Sensing and control of adipocyte function

Obesity has become a global epidemic. Approximately 15% of the world population is either overweight or obese. This figure rises to 75% in many westernised countries including the United Kingdom. Health costs in the UK to treat obesity and associated disease are conservatively estimated at 6% of the National Health Service (NHS) budget equating to 3.33 billion Euros. Excess adiposity, especially in visceral depots, increases the risk of type 2 diabetes, cardiovascular disease, gall stones, hypertension and cancer. Type 2 diabetes mellitus accounts for >90% of all cases of diabetes of which the majority can be attributed to increased adiposity, and approximately 70% of cardiovascular disease has been attributed to obesity in the US. Weight loss reduces risk of these complications and in some cases can eliminate the condition. However, weight loss by conventional non-medicated methods is often unsuccessful or promptly followed by weight regain. This thesis has investigated adipocytes development and adipokine signalling with a view to enhance the understanding of tissue functionality and to identify possible targets or pathways for therapeutic intervention. Adipocyte isolation from human tissue samples was undertaken for these investigative studies, and the methodology was optimised. The resulting isolates of pre-adipocytes and mature adipocytes were characterised and evaluated. Major findings from these studies indicate that mature adipocytes undergo cell division post terminal differentiation. Gene studies indicated that subcutaneous adipose tissue exuded greater concentrations and fluctuations of adipokine levels than visceral adipose tissue, indicating an important adiposensing role of subcutaneous adipose tissue. It was subsequently postulated that the subcutaneous depot may provide the major focus for control of overall energy balance and by extension weight control. One potential therapeutic target, 11ß-hydrosteroid dehydrogenase (11ß-HSD1) was investigated, and prospective inhibitors of its action were considered (BVT1, BVT2 and AZ121). Selective reduction of adiposity of the visceral depot was desired due to its correlation with the detrimental effects of obesity. However, studies indicated that although the visceral depot tissue was not unaffected, the subcutaneous depot was more susceptible to therapeutic inhibition by these compounds. This was determined to be a potentially valuable therapeutic intervention in light of previous postulations regarding long-term energy control via the subcutaneous tissue depot.

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

Aims - A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. Methods - We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged = 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. Results - In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24–0.67) kg/m2 per A-allele (P = 3.0 × 10-5) and with waist circumference was 0.88 (95% CI 0.36–1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07–1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14–1.31); P = 1.07 × 10-8] even after adjusting for BMI [1.18 (95% CI 1.10–1.27); P = 1.02 × 10-5] or waist circumference [1.18 (95% CI 1.10–1.27); P = 3.97 × 10-5]. Conclusions - The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

The role of adipokines in beta-cell failure of type 2 diabetes

Beta-cell failure coupled with insulin resistance is a key factor in the development of type 2 diabetes. Changes in circulating levels of adipokines, factors released from adipose tissue, form a significant link between excessive adiposity in obesity and both aforementioned factors. In this review we consider the published evidence for the role of individual adipokines on the function, proliferation, death and failure of beta-cells, focusing on those reported to have the most significant effects (leptin, adiponectin, TNFa, resistin, visfatin, DPP-IV and apelin). It is apparent that some adipokines have beneficial effects whereas others have detrimental properties; the overall contribution to beta-cell failure of changed concentrations of adipokines in the blood of obese pre-diabetic subjects will be highly dependent on the balance between these effects and the interactions between the adipokines which act on the beta-cell via a number of intersecting intracellular signalling pathways. We emphasise the importance, and comparative dearth, of studies into the combined effects of adipokines on beta-cells.

Obesity in the pathogenesis of type 2 diabetes

Obesity, and especially visceral adiposity, escalates the development of insulin resistance and type 2 diabetes. Excess adipose tissue contributes to a chronic increase in circulating fatty acids reducing the usage of glucose as a source of cellular energy. Excess fatty acids also result in increased deposition of fat in muscle and liver, and increased metabolites such as diacylglycerol and ceramide which activate isoforms of protein kinase C that impede cellular insulin signalling. Chronically raised lipid levels also impair islet beta cell function, acting in conjuction with insulin resistance to aggravate hyperglycaemia. The detrimental effects of several adipokines such as TNF, IL6 and RBP4, which are produced in excess by an increased adipose mass, and reduced production of adiponectin are further mechanisms through which obesity potentiates the development of type 2 diabetes. © 2011 The Author(s).

