yes / Inflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling. AMPK activation inhibited TNF-α-stimulated IKK/IκB/NFκB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKα1−/− mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue. / British Heart Foundation

No / Adiponectin reportedly stimulates proliferation and elongation of human scalp hair follicles (HFs) ex vivo. In the current study, we investigated how adiponectin oligomers produced by perifollicular dermal white adipose tissue (dWAT), a potent source of adiponectin isoforms, influence human HF proliferation and pigmentation. To do so, we treated microdissected, organ-cultured HFs in the presence or absence of dWAT with a recombinant human adiponectin oligomer mix, or inhibited dWAT-derived adiponectin using a neutralizing antibody. Multiplex qPCR (Fluidigm) revealed that adiponectin oligomers downregulated pigmentation genes KITLG, PMEL and TYRP1 and Wnt genes AXIN2, LEF1 and WNT10B. In situ hybridization showed that adiponectin downregulated AXIN2 and LEF1, and up-regulated DKK1 within the dermal papilla (DP), a highly unusual transcriptional profile for a putative hair growth-promoting agent. Adiponectin oligomers also downregulated protein expression of the HGF receptor c-Met within the matrix and DP. However, adiponectin did not alter hair matrix keratinocyte proliferation within 48 h ex vivo, irrespective of the presence/absence of dWAT; HF pigmentation (Masson-Fontana histochemistry, tyrosinase activity) was also unchanged. In contrast, neutralizing adiponectin isoforms within HF + dWAT increased proliferation, melanin content and tyrosinase activity but resulted in fewer melanocytes and melanocytic dendrites, as assessed by gp100 immunostaining. These seemingly contradictory effects suggest that adiponectin exerts complex effects upon human HF biology, likely in parallel with the pro-pigmentation effects of dWAT- and DP-derived HGF. Our data suggest that dWAT-derived ratios of adiponectin isoforms and the cleaved, globular version of adiponectin may in fact determine how adiponectin impacts upon follicular pigmentation and growth. / Biotechnology and Biological Science Research Council (BBSRC) iCASE Studentship (awardees: R.P., J.P., recipient: C.N.), co-funded by Unilever, Colworth, UK; NIHR Manchester Biomedical Research Centre, Inflammatory Hair Diseases Programme (Lead: R.P.), University of Miami start-up funds (R.P.), and Frost Endowed Scholarship to R.P. (Dept. of Dermatology).

京都大学 / 新制・課程博士 / 博士(農学) / 甲第24914号 / 農博第2577号 / 新制||農||1103(附属図書館) / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 井上 和生, 教授 佐々木 努, 准教授 後藤 剛 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

<p><strong>Introduction: </strong>Obesity is associated with asthma and airway hyperresponsiveness, though the mechanisms behind this relationship remain unclear. It is unlikely to be due to a direct effect of leptin on human airway smooth muscle cells (ASMC) (Nair, <em>et al.</em>, 2009). Since adipocytes are known to produce a wide array of mediators, we hypothesized that adipocytes may directly modulate human ASMC biology.</p> <p><strong>Objectives:</strong> To determine and compare the effects of intra and extrathoracic adipocyte secretions on ASMC proliferation, chemotaxis, contractility and cytokine synthesis.</p> <p><strong>Methods:</strong> Human ASMC and human adipocytes were cultured from primary samples (intrathoracic or extrathoracic). Adipocyte-conditioned media was used as a treatment in proliferation cell count assays, Transwell migrations, muscle bath experiments and to induce interleukin (IL)-6, tumor necrosis factor (TNF)-α and eotaxin production (as measured with a Bioplex). The effects of adipocyte-myocyte co-culture were also investigated on the proliferation, migration and cytokine synthesis of the ASMC.</p> <p><strong>Results: </strong>Adipocyte supernatants and co-culture did not significantly affect the growth of ASMC in the presence of 10% fetal calf serum. The adipocyte supernatants were not chemotactic, and did not affect the migration of ASMC towards platelet derived growth factor (PDGF). Similarly, co-culture did not have any effect on ASMC chemotaxis. Cytokine synthesis was also unchanged by adipocytes. Adipocyte supernatants did not have any effect on the contractile or relaxant responses of bovine tracheal smooth muscle strips. There was no significant difference between adipocyte depot location, with intrathoracic and extrathoracic adipocytes having a similar effect.</p> <p><strong>Conclusion:</strong> Human adipocytes do not directly modulate airway smooth muscle proliferation, migration, contractility and cytokine synthesis. These data point to some other cause for the association between obesity and asthma, though the role of other cells present in the adipose tissue of obese individuals cannot be ruled out.</p> / Master of Science (MSc)

