No description available.

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2009 / Epidemiological trends suggest that obesity is becoming a major public health problem. Although obesity contributes toward cardiovascular risk by promoting the development of hypertension, dyslipidaemia and diabetes mellitus (conventional risk factors), there is increasing evidence to suggest that excess adiposity may increase risk through effects on cardiovascular target organs that are independent of conventional risk factors. These obesity-induced effects may be produced by mediating damage and dysfunction of large vessels and the heart, and by promoting the development of cardiac hypertrophy. However, the independent effect of excess adiposity on large vessels has not been confirmed in all studies. Moreover, whether the impact of excess adiposity on cardiac hypertrophy or cardiac damage and dysfunction is dependent on an interaction with blood pressure (BP) is uncertain. In the present thesis I addressed these questions. Before evaluating these questions I first identified the preferred clinical index of adiposity when predicting BP. In this regard, some, but not all studies support the notion that indexes of central adiposity (waist circumference or waist-to-hip ratio) are the preferred predictors of conventional BP over indexes of general (body mass index) or subcutaneous (skin-fold thickness) adiposity. Moreover, to my knowledge no study has been conducted in a large study sample to evaluate whether indexes of central adiposity are the preferred predictors of ambulatory BP, a measure of BP that is more closely associated with cardiovascular events than conventional BP. In the first study conducted in a relatively large, randomly selected population sample (n=300) with a high prevalence of excess adiposity (65%), I demonstrated that waist circumference is the only clinical index of adiposity that is associated with an increased conventional and ambulatory systolic and diastolic BP, independent of other indexes of adiposity. With regards to the effects of excess adiposity on large arteries, there is inconsistency in the reports demonstrating relations between indexes of adiposity and large artery dysfunction (arterial stiffness) independent of factors such as BP, heart rate and diabetes mellitus. As convincing independent relations between clinical indexes of adiposity and arterial stiffness have been noted in older, but not in younger populations, I hypothesized that age may determine whether excess adiposity promotes increases in arterial stiffness independent of confounders. Indeed, in 508 randomly selected persons from a population sample with a high prevalence of excess adiposity (~63% overweight or obese), I was able to show that age markedly influenced the independent relationship between indexes of central adiposity and an index of large artery stiffness in women but not in men after adjusting for confounders. The adjusted effect of indexes of central obesity on arterial stiffness was ~5-fold higher in older than in younger women. With respect to the impact of excess adiposity on cardiac growth, although severe obesity is associated with an enhanced impact of BP on left ventricular mass (LVM), there is uncertainty as to whether the same effects occur in milder forms of excess adiposity, data confounded by the high prevalence of participants receiving antihypertensive therapy in previous studies. In the present thesis I demonstrated in a randomly recruited population sample of 398 participants with a high prevalence of mild-to-moderate obesity and hypertension (~41%), but in whom antihypertensive use was limited (~17%), that adiposity is indeed associated with an enhanced impact of conventional and ambulatory BP or arterial stiffness on LVM index and wall thickness independent of additional conventional risk factors. With regards to the impact of obesity on cardiac function, although obesity is a risk factor for heart failure independent of other conventional cardiovascular risk factors, whether this effect occurs through changes in cardiac systolic chamber function is uncertain. In the present thesis I provide the first evidence to show in an animal model of genetic iv hypertension and dietary-induced obesity, that dietary-induced obesity promotes the progression from compensated cardiac hypertrophy to cardiac pump dysfunction without promoting hyperglycaemia. This effect was attributed to alterations in both intrinsic myocardial systolic dysfunction and cardiac dilatation, effects that were associated with excessive cardiomyocyte apoptosis and activation of enzymes that promote myocardial collagen degradation. Therefore in the present thesis I provide evidence to support the notion that waist circumference should hypertension and dietary-induced obesity, that dietary-induced obesity promotes the progression from compensated cardiac hypertrophy to cardiac pump dysfunction without promoting hyperglycaemia. This effect was attributed to alterations in both intrinsic myocardial systolic dysfunction and cardiac dilatation, effects that were associated with excessive cardiomyocyte apoptosis and activation of enzymes that promote myocardial collagen degradation. Therefore in the present thesis I provide evidence to support the notion that waist circumference should be measured when predicting BP changes, that excess adiposity does indeed decrease large vessel function independent of conventional risk factors, but that this effect is age-dependent, and that the deleterious effects of excess adiposity on cardiac hypertrophy and cardiac pump function are indeed dependent on an interaction with BP, but not other confounders.