Zinc-α2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia

Zinc-α2-glycoprotein (ZAG), a 43-kDa protein, is overexpressed in certain human malignant tumors and acts as a lipid-mobilizing factor to stimulate lipolysis in adipocytes leading to cachexia in mice implanted with ZAG-producing tumors. Because white adipose tissue (WAT) is an endocrine organ secreting a wide range of protein factors, including those involved in lipid metabolism, we have investigated whether ZAG is produced locally by adipocytes. ZAG mRNA was detected by RT-PCR in the mouse WAT depots examined (epididymal, perirenal, s.c., and mammary gland) and in interscapular brown fat. In WAT, ZAG gene expression was evident in mature adipocytes and in stromal-vascular cells. Using a ZAG Ab, ZAG protein was located in WAT by Western blotting and immunohistochemistry. Mice bearing the MAC16-tumor displayed substantial losses of body weight and fat mass, which was accompanied by major increases in ZAG mRNA and protein levels in WAT and brown fat. ZAG mRNA was detected in 3T3-L1 cells, before and after the induction of differentiation, with the level increasing progressively after differentiation with a peak at days 8-10. Both dexamethasone and a β 3 agonist, BRL 37344, increased ZAG mRNA levels in 3T3-L1 adipocytes. ZAG gene expression and protein were also detected in human adipose tissue (visceral and s.c.). It is suggested that ZAG is a new adipose tissue protein factor, which may be involved in the modulation of lipolysis in adipocytes. Overexpression in WAT of tumor-bearing mice suggests a local role for adipocyte-derived ZAG in the substantial reduction of adiposity of cancer cachexia.

Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein or LPD (9% casein for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03 and increased male offspring weight (P = 0.009 were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P <0.02. However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg and elevated heart rate (P <0.05, whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk, LPD males had elevated adiposity (P = 0.04, reduced heart-to-body weight ratio (P = 0.04, and elevated circulating TNF-α levels (P = 0.015 compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb and metabolism (Fto in LPD offspring (P <0.03. These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring

Purpose: Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Methods: Female MF-1 mice were fed a normal protein (NP, 18 % casein) or a protein-restricted (PR, 9 % casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45 % kcal fat) or standard chow (C, 7 % kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7-11 per group). Results: PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P <0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P <0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P <0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. Conclusions: These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood. © 2014 Springer-Verlag Berlin Heidelberg.

Parental diet, pregnancy outcomes and offspring health:metabolic determinants in developing oocytes and embryos

The periconceptional period, embracing the terminal stages of oocyte growth and post-fertilisation development up to implantation, is sensitive to parental nutrition. Deficiencies or excesses in a range of macro- and micronutrients during this period can lead to impairments in fertility, fetal development and long-term offspring health. Obesity and genotype-related differences in regional adiposity are associated with impaired liver function and insulin resistance, and contribute to fatty acid-mediated impairments in sperm viability and oocyte and embryo quality, all of which are associated with endoplasmic reticulum stress and compromised fertility. Disturbances to maternal protein metabolism can elevate ammonium concentrations in reproductive tissues and disturb embryo and fetal development. Associated with this are disturbances to one-carbon metabolism, which can lead to epigenetic modifications to DNA and associated proteins in offspring that are both insulin resistant and hypertensive. Many enzymes involved in epigenetic gene regulation use metabolic cosubstrates (e.g. acetyl CoA and S-adenosyl methionine) to modify DNA and associated proteins, and so act as 'metabolic sensors' providing a link between parental nutritional status and gene regulation. Separate to their genomic contribution, spermatozoa can also influence embryo development via direct interactions with the egg and by seminal plasma components that act on oviductal and uterine tissues. © IETS 2014.

Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age

Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P&0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health. © 2011 Watkins et al.

Resistin down-regulates insulin receptor expression, and modulates cell viability in rodent pancreatic beta-cells

The adipokine resistin is known to induce insulin resistance in rodent tissues. Increases in adipose tissue mass are known to have a negative effect on pancreatic beta-cell function, although the mechanisms are poorly understood. This study investigated the effects of resistin on insulin secretion, insulin receptor expression and cell viability in pancreatic beta-cells. BTC-6 or BRIN-BD11 cells were treated for 24h with resistin, and insulin receptor expression, insulin secretion and cell viability were measured. Incubation with 40ng/ml resistin caused significant decreases in insulin receptor mRNA and protein expression, but did not affect insulin secretion. At low concentrations, resistin caused significant increases in cell viability. These data implicate resistin as a factor that may regulate beta-cell function/viability, and suggests a potential mechanism by which increased adiposity causes beta-cell dysfunction.