Introduction : Ce programme de recherche visait à étudier l'impact d'une intervention de 8 mois entrainant une perte de poids induite par l'activité physique et la nutrition sur la santé osseuse chez des adolescents obèses. L'objectif global de cette thèse était d'examiner l'impact d'une intervention de perte de poids sur les paramètres osseux chez les adolescents obèses.Méthode : Soixante-cinq adolescents ont été recrutés : 31 (6 garçons) obèses pour le groupe intervention (âge : 13,61 (1,27)), 23 adolescents de poids normal (NW) (âge : 15,90 (0,43)) et 11 (4 hommes) adolescents obèses pour le groupe témoin (14.02 (1.39)). Le critère d’évaluation principal concernait la densitométrie osseuse par DXA (corps entier, colonne vertébrale, hanche). Les critères d'évaluation secondaires comprenaient la composition corporelle (DXA), la géométrie et la résistance des os (analyse structurelle de la hanche) et des biomarqueurs osseux (propeptide N-terminal (P1NP) procollagène de type 1, estradiol C-télopeptide (CTx), leptine). Les données ont été collectées au départ à 4 mois et à 8 mois. Les données ont été ajustées en fonction des changements de poids corporel, de masse grasse et de masse maigre.Résultats : Comparés au groupe contrôle de poids normal, les adolescents obèses présentaient une densité osseuse non ajustée et ajustée inférieure. Suite à la perte de poids (~ -11%), les adolescents obèses ont augmentés leur densité osseuse au corps entier (% Ob 3,22 (3,58) p <0,001) et à la colonne lombaire (% Ob 6,27 (12,45) p = 0,014). Cependant, ces valeurs restent inférieures à celles de leurs homologues contrôle de poids normal après ajustement aux variations de poids corporel. Après l’intervention entrainant une perte de poids, les estimations du risque de fracture sont restées élevée, en particulier au niveau du col étroit (buckling ratio (BR) 8,25 (2,00) p = 0,005) et ce malgré des adaptations positives de certaines propriétés géométriques (i.e. NN CSA, NN Z). De plus, les modifications de l'accrétion osseuse chez les adolescents obèses suivent une adaptation de type androgènes, cela est démontrée par une expansion périostée (% NW ∆ 0,69 (3,71); Ob ∆ 1,67 (9,11)) et une résorption endocorticale (% NW ∆ -2,11 (11,79); Ob ∆ 4,42 (10,56)). Dans le groupe intervention, les différences au regard des marqueurs osseux favorisent la formation osseuse au cours des 4 premiers mois alors que par la suite la résorption osseuse est favorisée.Conclusion : La fragilité osseuse chez les adolescents obèses a été démontrée par (1) une densité minérale osseuse inférieure corps entier et régionale pré et post-intervention par rapport aux contrôles normo-pondérés, (2) un indice de risque de fracture élevé après intervention au niveau du cou étroit, (3) des biomarqueurs osseux démontrant des z-scores, indices de découplage (uncoupling indices) et représentations qualitatives de la distribution du remodelage osseux inférieures. Les résultats de cette thèse contribuent aux recherches futures sur les liens entre os et obésité à l’adolescence. / Introduction: This program of research targeted the impact of an 8-month weight loss intervention induced by physical activity and nutrition on bone health in adolescents with obesity. The overall aim of this thesis was to examine the impact of a lifestyle weight loss intervention on the bone parameters in adolescents with obesity. Method: Sixty-five adolescents were recruited: 31 (6 males) adolescents with obesity in the weight loss intervention (age: 13.61 (1.27)), 23 normal weight (NW) adolescents (age: 15.90 (0.43)) and 11 (4 males) adolescents with obesity in another control group (14.02 (1.39)). Primary outcomes targeted bone densitometry (whole body, spine, hip DXA). Secondary outcomes included body composition, bone geometry and strength (hip structural analysis) and bone biomarkers (procollagen type 1 N-terminal propeptide (P1NP), C telopeptide (CTx) estradiol, leptin). Data were collected at baseline, 4 months and 8 months. Data were adjusted for body weight, fat mass and lean mass changes.Results: Compared with the NW controls, adolescents with obesity displayed lower unadjusted and adjusted bone density. Following successful weight loss (~ -11%) adolescents with obesity increased whole body (%Ob ∆ 3.22 (3.58) p<0.001) and lumbar spine (%Ob ∆ 6.27 (12.45) p=0.014) BMD. However, values