The problem of childhood obesity in South Africa has reached epidemic proportions. It is estimated that one in five South African children are either overweight or obese; with twenty percent of children under the age of six being overweight. This is mainly due to a poor diet and a lack of exercise. The aim of this study is to determine the overweight / obesity prevalence amongst grade-one learners at selected schools in the West Rand, Mogale City. The weight and height of each subject was to be physically measured by the researcher and compared to norms for that age category. This study further aims to determine their parents knowledge / perceptions regarding childhood nutrition and physical activity. To this end a questionnaire was constructed so that parental knowledge / beliefs could be assessed. This study has found both overweight and underweight within the same population. The results indicate overweight / obesity in seventeen subjects (3.7%). Eleven girls (4.8%) and six boys (3%) were overweight representing a boy to girl ratio of 1: 1.8 among the overweight group. Among the overweight subjects, girls represented 65% while boys represented 35%. This study has also found underweight / stunting of growth among the eight and nine year old subjects as their weight for height fell below the 25th percentile. Further classification of the study sample according to school-fee structure revealed that all subjects with overweight / obesity were found within low-fee schools, representing 4%. One boy and one girl each were found with obesity among the overweight group having a body mass index (BMI) of 23.8 and 24.8 respectively. Therefore obesity was found in 12% among the overweight group and within low-fee structure schools.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand , Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science (Medicine) in Human Genetics,2013 / Obesity and hypertension often occur together and are risk factors for cardio-metabolic disorders. Single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor (LEPR) genes have been shown to be associated with obesity and hypertension, but have not been well explored in African populations. The aims of this study were to determine the heritability estimates of anthropometric and blood pressure (BP) measures and leptin levels; to identify additional informative SNPs in and around the LEP and LEPR genes; and to examine the potential relationships between these SNPs and measures of obesity, hypertension and leptin levels in a black South African cohort. Participants from the African Programme on Genes in Hypertension (APOGH) with various anthropometric and BP measurements were genotyped for LEP and LEPR SNPs using the BeadXpress platform. Heritability estimates were determined using Statistical Analysis for Genetic Epidemiology (S.A.G.E.) software and relationships between LEP or LEPR SNPs and obesity, leptin levels and hypertension were assessed using SAS 9.3 and gPLINK vs2.050, taking into account family relationships, various confounders and correcting for multiple testing. The Bonferroni method was used to correct for multiple testing and P≤0.00076 was considered as statistically significant for SNP association tests. Seven-hundred-and-thirteen individuals were successfully genotyped and there were more women (66%) than men. The prevalence of obesity (42%) and hypertension (46%) were high in the sample. Significant heritability (h2 %, P<0.05) was noted for body weight (38%), body mass index (26%), waist (35%) and hip circumference (42%), waist-to-hip ratio (46%), skinfold thickness (44%), systolic (34%), diastolic (27%) and central systolic (33%) BP; but leptin levels were not significantly heritable (h2 %=15%, P=0.228). LEP rs17151914 (P=0.0002) and LEPR rs6690661 (P=0.0007) were significantly associated with leptin levels and diastolic BP, respectively, in women. The LEP rs17151913T-rs6956510G haplotype was associated with an increase in central systolic BP in women (P=0.012 with Bonferroni correction) whereas the LEPR rs2154381C-rs1171261T haplotype was associated with lower systolic BP in men (P=0.0359 with Bonferroni correction). LEP gene variants were significantly correlated with effects on leptin levels in women and the LEPR gene variants were significantly correlated with effects on diastolic BP also in women. These results indicate that further exploration of the role of genetic variation in the LEP and LEPR genes in obesity and hypertension in individuals of African ancestry is warranted.