New biomarkers and risk stratification in atrial fibrillation:simplicity and practicality matter

Advances in our understanding of pathological mechanisms can inform the identification of various biomarkers for risk stratification, monitoring drug efficacy and toxicity; and enabling careful monitoring of polypharmacy. Biomarkers in the broadest sense refer to 'biological markers' and this can be blood-based (eg. fibrin D-dimer, von Willebrand factor, etc) urine-based (eg. thromboxane), or even related to cardiac or cerebral imaging(1). Most biomarkers offer improvements over clinical risk scores in predicting high risk patients - at least statistically - but usually at the loss of simplicity and practicality for easy application in everyday clinical practice. Given the various biomarkers can be informed by different aspects of pathophysiology (e.g. inflammation, clotting, collagen turnover) they can nevertheless contribute to a better understanding of underlying disease processes(2). Indeed, many age-related diseases share common modifiable underpinning mechanisms e.g. inflammation, oxidative stress and visceral adiposity.

Ageing, adipose tissue, fatty acids and inflammation

A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

Prevalência e fatores associados à diminuição da função pulmonar em obesos em pré-operatório de cirurgia bariátrica

Introduction: Obesity shows changes in pulmonary function and respiratory mechanics, however, little is known regarding the prevalence of worsening respiratory function when considering the increase in central or peripheral adiposity or general obesity. Objectives: To analyze the association between anthropometric adiposity and decreased lung function in obese. Materials and Methods: Patients eligible for this study obese individuals (IMC≥30kg/m2) in pre-bariatric surgery and referred for Treatment Clinic of Obesity and Related Diseases, located at the University Hospital Onofre Lopes (HUOL), from October 2005 and July 2014. The evaluation included clinical information and measurement of anthropometric measures (body mass index (BMI), body fat index (BFI) and waist circumference (WC) and neck (NC)) and spirometric. The prevalence and analysis by Poisson regression was performed considering the following outcome variables: forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and Maximum Voluntary Ventilation (MVV) and as predictor variables were considered: BMI, IAC, WC and NC and as control variables: age, gender, smoking history and comorbidities (diabetes mellitus, dyslipidemia and hypertension). Statistical analysis was performed using Statistical Package for Social Sciences software (SPSS - version 20.0). Results: We analyzed 384 individuals, 75% women, mean BMI: 46.6 (± 8.7) kg/m2, IAC: 49.26 (± 9.48)%, WC: 130.84 (± 16.23) cm and NC: 42.3 (± 4.6) cm. The higher prevalence of FVC and FEV1 <80% was observed in individuals with NC above 42 cm, followed those with a BMI above 45 kg/m2. Multivariate analysis using Poisson regression showed as risk factors associated with FVC <80%, the variables: NC above 42 cm (odds ratio (OR) 2.41) and BMI over 45Kg/m2 (OR 1.71 ). As for FEV1 <80% predicted, all predictor variables were associated, with the largest odds presented by the NC (3.40). MVVV was not associated with any studied varaible. Conclusion: Individuals with NC above 42 cm had higher prevalence of reduced lung function and the NC was the measure with the highest association with reduced lung function in obese.

Avaliação do efeito do liraglutida nos tecidos muscular e adiposo e nos parâmetros bioquímicos em camundongos Swiss submetidos à dieta de cafeteria e a atividade física

Obesity is a chronic metabolic disease characterized by adipose tissue formation excess leading to an increase in body fat mass, of multifactorial origin, produced mainly by poor eating habits combined with a sedentary lifestyle. Data consider obesity as a serious disease that affects the world's population, ranking fifth in death rates. Faced with this situation, individuals seek, increasingly, means to lose weight with less physical effort and food. In 2009 and 2010 the drug liraglutide was lauched in order to reduce weight in individuals with diabetes mellitus type 2, thus avoiding the emergence of other diseases. The aggravating factor is that obese nondiabetic individuals are making use of this substance, even if its use is not authorized by ANVISA (Brazilian Health Surveillance Agency). Thus the objective of this research is to evaluate the effect of liraglutide for muscle or fat tissues and biochemical parameters in Swiss mice submitted to cafeteria diet and physical activity. The study was approved by the Ethics Committee on Animal Use - CEUA (nº003 Protocol / 2014). For this study 74 animals (Swiss mice) were used, divided as follows: in the initial phase of this study, we carried out a pilot study (n = 10) divided into a control group (PCON) (n = 5) and cafeteria group (PCAF) (n = 5), in order to evaluate a cafeteria diet which was both attractive to the animals and that could provide an increase in adipose tissue. After the induction of the diet, animals were euthanized and as a result, the animals in the PCAF group showed an intra-abdominal adiposity 0.74 ± 0.05 g, taken as the parameter for increasing fat in animals. Subsequently the study base was conducted for this research where animals were used (n = 64) divided into 2 groups: the Cafeteria Study Base Group (EBCAF) divided as follows: cafeteria + exercise + liraglutide (CEL) (n = 8), cafeteria + exercise + saline (CES) (n = 8), cafeteria + liraglutide (CL) (n = 8) and cafeteria + saline (CS) (n = 8). The Chow Study Base group (EBR) was divided into: exercise + liraglutide (EL) (n = 8), exercise + saline + (ES) (n = 8), liraglutide (L) (n = 8) and saline solution (SS) (n = 8). All animals went through the submission process to the cafeteria diet, followed by exercise protocol through swimming and treatment with the test substance intraperitoneally (200 mg / mL / kg). After the treatments, the animals were euthanized and had the following parameters evaluated: the muscle tissue mass, adipose tissue mass and biochemical parameters. It was observed that the processing done with the exercise-associated liraglutide reduced adipose tissue mass significantly (0.32 ± 0.05 g) compared to the saline group (0.53 ± 0.07 g). There were no changes in the muscle tissue of the group which was treated and exercised (1.39 ± 0.03 g) compared to the saline group (1.33 ± 0.03 g). Regarding biochemical parameters it was evident that there were changes in these parameters. Interesting to note that, although blood glucose values have been changed, the animals did not become diabetic. Thus, it appears that physical activity together with liraglutide is eficcient to the loss of intraabdominal adipose tissue and the maintenance of lean body mass thereby generating a satisfactory result in the pursuit of quality of life and disease prevention.

