obesità e tnf alfa
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Sindrome metabolica, obesità e terapia con anti TNF alfa
Luigi Landolfi AOU Medicina Interna Salerno
Il Ruolo del TNF – α nel metabolismo degli adipociti Il Ruolo del TNF – α nel metabolismo degli adipociti
Modula il metabolismo lipidico : Riduce l’uptake dei FFA e
la sintesi dei trigliceridi (lipogenesi)
Incrementa la lipolisi
Il Ruolo del TNF – α nel metabolismo degli adipociti Il Ruolo del TNF – α nel metabolismo degli adipociti
Modula il metabolismo lipidico :
Induce Insulinoresistenza
Il Ruolo del TNF – α nel metabolismo degli adipociti Il Ruolo del TNF – α nel metabolismo degli adipociti
Modula il metabolismo lipidico :
Induce Insulinoresistenza
Regola la produzione di leptina
Il Ruolo del TNF – α nel metabolismo degli adipociti Il Ruolo del TNF – α nel metabolismo degli adipociti
Modula il metabolismo lipidico :
Induce Insulinoresistenza
> Livelli di PAI-1 adipocitari e circolanti
plasminogen activator inhibitor PAI-1.
Il Ruolo del TNF – α nel metabolismo degli adipociti Il Ruolo del TNF – α nel metabolismo degli adipociti
Modula il metabolismo lipidico :
Induce Insulinoresistenza
Potente inibitore della differenziazione degli adipociti
Il Ruolo del TNF – α nel metabolismo degli adipociti Il Ruolo del TNF – α nel metabolismo degli adipociti
Modula il metabolismo lipidico :
Induce Insulinoresistenza
> l’apoptosi nel tessuto adiposo
Obesità Infiammazione e Insulinoresistenza Obesità Infiammazione e Insulinoresistenza
Adipokine expression and secretion by adipose tissue in lean subjects
Obesità Infiammazione e Insulinoresistenza Obesità Infiammazione e Insulinoresistenza
Obese subjects
INFIAMMAZIONE
Adipose tissue inflammation The increase in fat cell size is accompanied by the increased infiltration of immune cells including macrophages (arrows).
Lipidi e mediatori dell’infiammazione : integrazione delle risposte metaboliche e immunitarie in adipociti e macrofagi attraverso meccanismi condivisi
Time course of hypothalamic inflammation after the onset of HFD feeding.
Radiologic evidence of gliosis in the MBH of obese humans
Implications and future directions
This finding advances knowledge about the pathological changes affectingthe central nervous system during the development of metabolic syndrome,and provides support for the idea that hypothalamic neuropathy contributesto the condition.
Inhibition of Hypothalamic Inflammation Reverses Diet-Induced Insulin Resistance in the Liver
Marciane Milanski 1, 2, Ana P. Arruda 1, Andressa Coope 1, Let ícia M. Ignacio-Souza 1, Carla E. Nunez 1, Erika A. Roman 1, Tal i ta Romanatto 1, Livia B. Pascoal 1, Andrea M. Caricil l i 3, Marcio A. Torsoni 1,2, Patr icia O. Prada 2, Mario J. Saad 3 and Licio A. Velloso 1
The inhibition of TLR4 and TNFα in the hypothalamus reduces hypothalamic inflammation and corrects leptin resistance .
Toll-Like Receptors TLR 4
All patients received the same dose of methotrexate during the study as before the study plus four infusions of infliximab (Remicade, Janssen) at a dose of 3 mg per kilogram of body weight at the initiation of treatment (week 0) and at weeks 2, 6 and, 14.
In addition to the anti-inflammatory action, infliximab
• improves insulin sensitivity • alters lipid profile. • reduction in insulin resistance• contributes to the recently reported decreased incidence of cardiovascular events in RA .
Nature Reviews Rheumatology , | doi:10.1038/nrrheum.2012.158
Rheumatoid arthritis: Obesity impairs efficacy of anti-TNF therapy in patients with RA
Miguel A. González-Gay & Carlos González-Juanatey
Pazienti con A.R. : anti-TNF oltre all’effetto antiinfiammatorio migliorano anche la sensibilità all’insulina riducendo l’insulinoresistenza solo nei pazienti con normale BMI .
J Rheumatol. 2014 Jun;41(6):1112-7. doi: 10.3899/jrheum.131150. Epub 2014 Apr 15.
Early increase of abdominal adiposity in patients with spondyloarthritis receiving anti-tumor necrosis factor-α treatment.
Hmamouchi I1, Roux C2, Paternotte S2, Kolta S2, Dougados M2, Briot K2.
J Rheumatol. 2014 Jun;41(6):1112-7. doi: 10.3899/jrheum.131150. Epub 2014 Apr 15.