remain lower than their NW peers after adjustment to body weight changes. After the weight loss intervention, compromised estimates of fracture risk remained especially at the narrow neck (buckling ratio (BR) 8.25 (2.00) p=0.005), despite positive adaptations of some geometric properties (i.e. NN CSA, NN Z). Also, bone accretion changes in adolescents with obesity followed an androgen-like adaptation demonstrated by periosteal expansion (% NW ∆ 0.69 (3.71); Ob ∆ 1.67 (9.11)) and endocortical resorption (% NW ∆ -2.11 (11.79); Ob ∆ 4.42 (10.56)). Among the intervention group, differences in bone markers favoured formation during the first 4 months and favoured resorption in the remaining months.Conclusion: Bone fragility in adolescents with obesity was demonstrated by (1) baseline and post intervention lower whole body and regional BMD than NW controls, (2) post-intervention higher fracture risk index at the narrow neck, (3) bone biomarkers showing reduced z-scores, uncoupling indices and qualitative representations of the distribution of bone remodeling. Future investigations of links between bone and obesity during adolescence can be well informed by the results of this thesis.

Le vieillissement est associé un mécanisme d'arrêt du cycle cellulaire nommé senescence. Au niveau de l'adipocyte, cet état cellulaire semble contribuer à la survenue d'altérations métaboliques et à un état pro-inflammatoire. Dans ce contexte, le tissu adipeux blanc viscéral pourrait jouer un rôle déterminant sur la perte du contrôle métabolique et ainsi participer à l'installation de pathologies associées au vieillissement. Au cours du vieillissement, le tissu adipeux blanc subit des modifications morphologiques et physiologiques conduisant à une altération progressive des fonctions de stockage et endocrines de l'adipocyte. Ainsi, un nouveau profil sécrétoire pro-inflammatoire appelé SASP (Senescence Associated Secretory Phenotype) a pu être mis en évidence et pourrait être impliqué dans la survenue de différentes pathologies liées à l'âge (diabète, insuffisance cardiaque ou rénales, ...). Dans ce sens, l'analyse précise du SASP d'adipocytes issus de souris de différents âges nous a permis d'identifier une cytokine pro-inflammatoire, l'haptoglobine, comme un nouveau candidat potentiellement impliqué dans les désordres métaboliques et inflammatoires associés au vieillissement. Nos premiers résultats montrent que, via une boucle de régulation, la senescence augmente la production d'haptoglobine adipocytaire et que réciproquement., cette production entretien la senescence de l'adipocyte Au niveau fonctionnel, l'haptoglobine altère les principales fonctions adipocytaires métaboliques telles que la lipolyse et la sensibilité à l'insuline. Des expériences sont en cours afin de confirmer in vivo l'importance de cette adipocytokine sur les altérations métaboliques entrainant une accélération du vieillissement de l'organisme. Cette étude permettra de mieux comprendre la participation de l'haptoglobine dans la perte des fonctions du tissu adipeux afin de développer de nouvelles stratégies thérapeutiques pour ralentir les processus de vieillissement. / Aging is associated with a cell cycle arrest mechanism named senescence. In adipocyte, this cell state could contribute to metabolic alterations as well as a low-grade inflammatory state. In this context, visceral white adipose tissue could play a major role in age-associated setup pathologies through the loss of metabolic control. Indeed, during aging, white adipose tissue undergoes functional and morphological modifications progressively leading to altered storage and endocrine capacities. Consequently, it has been hypothesized that a new emerging adipocyte secretory profile associated with aging (SASP for senescence associated secretory phenotype) could actively participate to the progressive onset of metabolic diseases related to aging. By proteomic analysis, we identified haptoglobin as a new proinflammatory cytokine overproduced by murine adipose tissue during aging. Our results showed a regulatory feedback loop between adipocyte haptoglobin and senescence state arguing for a role of the cytokine in aging process. Moreover, haptoglobin induced adipocyte metabolic alterations in vitro targeting lipolysis and insulin sensitivity. In vivo validation of haptoglobin's role on metabolic-induced aging are currently ongoing. Our study will allow a better understanding of haptoglobin's role in age-related adipose tissue loss of function and will pave the road for a new therapeutic strategy in the field of metabolism and age-associated pathologies.

