859–867PubMedGoogle Scholar
  137. Tomas E et al (2002) Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 99:16309–16313. doi: 10.1073/pnas.222657499
  138. Tsintzas K, Chokkalingam K, Jewell K, Norton L, Macdonald IA, Constantin-Teodosiu D (2007) Elevated free fatty acids attenuate the insulin-induced suppression of PDK4 gene expression in human skeletal muscle: potential role of intramuscular long-chain acyl-coenzyme a. J Clin Endocrinol Metab 92:3967–3972. doi: 10.1210/jc.2007-1104 PubMedGoogle Scholar
  139. Ueno K et al (2009) Increased epicardial fat volume quantified by 64-multidetector computed tomography is associated with coronary atherosclerosis and totally occlusive lesions. Circ J 73:1927–1933PubMedGoogle Scholar
  140. van der Meer RW et al (2008) The ageing male heart: myocardial triglyceride content as independent predictor of diastolic function. Eur Heart J 29:1516–1522. doi: 10.1093/eurheartj/ehn207 PubMedGoogle Scholar
  141. van Harmelen V, Rohrig K, Hauner H (2004) Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metab Clin Exp 53:632–637. doi: 10.1016/j.metabol.2003.11.012 PubMedGoogle Scholar
  142. van Loon LJC, Goodpaster BH (2006) Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state. Pflugers Archiv-Eur J Physiol 451:606–616. doi: 10.1007/s00424-005-1509-0 Google Scholar
  143. Van Pelt RE, Jankowski CM, Gozansky WS, Wolfe P, Schwartz RS, Kohrt WM (2011) Sex differences in the association of thigh fat and metabolic risk in older adults. Obesity 19:422–428. doi: 10.1038/oby.2010.140 PubMedCentralPubMedGoogle Scholar
  144. Venable ME, Webb-Froehlich LM, Sloan EF, Thomley JE (2006) Shift in sphingolipid metabolism leads to an accumulation of ceramide in senescence. Mech Ageing Dev 127:473–480. doi: 10.1016/j.mad.2006.01.003 PubMedGoogle Scholar
  145. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig 112:1796–1808. doi: 10.1172/jci2000319246 PubMedCentralPubMedGoogle Scholar
  146. Wu ZD et al (1999) Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell 3:151–158PubMedGoogle Scholar
  147. Wu D, Ren Z, Pae M, Guo W, Cui X, Merrill AH, Meydani SN (2007) Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J Immunol 179:4829–4839PubMedGoogle Scholar
  148. Wu HY et al (2010) Independent and opposite associations of trunk and leg fat depots with adipokines, inflammatory markers, and metabolic syndrome in middle-aged and older chinese men and women. J Clin Endocrinol Metab 95:4389–4398. doi: 10.1210/jc.2010-0181 PubMedGoogle Scholar
  149. Yaney GC, Korchak HM, Corkey BE (2000) Long-chain acyl CoA regulation of protein kinase C and fatty acid potentiation of glucose-stimulated insulin secretion in clonal beta-cells. Endocrinology 141:1989–1998PubMedGoogle Scholar
  150. Yim JE, Heshka S, Albu J, Heymsfield S, Kuznia P, Harris T, Gallagher D (2007) Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk. Int J Obes 31:1400–1405. doi: 10.1038/sj.ijo.0803621 Google Scholar
  151. Youm Y-H et al (2012) The NLRP3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Rep 1:56–68. doi: 10.1016/j.celrep.2011.11.005
  152. Yu CL et al (2002) Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 277:50230–50236PubMedGoogle Scholar
  153. Zamboni M et al (2003) Body composition changes in stable-weight elderly subjects: the effect of sex. Aging Clin Exp Res 15:321–327PubMedGoogle Scholar
  154. Zhang B, Berger J, Hu EI, Szalkowski D, WhiteCarrington S, Spiegelman BM, Moller DE (1996) Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Mol Endocrinol 10:1457–1466PubMedGoogle Scholar
  155. Zhang WY, Schwartz E, Wang YJ, Attrep J, Li Z, Reaven P (2006) Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells. Arterioscler Thromb Vasc Biol 26:514–519. doi: 10.1161/01.atv.0000200226.53994.09
  156. Zhou Q, Du J, Hu Z, Walsh K, Wang XH (2007) Evidence for adipose-muscle cross talk: opposing regulation of muscle proteolysis by adiponectin and fatty acids. Endocrinology 148:5696–5705. doi: 10.1210/en.2007-0183 PubMedGoogle Scholar
  157. Zuo Y, Qiang L, Farmer SR (2006) Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter. J Biol Chem 281:7960–7967. doi: 10.1074/jbc.M510682200 PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Chathyan Pararasa
    • 1
    Email author
  • Clifford J. Bailey
    • 1
  • Helen R. Griffiths
    • 1
  1. 1.School of Life and Health Science and Aston Research Centre for Healthy AgeingAston UniversityBirminghamUK

Personalised recommendations