In case of positive energy balance, a progressive pathological remodeling of the adipose tissues occurs: adipocytes increase their volume leading to a consequent increase of fat mass. Hypertrophy of adipose cells is associated with cellular abnormalities and a massive infiltration of macrophages which induce a state of chronic low-grade inflammation that leads over time to insulin-resistance and eventually type 2 diabetes. Another feature of obesity is remodeling of the extracellular matrix with an excessive accumulation of fibrosis that increases the total stiffness of the obese adipose tissue and reduces expandability of the tissue. Some aspects regarding the development and the progression of fibrosis in adipose tissues in humans remain to be elucidated. In this regard, we performed a systematic study of visceral and subcutaneous fat biopsies from 33 obese patients undergoing bariatric surgery, compared with fat biopsies from 6 lean control patients. We detect that a large percentage of omental and subcutaneous adipocytes are PLIN1-negative, and a positive correlation between the amount of PLIN1-negative adipose cells is found in both adipose depots considered. The amount of non-viable adipose cells is significantly correlated with total fibrosis in all obese patients, in fact PLIN1-negative adipocytes, single or grouped, are surrounded by fibrotic bundles. Pyroptosis, the main mechanism of cell death of murin hypertrophic adipocytes, is not revealed within fibrotic regions. Furthermore, TEM analyses demonstrate that dense collagen fibrils are closely associated to the external surface of basal membrane of adipocytes, more in obese than lean subjects, consistent with hyperproduction of collagen fibrils by adipocytes themselves, and signs of cellular stress in degenerating adipocytes were also found. Finally, data support the idea that a large proportion of hypertrophic adipose cells die, due to hyperproduction of collagen fibrils and they consequently recruit inflammatory cells to clean up the adipose tissue. Macrophages are prevalent mainly in the parenchyma and only to a lesser extent in Crown-like Structures (CLS), unlike the mouse models. They probably induce insulin-resistance, and this could explain the pathogenetic hypothesis of the link between obesity and diabetes. Therefore, in humans we hypothesize that, in addition to death of pyroptosis, there could be another type of cell death for obese adipocytes, related to fibrosis. The clinical significance of this new aspect of the histopathology of adipose tissue in obese people remains to be indagated.
Nei periodi di bilancio energetico positivo si verifica un progressivo rimodellamento patologico dei tessuti adiposi: gli adipociti aumentano il loro volume portando ad un conseguente aumento della massa grassa. L'ipertrofia delle cellule adipose è associata ad anomalie cellulari e ad una massiccia infiltrazione di macrofagi che inducono ad uno stato infiammatorio cronico di basso grado che porta nel tempo all'insulino-resistenza ed infine al diabete mellito di tipo 2. Un altro segno distintivo dell'obesità è il rimodellamento della matrice extracellulare con un eccessivo accumulo di fibrosi che aumenta la rigidità totale e riduce l'espandibilità del tessuto adiposo obeso. Restano da chiarire alcuni aspetti dello sviluppo e della progressione della fibrosi nei tessuti adiposi nell'uomo. A questo proposito, abbiamo eseguito uno studio sistematico di biopsie di grasso viscerale e sottocutaneo di 33 pazienti obesi sottoposti a chirurgia bariatrica, paragonati a biopsie di grasso di 6 pazienti magri, di controllo. Rileviamo che una grande percentuale di adipociti è PLIN1-negativa e, inoltre esiste una correlazione positiva nella quantità di cellule adipose PLIN1-negative in entrambi i depositi adiposi considerati. La quantità di adipociti non vitali è significativamente correlata alla fibrosi totale in tutti i pazienti obesi, infatti gli adipociti PLIN1 negativi, singoli o raggruppati, sono circondati da fasci fibrotici. La piroptosi, il principale meccanismo di morte cellulare degli adipociti ipertrofici murini, non è rilevata nelle regioni fibrotiche. Inoltre, le analisi TEM dimostrano che le fibrille collagene sono strettamente associate alla superficie esterna della membrana basale degli adipociti, maggiormente nei soggetti obesi rispetto ai magri, consistente con l'iperproduzione di fibrille collagene da parte degli stessi adipociti e inoltre sono stati trovati anche segni di stress cellulare negli adipociti in degenerazione. Infine, i dati supportano l'idea che una grande percentuale di cellule adipose ipertrofiche muoia, a causa dell'iperproduzione di fibrille di collagene e di conseguenza vengano reclutate cellule infiammatorie per ripulire il tessuto adiposo. I macrofagi sono presenti principalmente nel parenchima e solo in misura minore nelle Crown-like Structures (CLS), a differenza dei modelli murini. Probabilmente inducono all'insulino-resistenza, e questo potrebbe spiegare l'ipotesi patogenetica del legame tra obesità e diabete. Pertanto, nell'uomo ipotizziamo che, oltre alla morte per piroptosi, possa esserci un altro tipo di morte cellulare per gli adipociti obesi, correlata alla fibrosi. Resta da indagare il significato clinico di questo nuovo aspetto dell'istopatologia del tessuto adiposo nelle persone obese.
Morphology of visceral and subcutaneous adipose tissue of obese subjects / DI VINCENZO, Angelica. - (2021 May 11).
Morphology of visceral and subcutaneous adipose tissue of obese subjects
DI VINCENZO, ANGELICA
2021-05-11
Abstract
In case of positive energy balance, a progressive pathological remodeling of the adipose tissues occurs: adipocytes increase their volume leading to a consequent increase of fat mass. Hypertrophy of adipose cells is associated with cellular abnormalities and a massive infiltration of macrophages which induce a state of chronic low-grade inflammation that leads over time to insulin-resistance and eventually type 2 diabetes. Another feature of obesity is remodeling of the extracellular matrix with an excessive accumulation of fibrosis that increases the total stiffness of the obese adipose tissue and reduces expandability of the tissue. Some aspects regarding the development and the progression of fibrosis in adipose tissues in humans remain to be elucidated. In this regard, we performed a systematic study of visceral and subcutaneous fat biopsies from 33 obese patients undergoing bariatric surgery, compared with fat biopsies from 6 lean control patients. We detect that a large percentage of omental and subcutaneous adipocytes are PLIN1-negative, and a positive correlation between the amount of PLIN1-negative adipose cells is found in both adipose depots considered. The amount of non-viable adipose cells is significantly correlated with total fibrosis in all obese patients, in fact PLIN1-negative adipocytes, single or grouped, are surrounded by fibrotic bundles. Pyroptosis, the main mechanism of cell death of murin hypertrophic adipocytes, is not revealed within fibrotic regions. Furthermore, TEM analyses demonstrate that dense collagen fibrils are closely associated to the external surface of basal membrane of adipocytes, more in obese than lean subjects, consistent with hyperproduction of collagen fibrils by adipocytes themselves, and signs of cellular stress in degenerating adipocytes were also found. Finally, data support the idea that a large proportion of hypertrophic adipose cells die, due to hyperproduction of collagen fibrils and they consequently recruit inflammatory cells to clean up the adipose tissue. Macrophages are prevalent mainly in the parenchyma and only to a lesser extent in Crown-like Structures (CLS), unlike the mouse models. They probably induce insulin-resistance, and this could explain the pathogenetic hypothesis of the link between obesity and diabetes. Therefore, in humans we hypothesize that, in addition to death of pyroptosis, there could be another type of cell death for obese adipocytes, related to fibrosis. The clinical significance of this new aspect of the histopathology of adipose tissue in obese people remains to be indagated.File | Dimensione | Formato | |
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