No description available.

There is considerable evidence to show that obesity is associated with the development of heart failure independent of traditional risk factors. However, clarity is required on the process involved in the transition from obesity-associated left ventricular hypertrophy (LVH) to LV dysfunction. In the present thesis I evaluated the extent to which central obesity explains variations in LV diastolic function at a community level independent of LV mass (LVM), LV remodelling or haemodynamic factors; whether obesity-related increases in LVM exceeding that predicted by workload (inappropriate LVM [LVMinappr] or alternative haemodynamic factors explains variations in LV ejection fraction (EF) at a community level; whether regression of LVMinappr is more closely associated with improvements in EF than LVM or LVM index (LVMI); and whether obesity-associated insulin resistance may explain decreases in LV diastolic function and variations in LVMinappr. Data were obtained in either 626 or 478 participants whom were representative of a randomly selected community sample and in 168 mild to moderate hypertensives treated for 4 months. In 626 randomly selected participants over 16 years of age from a community sample with a high prevalence of excess adiposity (~24% overweight and ~43% obese) after adjustments for a number of confounders including age, sex, pulse rate, conventional diastolic (or systolic) blood pressure (BP), antihypertensive treatment, LVMI and the presence of diabetes mellitus or an HbA1c>6.1%; waist circumference (p=0.0012) was independently and inversely associated with a reduced early-ro-late transmitral velocity (E/A), with similar findings noted for e’/a’ in a subset of 212 participants with tissue Doppler measurements. Waist circumference-E/A relationships persisted even after adjustments for other adiposity indices including body mass index (BMI) (p<0.05-0.005). No independent relationships between adiposity indices and E/e’ were noted (n=212). In contrast to the effects on diastolic function, waist circumference was not correlated with EF (p=0.83). The independent relationship between waist circumference and E/A was second only to age and similar to BP in the magnitude of the independent effect on E/A. The inclusion of relative wall thickness rather than LVMI in the regression equation produced similar outcomes. The inclusion of carotid-femoral pulse wave velocity (PWV), or 24-hour BP as confounders, failed to modify the relationship between waist circumference and E/A. Thus, waist circumference is second only to age in the impact of the independent association with E/A in a community sample with a high prevalence of excess adiposity. This effect was not accounted for by left ventricular hypertrophy or remodelling, 24-hour BP or arterial stiffness. In 478 randomly selected participants from a community sample, waist circumference, but not BMI was independently associated with the homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR was inversely correlated with E/A (p<0.0001) and in a multivariate model with adjustments for waist circumference, age, sex, conventional diastolic or systolic BP, diabetes mellitus or an HbA1c>6.1%, regular tobacco use, regular alcohol intake, pulse rate, treatment for hypertension and either LVMI or LV relative wall thickness in the model, the relationship betwreen HOMA-IR and E/A persisted (partial r=-0.13 to 0.14, p<0.005). With further adjustments for either 24-hour systolic or diastolic BP (partial r=-0.11, p<0.05, n=351) or for aortic PWV (partial r=-0.11, p<0.02, n=410), the independent relationship between HOMA-IR and E/A also remained. Therefore, the relationship between indices of an excess adiposity and abnormalities in LV diastolic function may be explained in-part by insulin resistance beyond haemodynamic factors. In 626 randomly selected adult participants from a community sample with a high prevalence of obesity, the strongest independent predictor of LVMinappr was BMI (p<0.0001). With adjustments for LV stress and other confounders there was a strong inverse relationship between LVMinappr