La progression tumorale dépend d'un dialogue entre les cellules cancéreuses et leur environnement. Parmi les cellules du microenvironnement du mélanome, les adipocytes ont longtemps été ignorés. Pourtant, ces cellules sont le composant majeur de l'hypoderme, la couche la plus profonde de la peau. Ainsi, elles sont proches du mélanome lors de la tumorigenèse et, lorsque la tumeur envahi les couches profondes de la peau, les deux types cellulaires entrent en contact. Il est donc important de comprendre l'impact des adipocytes sur la progression du mélanome, d'autant plus que des études épidémiologiques montrent que l'obésité est un facteur de mauvais pronostic pour ce cancer. Le surpoids et l'obésité sont en hausse constante avec près d'un tiers de la population mondiale affectée, faisant du lien entre l'obésité et le cancer un enjeu de santé publique majeur. Parmi les différents moyens de communication cellulaire, les vésicules extracellulaires (VE) jouent un rôle important dans le cancer. Les VE régulent la communication entre les cellules cancéreuses mais aussi entre les composants du microenvironnement et la tumeur. Les VE sécrétées par les adipocytes sont peu caractérisées et leur rôle sur la progression tumorale reste à élucider. Les VE adipocytaires pourraient être modifiées qualitativement et quantitativement en obésité car différents stress (inflammation, hypoxie...), connus pour modifier les VE, sont retrouvées dans le tissu adipeux d'individus obèses. Dans ce contexte, le premier objectif de ma thèse était de caractériser les VE adipocytaires et déterminer leur impact sur le mélanome dans un contexte normopondéral et d'obésité. Les résultats obtenus montrent que ces VE favorisent la migration et l'invasion des cellules de mélanome. Une analyse protéomique a révélé une signature spécifique dans ces VE, fortement enrichies en protéines du métabolisme des acides gras (AG).[...] / It is now clear that tumor progression is the result of a permanent dialog between cancer cells and the tumor microenvironment (TME). Among the cells found within the melanoma microenvironment, adipocytes had long been ignored. However, adipocytes are the main component of the hypodermis, the deepest skin layer, and are therefore close to melanoma from tumorigenesis and, as the tumor becomes aggressive and invades the deeper skin layers, the two cell types come into contact. Thus, understanding how adipocytes influence melanoma progression is of major importance, especially since epidemiological studies show that obesity is a poor prognosis factor for melanoma. As overweight and obesity are constantly rising and affect around a third of the World's population, the link between obesity and cancer is a major public health issue. Among the different ways in which cells communicate, extracellular vesicles (EV) play a particularly important role in cancer. Moreover, not only can tumor cells communicate with each other through EV, but the cellular components of the TME also use EV to communicate with cancer cells. Adipocyte-derived EV are poorly characterized and their role in tumor progression remains to be determined. In obesity, adipocyte EV may be qualitatively and quantitatively altered since various stresses (inflammation, hypoxia etc.), which are known to modify EV, are found in the adipose tissue of obese individuals. In this context, the first aim of my thesis was to characterize adipocyte EV and their impact on melanoma in lean and obese individuals. The results obtained show that EV secreted by adipocytes promote migration and invasion of melanoma cells. Analysis of their proteome revealed a protein signature specific to adipocyte EV, which was highly associated with fatty acid (FA) metabolism, a metabolic pathway involved in tumor aggressiveness. In melanoma treated with adipocyte EV, fatty acid oxidation (FAO) is increased and FAO inhibitors reverse their pro-invasive effect. Moreover, adipocytes secrete increased numbers of EV in obesity and, using equal numbers of EV from lean or obese subjects, their effect on tumor aggressiveness is increased and remains dependent on FAO. T[...]

