The transtheoretical model and obesity: a bibliometric study

The Transtheoretical Model of behaviour change is currently one of the most promising models in terms of understanding and promoting behaviour change related to the acquisition of healthy living habits. By means of a bibliographic search of papers adopting a TTM approach to obesity, the present bibliometric study enables the scientific output in this field to be evaluated. The results obtained reveal a growing interest in applying this model to both the treatment of obesity and its prevention. Otherwise, author and journal outputs fit the models proposed by Lotka and Bradford, respectively.

Importance of early weight changes to predict long-term weight gain during psychotropic drug treatment.

BACKGROUND: Psychotropic drugs can induce substantial weight gain, particularly during the first 6 months of treatment. The authors aimed to determine the potential predictive power of an early weight gain after the introduction of weight gain-inducing psychotropic drugs on long-term weight gain. METHOD: Data were obtained from a 1-year longitudinal study ongoing since 2007 including 351 psychiatric (ICD-10) patients, with metabolic parameters monitored (baseline and/or 1, 3, 6, 9, 12 months) and with compliance ascertained. International Diabetes Federation and World Health Organization definitions were used to define metabolic syndrome and obesity, respectively. RESULTS: Prevalences of metabolic syndrome and obesity were 22% and 17%, respectively, at baseline and 32% and 24% after 1 year. Receiver operating characteristic analyses indicated that an early weight gain > 5% after a period of 1 month is the best predictor for important long-term weight gain (≥ 15% after 3 months: sensitivity, 67%; specificity, 88%; ≥ 20% after 12 months: sensitivity, 47%; specificity, 89%). This analysis identified most patients (97% for 3 months, 93% for 12 months) who had weight gain ≤ 5% after 1 month as continuing to have a moderate weight gain after 3 and 12 months. Its predictive power was confirmed by fitting a longitudinal multivariate model (difference between groups in 1 year of 6.4% weight increase as compared to baseline, P = .0001). CONCLUSION: Following prescription of weight gain-inducing psychotropic drugs, a 5% threshold for weight gain after 1 month should raise clinician concerns about weight-controlling strategies.

The association between obesity and back pain in nine countries: a cross-sectional study

BACKGROUND: The association between obesity and back pain has mainly been studied in high-income settings with inconclusive results, and data from older populations and developing countries are scarce. The aim of this study was to assess this association in nine countries in Asia, Africa, Europe, and Latin America among older adults using nationally-representative data. METHODS: Data on 42116 individuals ≥50 years who participated in the Collaborative Research on Ageing in Europe (COURAGE) study conducted in Finland, Poland, and Spain in 2011-2012, and the World Health Organization's Study on Global Ageing and Adult Health (SAGE) conducted in China, Ghana, India, Mexico, Russia, and South Africa in 2007-2010 were analysed. Information on measured height and weight available in the two datasets was used to calculate Body Mass Index (BMI). Self-reported back pain occurring in the past 30 days was the outcome. Multivariable logistic regression analysis was used to assess the association between BMI and back pain. RESULTS: The prevalence of back pain ranged from 21.5% (China) to 57.5% (Poland). In the multivariable analysis, compared to BMI 18.5-24.9 kg/m(2), significantly higher odds for back pain were observed for BMI ≥35 kg/m(2) in Finland (OR 3.33), Russia (OR 2.20), Poland (OR 2.03), Spain (OR 1.56), and South Africa (OR 1.48); BMI 30.0-34.0 kg/m(2) in Russia (OR 2.76), South Africa (OR 1.51), and Poland (OR 1.47); and BMI 25.0-29.9 kg/m(2) in Russia (OR 1.51) and Poland (OR 1.40). No significant associations were found in the other countries. CONCLUSIONS: The strength of the association between obesity and back pain may vary by country. Future studies are needed to determine the factors contributing to differences in the associations observed.

Results of surgical treatment of massive localized lymphedema in severely obese patients

OBJECTIVE: to evaluate the importance of treatment of deformities caused by massive localized lymphedema (MLL) in the severely obese. METHODS: in a period of seven years, nine patients with morbid obesity and a mean age of 33 years underwent surgical resection of massive localized lymphedema with primary synthesis. This is a retrospective study on the surgical technique, complication rates and improved quality of life. RESULTS: all patients reported significant improvement after surgery, with greater range of motion, ambulation with ease and more effective hygiene. Histological analysis demonstrated the existence of a chronic inflammatory process marked by lymphomonocitary infiltrate and severe tissue edema. We observed foci of necrosis, formation of microabscesses, points of suppuration and local fibrosis organization, and pachydermia. The lymphatic vessels and some blood capillaries were increased, depicting a framework of linfangiectasias. CONCLUSION: surgical treatment of MLL proved to be important for improving patients' quality of life, functionally rehabilitating them and optimizing multidisciplinary follow-up of morbid obesity, with satisfactory surgical results and acceptable complication rates, demonstrating the importance of treatment and awareness about the disease.

Treatment of gastrointestinal stromal tumor (GIST) during bariatric surgery

The gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor. One should pay special attention when the GIST comes in obese patients during surgery. The laparoscopic resections with standard techniques, such as gastric bypass, have been described with good results. However, GIST resection associated sleeve gastrectomy for the treatment of obesity is rare, but can be done safely, depending on the location of the tumor.