and EF (partial r=-0.41, p<0.0001), whilst only modest inverse relations between LVM or LVMI and EF were noted (partial r=-0.07 to -0.09, p<0.05-0.09)(p<0.0001, comparison of partial r values). The independent relationship between LVMinappr and EF persisted with further adjustments for LVM or LVMI (partial r=-0.52, p<0.0001). LVMinappr and LV midwall fractional shortening were similarly inversely related (p<0.0001) and these relations were also stronger than and independent of LVM or LVMI. In conclusion, in a community sample with a high prevalence of obesity, inappropriate LVM is strongly and inversely related to variations in EF independent of and more closely than LVM or LVMI and BMI was the strongest independent determinant of inappropriate LVH. Therefore LVH is a compensatory response to workload, but when exceeding that predicted by workload, as may occur in obesity, is associated with LV systolic chamber decompensation. In 168 mild-to-moderate hypertensives treated for 4 months, although in patients with an LVMI>51g/m2.7 (n=112)(change in LVMI=-13.7±14.0 g/m2.7, p<0.0001), but not in patients with an LVMI≤51g/m2.7(n=56)(change in LVMI=1.3±9.3 g/m2.7) LVMI decreased with treatment; treatment failed to increase EF in either group (1.2±10.8% and 2.7±10.7% respectively). In contrast, in patients with inappropriate LVH (LVMinappr>150%, n=33) LVMinappr decreased (-32±27%, p<0.0001) and EF increased (5.0±10.3%, p<0.0001) after treatment, whilst in patients with a LVMinappr≤150% (n=135), neither LVMinappr (-0.5±23%), nor EF (0.9±10.3%) changed with therapy. With adjustments for circumferential LV wall stress and other confounders, whilst on-treatment decreases in LVM or LVMI were weakly related to an attenuated EF (partial r=0.17, p<0.05), on-treatment decreases in LVMinappr were strongly related to increases in EF even after further adjustments for LVM or LVMI (partial r=-0.63, confidence interval=-0.71 to -0.52, p<0.0001). In conclusion, decreases in LVMinappr are strongly related to on-treatment increases in EF beyond changes in LVM and LVMI. LVH can therefore be viewed as a compensatory change that preserves EF, but when in excess of that predicted by stroke work, as a pathophysiological process accounting for a reduced EF. In 478 participants of a randomly selected community sample with adjustments for waist circumference, age, sex, conventional systolic BP, diabetes mellitus or an HbA1c>6.1%, regular tobacco use, regular alcohol intake, pulse rate, and treatment for hypertension, an independent relationship between HOMA-IR and LVMinappr was noted (partial r=0.14, p<0.002). With further adjustments for either 24-hour systolic BP (partial r=0.11, p<0.05, n=351), aortic PWV (partial r=0.13, p<0.02, n=410), or circumferential LV wall stress (partial r=0.12, p<0.02, n=478) the independent relationship between HOMA-IR and LVMinappr also remained. Thus, the relationship between indices of an excess adiposity and LVM beyond haemodynamic factors may be explained in-part by insulin resistance. In conclusion, the results of the present thesis provide clarity on the process involved in the transition from obesity-associated LVH to LV dysfunction. In the present thesis I demonstrated that an index of central obesity explains a considerable proportion of the variation in LV diastolic function at a community level independent of LVM, LV remodelling and haemodynamic factors; that obesity-related increases in LVM exceeding that predicted by workload (LVMinappr) or alternative haemodynamic factors explains a marked proportion of variations in EF at a community level; that regression of LVMinappr is more closely associated with improvements in EF than LVM or LVM index (LVMI); and that obesity-associated insulin resistance may explain decreases in LV diastolic function and variations in LVMinappr and hence EF. Therefore, studies are warranted to evaluate the impact of interventions that improve insulin sensitivity on obesity-related decreases in LV diastolic function and increases in LVMinappr.

Thesis (M.Sc.(Med.)--University of the Witwatersrand, Faculty of Health Sciences, 2000.