Introdução: Ao ser usado o retalho de omento dissecado por videolaparoscopia no tratamento de deformidades da mama, foi constatado um significativo aumento do seu volume nos primeiros meses após a sua transposição, em todas as pacientes operadas, o que não é visto com essa magnitude em nenhum outro retalho adiposo. Métodos: Para se estudar o motivo desse aumento de volume, foram realizados estudos histológicos de amostras de omento coletadas no primeiro tempo cirúrgico, logo após sua transposição da cavidade abdominal para a região mamária e, no segundo tempo cirúrgico, durante a complementação de tratamento para a simetrização das mamas de oito pacientes. Foram documentadas as modificações nas medidas morfométricas dos adipócitos (perímetro, diâmetro e área), na densidade microvascular mediante o marcador endotelial CD31 e na expressão imunohistoquímica do fator de crescimento do endotélio vascular (VEGF). Resultados: O aumento do tamanho dos adipócitos e da densidade microvascular foi estatisticamente significativo (P≤0,012). O valor do VEGF foi menor na segunda amostra em relação com a primeira, redução esta que não atingiu significância considerável (P<0,093). Conclusão: Estes resultados sinalizam um aumento no volume celular que se mostrou consistente quando foram utilizados três diferentes processos de medida: perímetro, diâmetro e área dos adipócitos. Além disso, o aumento do número de vasos na segunda amostra sugere que tenha ocorrido neoangiogênese estimulada pelo aumento inicial dos valores do VEGF. Portanto o aumento do volume do retalho se deve a neovascularização e hipertrofia do adipócito. / Introduction: When laparoscopically harvested omentum flap was used to treat breast deformities, a significant volume increase, which had never been noticed in any other adipose flap, was observed in all the patients in the first months following its transposition. Methods: Histological studies of omentum samples were performed to study the reason for this increase. Samples were harvested at the first surgical time, right after the transposition of the omentum from the abdominal cavity to the breast region, and at the second surgical time, during treatment complementation for breast symmetrization of eight patients submitted to the transposition of the omentum flap. Modifications in the morphometric measurements of the adipocytes (perimeter, diameter, and area), in the microvascular density by the CD31 endothelial marker and in the imunohistochemic expression of VEGF were documented. Results: the increase in adipocyte size and microvascular density was statistically significant (P≤0.012). The value of VEGF was lower in the second sample, which was not significant (P<0.093). Conclusion: These results suggest an increase in cellular volume that was consistent when three different measurement procedures were used: adipocyte perimeter, diameter, and area. Moreover, the increase in the number of vessels in the second sample suggests neoangiogenesis stimulated by the initial increase in VEGF values obtained in the first sample. The flap increase was probably caused by adipocyte hypertrophy, resulting from the neoangiogenesis.

Les récepteurs couplés aux protéines G (RCPG) constituent la plus grande famille de récepteurs membranaires. Ils contrôlent de nombreux processus physiologiques et leurs implications dans de nombreuses pathologies fait de cette famille une cible de près de 30% des médicaments. Cependant nombre d'entre eux sont orphelins et/ou possèdent des fonctions inconnues, constituant ainsi un réservoir important de cibles pharmacologiques.Afin de déterminer quelles peuvent être les applications thérapeutiques des RCPG, il faut être capable d'identifier les tissus dans lesquels ils s'expriment et ont des effets biologiques. Pour cela, nous avons développé une approche de PCR quantitative à haut débit permettant l'étude de l'ensemble des gènes codants les RCPG murin.Nous avons tout d'abord recherché tous les endoRCPG de souris et pour chacune des séquences identifiées un couple d'amorces a été synthétisé.Nous avons ensuite utilisé cette banque d'amorces dans deux modèles de différenciation cellulaire. La culture primaire de neurones granulaires du cervelet et une lignée de préadipocytes.Nous nous sommes appuyés sur l'hypothèse suivante : si l'expression d'un RCPG varie au cours d'un phénomène particulier, c'est qu'il est possiblement impliqué dans la régulation de celui-ci.Nous avons donc dans un premier temps identifié les endoRCPG dont l'expression variait au cours de la différenciation cellulaire. Dans un deuxième temps nous avons testé par des approches pharmacologiques et de biologie cellulaire l'implication de ces récepteurs dans la régulation des divers aspects de la différenciation cellulaire des