Body fat distribution is a strong determinant of human metabolic health but the mechanisms underpinning regional deposition of white adipose tissue (WAT) remain poorly understood. WAT also exhibits striking depot-specific functional properties. The aim of this project was to investigate the potential role of specific candidate genes implicated in regulating WAT development and/or function in a depot-specific manner. Cartilage oligomeric matrix protein (COMP) is an extracellular matrix protein that is highly differentially expressed between subcutaneous abdominal and gluteal WAT but has primarily been studied in the context of bone biology. WAT COMP expression was found to be significantly up-regulated in obesity; COMP expression in preadipocytes was increased by glucocorticoids; and COMP promoted adipogenesis in (immortalised) subcutaneous abdominal and gluteal preadipocytes. Building on a finding during the COMP study, bone morphogenetic protein (BMP)-2 was identified as another candidate. BMP2 exerts positive adipogenic effects in murine models and a recent genome-wide association study meta-analysis identified a significant association between BMP2 and body fat distribution. BMP2 was found to exert a pro-adipogenic effect specifically in subcutaneous abdominal preadipocytes, with this effect requiring activation of SMAD1/5/8 signalling via type 1 BMP receptors. These data identify BMP2 as a novel depot-specific regulator of human adipogenesis. Particularly lipid-laden cells were formed when conventional adipogenic medium was supplemented with fatty acids; these cells were captured, de-differentiated (DFAT) and expanded to generate immortalised abdominal and gluteal DFAT cells. These DFAT cells exhibit a greatly enhanced adipogenic potential compared to the mixed stromovascular (SVF) population from which they derive and retained an intrinsic memory of their anatomical origin. The use of DFAT cells is likely to represent a valid and enhanced model system to study various depot-specific aspects of WAT biology such as adipogenesis. Overall, the data from this thesis emphasise the striking depot-specific biology exhibited by WAT and provide novel insights into the mechanisms governing the regional distribution of WAT in humans.

Made available in DSpace on 2014-06-11T19:27:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-11-22Bitstream added on 2014-06-13T18:31:48Z : No. of bitstreams: 1 santos_tab_me_botfmvz.pdf: 146691 bytes, checksum: 6aae72e35b656f301db29d0db1532c3a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / Com o objetivo de avaliar a composição do ganho e as curvas de crescimento de componentes corporais, foram utilizados 32 bubalinos da raça Mediterrâneo, recriados em pastagem nativa do litoral norte de São Paulo, não castrados, com idade média de 14 meses e peso vivo médio inicial de 330 Kg. Os animais foram divididos aleatoriamente em 5 grupos experimentais (grupo I, grupo II, grupo III e grupo IV), de sete animais em cada grupo e um grupo referência de 4 animais (grupo AB). Foi fornecida a mesma dieta ad libitum a todos os animais, duas vezes por dia. O abate foi precedido de jejum de sólidos de 16 horas, permanecendo livre acesso à água. O grupo controle (grupo AB) foi abatido logo após o período de adaptação de 30 dias e os demais grupos foram pesados a cada 28 dias até atingirem o peso pré estabelecido para o abate de 450 (grupo I), 480 (grupo II), 510 (grupo III) e 540 kg (grupoIV). Após o abate, as carcaças foram resfriadas por 18 horas a -5oC e a 9o, 10o e 11o costelas da meia carcaça esquerda foram submetidas à secção HH para verificar a proporção de ossos, músculo e gordura na carcaça. Para predição dos conteúdos de músculo, tecido adiposo e ossos da carcaça dos animais no corpo vazio, adotou-se a equação de regressão do logaritmo do conteúdo destes componentes no corpo vazio, em função do logaritmo do peso do corpo vazio – PCVZ (ARC, 1980). Derivando-se as equações acima, obtiveram-se as equações de predição da participação dos componentes corporais no ganho de 1 kg de peso de corpo vazio (GPCVZ). Na carcaça, o tecido adiposo teve maior impulso de crescimento em idade mais tardia, os tecidos ósseo e muscular tiveram maior impulso para crescimento em idade mais precoce. A carcaça apresentou alometria com valores bem próximos a 1, refletindo o seu desenvolvimento foi proporcionalmente igual ao desenvolvimento do PCVZ. / The present study was performed to evaluate the relative growth of tissues in carcass of young buffaloes. Thirty and two Mediterranean non-castrated buffalo males, with an average age of 14 months and an initial living Weight of approximately 330 kilos, raised on native pasture on north litoral of Sao Paulo State, were randomly distributed in five experimental groups (I, II, III, IV) with 7 animals each and another four animals were considered as control group (AB). All of them received the same experimental diet ad libitum, twice daily. Animals were kept under solid fasting 16 hours before slaughter with free access to water. The experiment did not have a pre-defined duration, control group (AB) was slaughtered after an adaptation period of 30 days and the other groups were weighted every 28 days until they reached the pre-established weights of 450 (group I), 480 (group II), 510 (group III) and 540 kg (group IV). They were weighted every 28 days and as an animal approached the expected weight the measurement was performed in smaller intervals. After slaughter, each carcass was divided into two halves using a chainsaw, were individually weighted and then chilled for approximately 18 hours under - 5oC. Then the left half was submitted to a transversal section that included the 9a, 10a and 11a ribs in which the HH section was performed to a further and proportional analysis of muscle, adipose and bone tissues. The following regression formula of the logarithm of carcass and tissues (muscle, adipose and bone) Weights in function of the logarithm of empty body Weight. In the carcass, adipose tissue presented a late growth while bone and muscular tissues developed in an earlier age. The carcass presented alometric coeficient with approach value 1, reflecting its development was proportionally the same to the development of the PCVZ.