Alterações sócio-econômicas, demográficas e epidemiológicas ocorridas nas últimas décadas resultaram em importantes modificações no perfil de morbi-mortalidade da população brasileira. Incluem-se neste cenário alterações do padrão nutricional da população, expressas pelo aumento da obesidade em adultos e pela redução da desnutrição em crianças. Isto implica questionarmos sobre a importância relativa dos problemas do balanço energético (desnutrição e obesidade), tanto em relação à magnitude quanto à determinação dos agravos nutricionais, com vistas a discutirmos intervenções de saúde e nutrição nos diferentes estratos da população. Visando aferir e qualificar o estágio da transição nutricional no país no final dos anos 80, estimamos e comparamos as freqüências da desnutrição e da obesidade na população brasileira de crianças entre 6 e 35 meses de idade (n=3641) e de adultos, ou seja, mulheres (n=15669) e homens (n=14235) da Pesquisa Nacional de Alimentação e Nutrição -PNSN-, realizada em 1989 pelo IBGE, através de amostra representativa dos domicílios do país. Desenvolvemos para tanto critérios comparáveis de avaliação do estado nutricional de mulheres, homens e crianças. Primeiramente, selecionamos índices antropométricos que expressassem a condição nutricional atual de adultos e crianças (Índice de Massa Corporal - IMC, no caso dos adultos e peso/idade e peso/altura, no caso das crianças). Adotamos o modelo normativo de diagnóstico da desnutrição e da obesidade em crianças e em adultos com o intuito de atribuir idêntica especificidade aos diagnósticos (valores críticos correspondentes aos percentis 5 e 95 das populações de referência). Para o diagnóstico da obesidade, os valores do IMC correspondem a 27,7 kg/m2 na população adulta feminina e 28,4 kg/m2 na população adulta masculina e para o diagnóstico da desnutrição os valores do IMC correspondem aos do percentil 5 nas diferentes idades. Para o conhecimento da natureza dos agravos nutricionais, nos valemos da análise da distribuição intra-familiar da desnutrição e da obesidade. Tal análise ficou restrita às famílias compostas por mãe, pai e pelo menos uma criança com idade entre 6 e 35 meses (n=2232). Utilizou-se a técnica de modelos log-lineares para testar as hipóteses de independência ou de associação entre o estado nutricional dos membros de uma mesma família. A ordenação das modalidades de desnutrição e obesidade, de acordo com a magnitude alcançada pelos problemas, revelou a obesidade em mulheres e a desnutrição em crianças, nesta ordem, como os principais problemas nutricionais do país. Os dois problemas são os mais prevalentes entre a população residente nas áreas urbanas das regiões Norte, Nordeste e Centro-Oeste e nas áreas rurais das regiões Sudeste e Centro-Oeste, apenas alternando a ordem entre si. Por outro lado, a obesidade é hegemônica em adultos e crianças das áreas urbanas das regiões Sudeste e Sul e do Sul rural. No Nordeste rural, ao contrário, a hegemonia é da desnutrição em crianças, homens e mulheres. A análise da distribuição intra-familiar da desnutrição indica que o problema tem natureza preponderantemente individual, ou seja, na maioria dos estratos estudados, a ocorrência da desnutrição em um dos membros da família não implica aumento do risco de desnutrição nos demais. Apenas entre as famílias em \"extrema pobreza\" (renda familiar inferior a 1/4 de salário mínimo per capita), detecta-se uma fraca associação entre a condição nutricional (desnutrição/não desnutridos) de seus membros. A análise da distribuição intra-familiar da obesidade também indica o problema como de ordem essencialmente individual. Somente entre as famílias de renda intermediária (renda familiar entre 1/2 e 1,O salário mínimo per capita) verifica-se associação entre a condição nutricional (obesidade/não obesos) de pais e mães. São várias as implicações dos achados deste estudo com relação ao desenho de políticas e programas nutricionais no Brasil. Destacam-se a maior prioridade que deveria merecer a prevenção e controle da obesidade em todas as classes sociais e a evidência de que o controle da desnutrição infantil deveria se fazer através de ações de saúde. Programas que incluam a distribuição generalizada de alimentos estariam justificados em estratos específicos da população. / Socio-economic, demographic and epidemiological changes which have occurred over recent decades have led to striking changes in the Brazilian population\'s morbidity and mortality pro files. This scenario includes changes in the nutritional patterns of the population, as evidenced by the increase in obesity among adults and the decrease in undernutrition children. This calls for a reevaluation of the relative importance of the problems of the energy balance (undernutrition and obesity) both as regards the magnitude and the cause of nutritional damage, with a view to discussing health and nutrition interventions in different strata of the population. In