modèles étudiés. / G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and control numerous physiological processes. Accordingly, ~45% of drugs used to treat human pathologies target a GPCR. However, a number of GPCRs are orphans and/or involved in unknown functions, which makes GPCRs an attractive reservoir of pharmacological targets.To identify novel therapeutic applications of GPCR ligands, it is necessary to identify organs in which GPCRs are expressed and have biological effects. To that end, we developed a high-throughput, real-time PCR approach to quantify each and every murine GPCR transcripts. We first established a census of all endo-GPCRs, i.e. those GPCRs having an endogenous ligand, encoded in the murine genome. We then designed and validated a primer pair for each identified sequence.We used this primer collection in 2 models of cell differentiation, namely primary cultures of cerebellar granule neuroblasts and the preadipocyte 3T3-L1 cell line. Our basic premise in this approach is that changes in the expression levels of a GPCR in a given biological phenomenon is an indication that this GPCR might be functionally relevant to the biological process under study.We first focused on GPCRs whose expression changed during cellular differentiation, which enabled the identification of candidate GPCRs in this phenomenon. Using pharmacological and genomic tools, we tested the implication of those candidates in various aspects of cell differentiation. In particular, we performed a detailed study of the role of the F2r thrombin receptor and Gprc5a orphan receptor in preadipocyte proliferation.

Introdução: Ao ser usado o retalho de omento dissecado por videolaparoscopia no tratamento de deformidades da mama, foi constatado um significativo aumento do seu volume nos primeiros meses após a sua transposição, em todas as pacientes operadas, o que não é visto com essa magnitude em nenhum outro retalho adiposo. Métodos: Para se estudar o motivo desse aumento de volume, foram realizados estudos histológicos de amostras de omento coletadas no primeiro tempo cirúrgico, logo após sua transposição da cavidade abdominal para a região mamária e, no segundo tempo cirúrgico, durante a complementação de tratamento para a simetrização das mamas de oito pacientes. Foram documentadas as modificações nas medidas morfométricas dos adipócitos (perímetro, diâmetro e área), na densidade microvascular mediante o marcador endotelial CD31 e na expressão imunohistoquímica do fator de crescimento do endotélio vascular (VEGF). Resultados: O aumento do tamanho dos adipócitos e da densidade microvascular foi estatisticamente significativo (P≤0,012). O valor do VEGF foi menor na segunda amostra em relação com a primeira, redução esta que não atingiu significância considerável (P<0,093). Conclusão: Estes resultados sinalizam um aumento no volume celular que se mostrou consistente quando foram utilizados três diferentes processos de medida: perímetro, diâmetro e área dos adipócitos. Além disso, o aumento do número de vasos na segunda amostra sugere que tenha ocorrido neoangiogênese estimulada pelo aumento inicial dos valores do VEGF. Portanto o aumento do volume do retalho se deve a neovascularização e hipertrofia do adipócito. / Introduction: When laparoscopically harvested omentum flap was used to treat breast deformities, a significant volume increase, which had never been noticed in any other adipose flap, was observed in all the patients in the first months following its transposition. Methods: Histological studies of omentum samples were performed to study the reason for this increase. Samples were harvested at the first surgical time, right after the transposition of the omentum from the abdominal cavity to the breast region, and at the second surgical time, during treatment complementation for breast symmetrization of eight patients submitted to the transposition of the omentum flap. Modifications in the morphometric measurements of the adipocytes (perimeter, diameter, and area), in the microvascular density by the CD31 endothelial marker and in the imunohistochemic expression of VEGF were documented. Results: the increase in adipocyte size and microvascular density was statistically significant (P≤0.012). The value of VEGF was lower in the second sample, which was not significant (P<0.093). Conclusion: These results suggest an increase in cellular volume that was consistent when three different measurement procedures were used: adipocyte perimeter, diameter, and area. Moreover, the increase in the number of vessels in the second sample suggests neoangiogenesis stimulated by the initial increase in VEGF values obtained in the first sample. The flap increase was probably caused by adipocyte hypertrophy, resulting from the neoangiogenesis.