Aspetto morfologico ed immunoistochimico dell’infiltrato macrofagico e linfocitario del tessuto adiposo periaortico; microscopio ottico. Aspetto dei vasi capillari osservati AOAT; all’interno del vaso si possono apprezzare diversi tipi di cellule infiammatorie: linfociti, eosinofili, monociti; ematossilina ed eosina 40x “ Crown like structure”; macrofagi circondanti un adipocita; PLP ed ematossilina 100x Aggregato linfocitario; ematossilina ed eosina 40x Aggregato linfocitario; PLP ed ematossilina 100x
Heat Shock proteins HSPs sono molecole chaperones che facilitano un corretto folding proteico. GRP78 (glucose-regulated protein 78) ne fa parte. Principalmente nell’ER , dove partecipa alla disgregazione di proteine con folding irreversibilmente errato ed eventualmente all’avvio di meccanismi proapoptotici. iROS sembrano essere tra i principali attivatori (es condizioni pre-ischemiche che aumentano ROS nella fase di riperfusione danno aumento di GRP78) GRP75 fa parte della stessa famiglia e viene espresso principalmente a livello mitocondriale. In questi vetrini si ha la colorazione immunoistochimica più la controcolorazione in ematossilina In quest’immagine non si evidenzia un gradiente nei miocardiociti verso gli adipociti, ma quello che sottolineava Corsetti era la positività intensa del citoplasma di alcuni adipociti a marcatori di stress
Paziente dislipidemico iperteso 75 anni 29,5BMI non coronaropatico Importante fibrosi intorno agli adipociti intramiocardici Corsetti faceva notare nella seconda immagine del GRP-78 positività di fibroblasti vicino agli adipociti.
Logistic regression analysis. Figure 1 shows the observed percentages of subjects with worsening in FEV1 according to FFM and SAD status. Patients who had decreased FFM/increased SAD and subjects who had stable FFM/decreased SAD showed a probability of having a worsening in FEV1 of 80% (observed 12 out of 15) and 22.2% respectively (observed: 4 out of 18).
Sarcopenic Obesity Prof Mauro Zamboni Department of Medicine-Geriatric Division University of Verona-Italy 4 ST International Seminar on Preventive Geriatrics Athens April 1 st -3 rd 2011
Sarcopenic Obesity R Roubenoff, 2004 Epidemic of Obesity
Prevalence of Obesity and Overweight for Adults Aged 20 Years or Older Flegal, K. M. et al. 2010;303:235-241
BMI underweight normalweight overweight obesity morbid obesity < 18.5 18.5-25 25-30 > 30 >40 WHO, 1998 weight (kg) height (m) 2 BMI = Obesity should be identified as the degree of fat storage associated with elevated health risk. The practical definition of Obesity is based on BMI
Sarcopenic Obesity Epidemic of Obesity Aging of the population Age related body composition changes
Age related increase in body fat for normal males at constant body mass index (BMI) Body fat (%) Body weight (kg) Age (years) Prentice AM & Jebb SA, 2001
Age-related decreases in thigh muscle area, knee extensor strenght, and aerobic capacity in 78 healthy persons Nair KS, Am J Clin Nutr 2005
Normal Obese Sarcopenic Sarcopenic Obese 5.0 6.0 7.0 Relative Muscle Mass (kg/m2) 20 30 40 % Body Fat Median -2 SD below Young adult mean Baumgartner, 2000 Body composition in healthy aging: the New Mexico Elder Health Survey and the New Mexico Aging Process Study Definition of Sarcopenic Obesity Sarcopenia Muscle mass/ height squared less than -2SD below the young adult mean Sarcopenic obesity Muscle mass/ height squared less than -2SD below the young adult reference mean with % Fat > 27 in men and 38 in women or BMI > 30
Prevalences of obesity, sarcopenia and sarcopenic-obesity by age in the combined New Mexico Elder Health Survey and New Mexico Aging Process Study % <70 y 70-74 y 75-79 y >80 y Obese Normal Sarcopenic Sarcopenic-Obese Baumgartner et al, 1998
Comparison of different sarcopenic obesity definitions and prevalences * Age and gender adjusted prevalence. † Standard error Stenholm Curr Opin Clin Nutr Metab Care 2008 Definition of sarcopenic obesity N Mean age (SD) Prevalence* New Mexico Aging Process Study <ul><li>Sarcopenia: skeletal muscle mass -2 SD below mean of young population or < 7.26 kg/m 2 in men and < 5.45 kg/m 2 in women. </li></ul><ul><li>Obesity: percentage body fat greater than median or > 27% in men and 38% in women. </li></ul>831 60 and over M: 4.4% F: 3.0% NHANES III <ul><li>Sarcopenia: two lower quintiles of muscle mass (<9.12 kg/m 2 in men and <6.53 kg/m 2 in women) </li></ul><ul><li>Obesity: two highest quintiles of fat mass (>37.16% in men and > 40.01% in women). </li></ul>M: 1391 F: 1591 M: 76.3 (1.7 † ) F: 77.3 (2.2 † ) M: 9.6% F: 7.4% Zoico et al <ul><li>Sarcopenia: two lower quintiles of muscle mass (<5.7 kg/m 2 ) </li></ul><ul><li>Obesity: two highest quintiles of fat mass (>42.9%) </li></ul>F: 167 71.7 (2.4) F: 12.4%
a potential problems with definition of Sarcopenic Obesity: Quantity or Quality of fat free mass and fat mass ?