order to measure and qualify the stage of nutritional transition in the country at the end of the 1980s, we estimated and compared frequencies of undernutrition and obesity in the Brazilian population among children between 6 months and 35 months of age (n=3641) and adults,that is to say, in women (n=15669) and in men (n=14235), as registered in the National Health and Nutrition Survey (PNSN) of 1989, conducted by the IBGE (Brazilian Institute of Geography and Statistics), by means of a representative sample of households nationwide. We first selected anthropometric indices which express the current nutritional status of adults and children: the Body Mass Index - BMI for adults, and weight-for-age and weight-for-height for children. We adopted a normative model to diagnose undernutrition and obesity in children and adults with a view to ascribing identical specificity to the diagnoses (cut-offs corresponding to the 5th and 95th percentile of the reference). To diagnose obesity, the BMI values correspond to 27.7 kg/m2 and 28.4 kg/m2 female and male adult population, respectively, and to diagnose malnutrition the BMI values of 5th percentile at different ages among the adult population. In order to study the nutritional damage we made use the of the analysis o f intrafamiliar distribution o f undernutrition and obesity. This analysis was restricted to families comprising mother, father and at least one child between the ages of 6 months and 35 months (n=2232). The log-linear model technique was used to test the hypotheses of independence and association between the nutritional status of members of the family. Ordering the modalities of undernutrition and obesity, in accordance with the magnitude of the problems, showed obesity in women and undernutrition in children, in this order, to be the principal nutritional problems in Brazil. The two problems are the most frequent in the urban population ofthe north, northeast and center-west regions, and in the southeast and center-west rural regions, although they occasionaly change position. Obesity leads among adults and children in the urban areas of the southeast and south regions, and in the rural south. In the northeast rural area undernutrition leads among children, men and women. Analysis of intrafamily distribution of malnutrition indicates that the problems is overwhelmingly individual. That is to say, in most of the strata which were studied, malnutrition in one of the members of the family does not imply increased risk of malnutrition in the other family members. Only among families living in \"extreme poverty\" (family income below 1/4 minimum salaries per capita) cana weak association be detected between nutritional status (malnutrition/no malnutrition) in its members. Analysis in the intrafamily distributions of obesity also reveals the problem to be essentially individual. Only among middle-income families (family income between 1/2 and 1.0 salary per capita) can an association be detected between nutritional status (obesity/no obesity) of the parents (mother and father). The key implications of these findings have a bearing upon the planning ofthe nutrition politics and interventions in Brazil. The prevention and control of obesity should target the population of all the different social strata and the evidence of the control of children undernutrition should be mainly geared towards health actions. Programs which include widespread distribution of food would be justified in certain strata of the population.

Osteoarthritis (OA) is the most common degenerative joint disease affecting more than 40% of people above the age of 65 (Neogi et al., 2013). Obesity is one of the main risk factors of OA and has become a major problem in Western societies. With sedentary lifestyle and the aging of the population, it is estimated that more than 50% of British adults will be obese in 2030 (Wang et al., 2011). So far, the effect of obesity on joint degeneration has primarily been explained by the increased load on the joints. However, a growing number of studies have revealed that adipose tissue can affect cartilage and other joint tissues at a molecular level. The main goal of this thesis was to investigate the role of local knee joint tissues in obese patients with OA. The expression of molecular markers was investigated in local knee tissues: cartilage, synovium, infrapatellar fat pad (IPFP) and subchondral bone collected during Total Knee Replacement (TKR). A range of techniques (RT-PCR, Real Time qPCR, WB, IHC/ICC and ELISA) was used to examine the differences between genes and proteins expression in both lean and obese patients with OA. Further, the local immune cell infiltration was investigated in knee adipose tissue depots (synovium and IPFP) using flow cytometry. In addition, the subchondral bone microstructure was analysed using micro-Computed Tomography (μCT) and IHC techniques. Chondrocytes from OA patients were found to express