Early increase of abdominal adiposity in patients with spondyloarthritis receiving anti-tumor necrosis factor-α treatment.
Hmamouchi I1, Roux C2, Paternotte S2, Kolta S2, Dougados M2, Briot K2.
In patients with SpA receiving anti-TNF-α therapy, there is an early significant increase in abdominal obesity with significant increase in both VAT and SAT after 1 and 2 years of treatment.
Prospective studies are required to investigate the relationship between these changes and cardiovascular risk.
Postepy Dermatol Alergol. 2014 Feb;31(1):29-31. doi: 10.5114/pdia.2014.40656. Epub 2014 Feb 25.
Influence of ustekinumab on body weight of patients with psoriasis: an initial report.Owczarczyk-Saczonek A, Placek W, Rybak-d'Obyrn J, Wygonowska E.
Postepy Dermatol Alergol. 2014 Feb;31(1):29-31. doi: 10.5114/pdia.2014.40656. Epub 2014 Feb 25.
Influence of ustekinumab on body weight of patients with psoriasis: an initial report.Owczarczyk-Saczonek A, Placek W, Rybak-d'Obyrn J, Wygonowska E.
Postepy Dermatol Alergol. 2014 Feb;31(1):29-31. doi: 10.5114/pdia.2014.40656. Epub 2014 Feb 25.
Influence of ustekinumab on body weight of patients with psoriasis: an initial report.Owczarczyk-Saczonek A, Placek W, Rybak-d'Obyrn J, Wygonowska E.
Postepy Dermatol Alergol. 2014 Feb;31(1):29-31. doi: 10.5114/pdia.2014.40656. Epub 2014 Feb 25.
Influence of ustekinumab on body weight of patients with psoriasis: an initial report.Owczarczyk-Saczonek A, Placek W, Rybak-d'Obyrn J, Wygonowska E.
Body mass increase was determined in 7 patients (64%), on average by 2.27 kg (p < 0.05), and the BMI increased by 3.35% (p < 0.1).
Rheumatology (Oxford). 2014 May;53(5):875-81. doi: 10.1093/rheumatology/ket433. Epub 2014 Jan 9.
Body weight, gender and response to TNF-α blockers in axial spondyloarthritis.
Gremese E1, Bernardi S, Bonazza S, Nowik M, Peluso G, Massara A, Tolusso B, Messuti L, Miceli MC, Zoli A, Trotta F, Govoni M, Ferraccioli G.
- 170 Pazienti con “active axial SpA” (BASDAI > 4) , - trattati per 12 mesi con anti TNF-α :
adalimumab (ADA), etanercept (ETA), infliximab (IFX)
Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30).
After 12 months of treatment : - a 50% improvement of the initial BASDAI (BASDAI50) was the primary end point - and BASDAI ≤ 1 was the secondary end point.
BASDAIBath Ankylosing SpondylitisDisease Activity Index
1. How would you describe the overall level of fatigue/tiredness you have experienced?
NONE _____________________________________________ VERY SEVERE 2. How would you describe the overall level of AS neck, back or hip pain you have had?
NONE _____________________________________________ VERY SEVERE 3. How would you describe the overall level of pain/swelling in joints other than neck, back, hips you have had?
NONE _____________________________________________ VERY SEVERE 4. How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure?
NONE _____________________________________________ VERY SEVERE 5. How would you describe the overall level of morning stiffness you have had from the time you wake up?
NONE _____________________________________________ VERY SEVERE 6. How long does your morning stiffness last from the time you wake up?
_____________________________________________ 0 hrs ½ 1 1½ 2 or more hours
Rheumatology (Oxford). 2014 May;53(5):875-81. doi: 10.1093/rheumatology/ket433. Epub 2014 Jan 9.
Body weight, gender and response to TNF-α blockers in axial spondyloarthritis.
Gremese E1, Bernardi S, Bonazza S, Nowik M, Peluso G, Massara A, Tolusso B, Messuti L, Miceli MC, Zoli A, Trotta F, Govoni M, Ferraccioli G.
- 170 Pazienti con “active axial SpA” (BASDAI > 4) , - trattati per 12 mesi con anti TNF-α :
adalimumab (ADA), etanercept (ETA), infliximab (IFX)
Minor tasso di successo della terapia
- Nelle donne , in sovrapeso - e soprattutto nelle obese
TNF–α ?Ruolo importante - nella sindrome metabolica - nell’insulinoresistenza- flogosi cronica Rischio metabolico CardiovascolareNeoplastico …
anti TNF–α Sembrano migliorare - la sindrome metabolica - l’insulinoresistenza- la flogosi cronica < Rischio metabolico ? < Cardiovascolare ? < Neoplastico ?
?
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