Orientador: André Mendes Jorge / Banca: Renata Bonini Pardo / Banca: Heraldo César Gonçalves / Resumo: Com o objetivo de avaliar a composição do ganho e as curvas de crescimento de componentes corporais, foram utilizados 32 bubalinos da raça Mediterrâneo, recriados em pastagem nativa do litoral norte de São Paulo, não castrados, com idade média de 14 meses e peso vivo médio inicial de 330 Kg. Os animais foram divididos aleatoriamente em 5 grupos experimentais (grupo I, grupo II, grupo III e grupo IV), de sete animais em cada grupo e um grupo referência de 4 animais (grupo AB). Foi fornecida a mesma dieta ad libitum a todos os animais, duas vezes por dia. O abate foi precedido de jejum de sólidos de 16 horas, permanecendo livre acesso à água. O grupo controle (grupo AB) foi abatido logo após o período de adaptação de 30 dias e os demais grupos foram pesados a cada 28 dias até atingirem o peso pré estabelecido para o abate de 450 (grupo I), 480 (grupo II), 510 (grupo III) e 540 kg (grupoIV). Após o abate, as carcaças foram resfriadas por 18 horas a -5oC e a 9o, 10o e 11o costelas da meia carcaça esquerda foram submetidas à secção HH para verificar a proporção de ossos, músculo e gordura na carcaça. Para predição dos conteúdos de músculo, tecido adiposo e ossos da carcaça dos animais no corpo vazio, adotou-se a equação de regressão do logaritmo do conteúdo destes componentes no corpo vazio, em função do logaritmo do peso do corpo vazio - PCVZ (ARC, 1980). Derivando-se as equações acima, obtiveram-se as equações de predição da participação dos componentes corporais no ganho de 1 kg de peso de corpo vazio (GPCVZ). Na carcaça, o tecido adiposo teve maior impulso de crescimento em idade mais tardia, os tecidos ósseo e muscular tiveram maior impulso para crescimento em idade mais precoce. A carcaça apresentou alometria com valores bem próximos a 1, refletindo o seu desenvolvimento foi proporcionalmente igual ao desenvolvimento do PCVZ. / Abstract: The present study was performed to evaluate the relative growth of tissues in carcass of young buffaloes. Thirty and two Mediterranean non-castrated buffalo males, with an average age of 14 months and an initial living Weight of approximately 330 kilos, raised on native pasture on north litoral of Sao Paulo State, were randomly distributed in five experimental groups (I, II, III, IV) with 7 animals each and another four animals were considered as control group (AB). All of them received the same experimental diet ad libitum, twice daily. Animals were kept under solid fasting 16 hours before slaughter with free access to water. The experiment did not have a pre-defined duration, control group (AB) was slaughtered after an adaptation period of 30 days and the other groups were weighted every 28 days until they reached the pre-established weights of 450 (group I), 480 (group II), 510 (group III) and 540 kg (group IV). They were weighted every 28 days and as an animal approached the expected weight the measurement was performed in smaller intervals. After slaughter, each carcass was divided into two halves using a chainsaw, were individually weighted and then chilled for approximately 18 hours under - 5oC. Then the left half was submitted to a transversal section that included the 9a, 10a and 11a ribs in which the HH section was performed to a further and proportional analysis of muscle, adipose and bone tissues. The following regression formula of the logarithm of carcass and tissues (muscle, adipose and bone) Weights in function of the logarithm of empty body Weight. In the carcass, adipose tissue presented a late growth while bone and muscular tissues developed in an earlier age. The carcass presented alometric coeficient with approach value 1, reflecting its development was proportionally the same to the development of the PCVZ. / Mestre

Thesis (Ph. D.)--Ohio State University, 2007. / Includes bibliographical references (p. 139-160).