a range of obesity-related genes. ADIPOR1 was produced significantly higher than ADIPOR2 in OA chondrocytes. Furthermore, CCL2 was produced at higher while PPARγ and visfatin were produced at a lower level in obese patients’ chondrocytes in comparison to lean ones. Synovium and IPFP also expressed a range of obesity-related genes. PPARγ and visfatin expression was lower in obese synovium and IPFP in comparison to lean. Surprisingly, adiponectin was expressed at a significantly lower level in obese patients’ synovium. In contrast, adiponectin was not differently expressed in lean and obese patients’ IPFP. The IPFP was found to be a significantly higher producer of PPARγ and adiponectin in comparison to synovium. Synovium, on the other hand, has an increased expression of VCAM-1, TLR4 and CCL2 in obese patients. An increased number of macrophages (defined by CD45+CD14+ and CD14+CD206+ markers expression) was detected in the synovium and IPFP from obese OA patients. Furthermore, there was an increased number of CD86+CD14+ cells in the synovium from obese patients. Other macrophage-related proteins including HLA-DR, CD36 were also expressed at a higher level in synovium from obese patients. T-lymphocyte detection revealed a higher number of CD3+CD4+ T cells in the synovium (but not IPFP) from obese patients but no change in the CD3+CD8+ population in both the synovium and IPFP. Subchondral bone analysis revealed possible differences in this tissue in obese male patients with OA in comparison to lean patients. μCT examination of subchondral bone showed a significantly lower bone mineral density (BMD) in obese in comparison to lean male OA patients. IHC analysis of bone sections suggested that there was an increased number of bone marrow adipose tissue macrophages. In addition, osteoblasts obtained from obese OA donors expressed a significantly higher level of ADIPOR2 and lower level of PPARγ mRNA in comparison to lean patients’ osteoblasts. The data obtained suggests that there were differences between lean and obese patients with OA at a molecular level. This proposes possible future directions for targeting these diseases. The limitation of the study were as follows: 1) possible different stages of end-stage OA between analysed patients, which could lead to differences in obtained data, 2) no non-OA control samples included in the study. However, the presented study may suggest that all tissues in the knee joint contribute to the interplay between OA and obesity. In addition, the data obtained is the first to suggest that there are differences in gene and protein expression in the synovium and IPFP from the same donor. Furthermore, there are differences in the immune cell populations in local adipose tissue depots (synovium and IPFP) from OA joints, which are linked to obesity. All of this data has helped to increase our understanding of the interaction between obesity and OA.

The empirical evidence concerning the associations between diet, particularly fat intake, and obesity is inconclusive. The aim of the present study was to investigate cross-sectional associations between general and central adiposity, and dietary and other socio-demographic and behavioural factors influencing energy balance. Study subjects were 961 women and 596 men aged 30-75 years who participated in the Greek segment of the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. General obesity was evaluated by Body Mass Index (BMI) and central obesity by Waist to Hip ratio (WHR) and Waist Circumference (WC). Dietary intake was estimated through a validated semi-quantitative Food Frequency Questionnaire (FFQ) obtained at baseline. Time weighted occupational and leisure activities, as well as socio-demographic and behavioural data were assessed through a life-style questionnaire. The methodological issues related to under-reporting and adjustment for energy intake have been considered in depth. Obesity indices (BMI, WHR, WC) were initially regressed, separately for men and women, on energy intake and energy expenditure, after adjusting for the confounding effects of age, socio-economic status and smoking habits and controlling for dietary under-reporting. Results indicated that increasing physical activity is less effective than decreasing energy intake in reducing BMI. WHR and WC were not affected by energy intake, whilst energy expenditure reduced WHR and WC independently of BMI. Obesity indices (BMI, WHR, WC) were subsequently regressed on nutrient intake after controlling for the confounding effects of energy intake, energy expenditure, age, socio- economic status and smoking habits, including and excluding under-reporters of energy intake. Among women, but not men, the nutrient more strongly positively associated to BMI was protein and to a lesser extent mono-unsaturated and total fat intake. WHR and WC do not seem to be differentially affected by energy equivalent amounts of energy generating nutrients.