Avaliação do efeito do liraglutida nos tecidos muscular e adiposo e nos parâmetros bioquímicos em camundongos Swiss submetidos à dieta de cafeteria e a atividade física

Obesity is a chronic metabolic disease characterized by adipose tissue formation excess leading to an increase in body fat mass, of multifactorial origin, produced mainly by poor eating habits combined with a sedentary lifestyle. Data consider obesity as a serious disease that affects the world's population, ranking fifth in death rates. Faced with this situation, individuals seek, increasingly, means to lose weight with less physical effort and food. In 2009 and 2010 the drug liraglutide was lauched in order to reduce weight in individuals with diabetes mellitus type 2, thus avoiding the emergence of other diseases. The aggravating factor is that obese nondiabetic individuals are making use of this substance, even if its use is not authorized by ANVISA (Brazilian Health Surveillance Agency). Thus the objective of this research is to evaluate the effect of liraglutide for muscle or fat tissues and biochemical parameters in Swiss mice submitted to cafeteria diet and physical activity. The study was approved by the Ethics Committee on Animal Use - CEUA (nº003 Protocol / 2014). For this study 74 animals (Swiss mice) were used, divided as follows: in the initial phase of this study, we carried out a pilot study (n = 10) divided into a control group (PCON) (n = 5) and cafeteria group (PCAF) (n = 5), in order to evaluate a cafeteria diet which was both attractive to the animals and that could provide an increase in adipose tissue. After the induction of the diet, animals were euthanized and as a result, the animals in the PCAF group showed an intra-abdominal adiposity 0.74 ± 0.05 g, taken as the parameter for increasing fat in animals. Subsequently the study base was conducted for this research where animals were used (n = 64) divided into 2 groups: the Cafeteria Study Base Group (EBCAF) divided as follows: cafeteria + exercise + liraglutide (CEL) (n = 8), cafeteria + exercise + saline (CES) (n = 8), cafeteria + liraglutide (CL) (n = 8) and cafeteria + saline (CS) (n = 8). The Chow Study Base group (EBR) was divided into: exercise + liraglutide (EL) (n = 8), exercise + saline + (ES) (n = 8), liraglutide (L) (n = 8) and saline solution (SS) (n = 8). All animals went through the submission process to the cafeteria diet, followed by exercise protocol through swimming and treatment with the test substance intraperitoneally (200 mg / mL / kg). After the treatments, the animals were euthanized and had the following parameters evaluated: the muscle tissue mass, adipose tissue mass and biochemical parameters. It was observed that the processing done with the exercise-associated liraglutide reduced adipose tissue mass significantly (0.32 ± 0.05 g) compared to the saline group (0.53 ± 0.07 g). There were no changes in the muscle tissue of the group which was treated and exercised (1.39 ± 0.03 g) compared to the saline group (1.33 ± 0.03 g). Regarding biochemical parameters it was evident that there were changes in these parameters. Interesting to note that, although blood glucose values have been changed, the animals did not become diabetic. Thus, it appears that physical activity together with liraglutide is eficcient to the loss of intraabdominal adipose tissue and the maintenance of lean body mass thereby generating a satisfactory result in the pursuit of quality of life and disease prevention.