Loss of leg lean mass and muscle strength in older Results from the Health, Aging and Body Composition Study Goodpaster et al. J Gerontol Med Sci, 2006 Definition based on hand grip strength (instead of muscle mass) and BMI in four epidemiological studies gives a prevalence of Sarcopenic Obesity between 4-9%
With Sarcopenic Obesity increases in Intermuscular Fat and Intramuscular fat: Low Density Lean Tissue by CT
kilograms of adipose Visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) increase with age Men Women Gallagher et al., 2004
Body fat changes and ectopic fat deposition in the elderly Abdominal subcutaneous fat Hepatic and pancreatic fat Abdominal visceral AT Epicardial fat, perivascular fat Subcutaneous fat Lower body If loss of muscle mass or strength Sarcopenic obesity Inter-intra muscular fat
<ul><li>Muscle-Fat </li></ul><ul><li>a two-way cross-talk ? </li></ul>What is the biological connection between Sarcopenia and Obesity?
Nair KS, 2005 Does muscle loss cause fat gain ?
Adipose tissue Pro-inflammatory cytokines Pathways to sarcopenia ? Does Fat gain cause Muscle loss? Anti-inflammatory cytokines
Man 79 years BMI 35.21 Kg/m ² Obese sarcopenic subject Normal weight subject
80 years BMI 26 Kg/m² 79 years BMI 35.2 Kg/m² Rossi et al. Obesity 2010 Mar 18
Association between intermuscular adipose tissue area (IMAT), metabolic variables, indices of sistemic and local inflammation in 20 elderly men Insulin HOMA Leptin hs-CRP r 0.55 r 0.49 r 0.76 r 0.40 p<0.05 p<0.001 p<0.01 Zoico E, Zamboni M et al. 2009 IL-6 r 0.11 IL-6 mRNA SAT r 0.50 p<0.05
Subcutaneous AT Peritoneal AT Peri Aortic AT Epicardial AT 35 men aged 65.7±5 with coronary artery diseases or valve diseases
SAT EAT SAT SAT AOAT EAT EAT AOAT AOAT * * Adiponectin MCP-1 CD-3 *=p<0,05 * * * * Bambace et al. Cardiovascular Pathology 2010
Inflammatory cells and pericardial fat macrophages linphocytes University of Verona 2010, to be submitted
Myocardial fatty infiltration University of Verona 2010, to be submitted Human atrium stained with hematoxylin and eosin ; Magnification. A. 10x; B. 20x; Scale bar: A. = 200μm; B.= 100μm 9 subjects of 35 (4 CAD; 5 nonCAD) Age M ± SD 69,55 ± 7.50 years BMI 27.33±1.98 kg/m 2
Myocardial fatty infiltration CAD, MS Age 73, BMI 27 nonCAD, MS Age 78, BMI 27 University of Verona 2010, to be submitted Staining: Perilipin + hematoxylin; Magnification: A.B. 10x ; C. 100x ; D. 40x Scale bar: A. and B.= 200μm; C. = 20μm; D. = 50μm
Grp-75 marker of mithocondrial stress Grp-78 marker of endoplasmatic reticolus stress Grp-75 Grp-78 University of Verona and Brescia. Unpublished
Grp-75 G rp-78 subject 42 University of Verona and Brescia. Unpublished fibrosis
Miosteatosis plus Miofibrosis for muscle quality? University of Verona Unpublished miofibrosis miosteatosis
Obesity acts synergistically with sarcopenia to maximize the risk of physical disability
Associations between purely sarcopenic, purely obese, or sarcopenic-obese subjects and self-reported difficulties with physical function Rolland Y, 2009
Incidence of Sarcopenia and Sarcopenic Obesity (7 year follow-up) % 19% 49% Rossi A et al, 2008
Relative Risk of Pulmonary decline by body composition changes (adjusted by sex and smoking) * p<0.05 OR * * Sarcopenic obese OR=14 Rossi A et al, 2008
Differences in muscle density , muscle area ratio and fat area ratio, according frailty syndrome status 923 subjects, aged 65 years or older The fat frail sarcopenic subject
Risk Falls Fractures Physical Disability Diabetes Hypertension Dyslipidemia CVD Insulin resistance Zamboni et al, 2008 Sarcopenia reduced muscle mass and strenght Obesity mainly visceral obesity
The concept of Sarcopenic Obesity could help us understand the complexity of the relation between obesity, mortality and morbidity in the elderly Better knowledge of the biological connection between sarcopenia and obesity is needed Better definition of sarcopenic obesity is warranted