New perspectives on the melanocortins and their cardiovascular effects: Potential implications for the treatment of cardiovascular diseases with melanocortin analogues

The melanocortin peptides, including melanocyte-stimulating hormones, α-, β- and γ-MSH, are derived from the precursor peptide proopiomelanocortin and mediate their biological actions via five different melanocortin receptors, named from MC1 to MC5. Melanocortins have been implicated in the central regulation of energy balance and cardiovascular functions, but their local effects, via yet unidentified sites of action, in the vasculature, and their therapeutic potential in major vascular pathologies remain unclear. Therefore, the main aim of this thesis was to characterise the role of melanocortins in circulatory regulation, and to investigate whether targeting of the melanocortin system by pharmacological means could translate into therapeutic benefits in the treatment of cardiovascular diseases such as hypertension. In experiments designed to elucidate the local effects of α-MSH on vascular tone, it was found that α-MSH improved blood vessel relaxation via a nitric oxide (NO)-dependent mechanism without directly contracting or relaxing blood vessels. Furthermore, α-MSH was shown to regulate the expression and function of endothelial NO synthase in cultured human endothelial cells via melanocortin 1 receptors. In keeping with the vascular protective role, pharmacological treatment of mice with α-MSH analogues displayed therapeutic efficacy in conditions associated with vascular dysfunction such as obesity. Furthermore, α-MSH analogues elicited marked diuretic and natriuretic responses, which together with their vascular effects, seemed to provide protection against sodium retention and blood pressure elevation in experimental models of hypertension. In conclusion, the present results identify novel effects for melanocortins in the local control of vascular function, pointing to the potential future use of melanocortin analogues in the treatment of cardiovascular pathologies.

Alpha- and gamma-melanocyte stimulating hormones in obesity. A study of the key central areas of metabolic regulation

The melanocortin system is an important regulator of feeding, energy metabolism,and cardiovascular function and it consists of the pro-opiomelanocortin (POMC) derived melanocyte stimulating hormones (α-, β- and γ-MSH) and their endogenous melanocortin receptors, MC1R to MC5R. In the hypothalamus, α-MSH reduces food intake, and increases energy expenditure and sympathetic tone by binding to MC4R. Mutations affecting the MC4R gene lead to obesity in mammals. On the other hand, the metabolic effects of MC3R stimulation using agonists such as the endogenously expressed γ-MSH have been less extensively explored. The main objective of this study was to investigate the long-term effects of increased melanocortin tone in key areas of metabolic regulation in the central nervous system (CNS) in order to investigate the sitespecific roles of both α-MSH and γ-MSH. The aim was to stereotaxically induce local overexpression of single melanocortin peptides using lentiviral vectors expressing α-MSH (LVi-α-MSH-EGFP) and γ-MSH (LVi-γ-MSH-EGFP). The lentiviral vectors were shown to produce a long-term overexpression and biologically active peptides in cell-based assays. The LVi-α-MSHEGFP was targeted to the arcuate nucleus in the hypothalamus of diet induced obese mice where it reduced weight gain and adiposity independently of food intake. When the nucleus tractus solitarus in the brainstem was targeted, the LVi-α-MSH-EGFP treatment was shown to cause a small decrease in adiposity, which did not impact weight development. However, the α-MSH treatment increased heart rate, which was attenuated by adrenergic receptor blockade indicative of increased sympathetic activity. The LVi-γ-MSH-EGFP was targeted to the hypothalamus where it decreased fat mass in mice eating the standard diet, but the effect was abated if animals consumed a high-fat Western type diet. When the diet induced obese mice were subjected again to the standard diet, the LVi-γ-MSH-EGFP treated animals displayed increased weight loss and reduced adiposity. These results indicate that the long-term central anti-obesity effects of α-MSH are independent of food intake. In addition, overexpression of α-MSH in the brain stem efficiently blocked the development of adiposity, but increased sympathetic tone. The evidence presented in this thesis also indicates that selective MC3R agonists such as γ-MSH could be potential therapeutics in combination with low fat diets.

Mechanisms of endothelial dysfunction in obesity-associated hypertension

Obesity is strongly associated with high blood pressure, dyslipidemia, and type 2 diabetes. These conditions synergistically increase the risk of cardiovascular events. A number of central and peripheral abnormalities can explain the development or maintenance of high blood pressure in obesity. Of great interest is endothelial dysfunction, considered to be a primary risk factor in the development of hypertension. Additional mechanisms also related to endothelial dysfunction have been proposed to mediate the development of hypertension in obese individuals. These include: increase in both peripheral vasoconstriction and renal tubular sodium reabsorption, increased sympathetic activity and overactivation of both the renin-angiotensin system and the endocannabinoid system and insulin resistance. The discovery of new mechanisms regulating metabolic and vascular function and a better understanding of how vascular function can be influenced by these systems would facilitate the development of new therapies for treatment of obesity-associated hypertension.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Natural born weight gainers: The mechanisms of obesity in transgenic mice overexpressing neuropeptide Y

Neuropeptide Y (NPY) is a neurotransmitter promoting energy storage by activating Y-receptors and thus affecting food intake, thermogenesis and adipose tissue metabolism. NPY is expressed both in the central and sympathetic nervous system. Hypothalamic NPY is known to stimulate feeding, but the effects of noradrenergic neuron NPY are more ambiguous. Chronic stress stimulates fat accumulation via NPY release from noradrenergic neurons. Furthermore, polymorphism in the human Npy gene has been associated with metabolic disturbances and increased NPY secretion after sympathetic stimulation. The main objective of this study was to clarify the mechanisms of noradrenergic neuron NPY in the development of obesity. The metabolic phenotype of a homozygous mouse overexpressing NPY in the brain noradrenergic neurons and sympathetic nervous system (OE-NPYDβH mouse) was characterized. OE-NPYDβH mice had an increased fat mass and body weight, which caused impairments of glucose metabolism and hyperinsulinaemia with age. There were no differences in energy intake or expenditure, but the sympathetic tone was down-regulated and the endocannabinoid system activated. Furthermore, peripheral Y2-receptors in energy-rich conditions played an important role in mediating the fat-accumulating effect of NPY. These results indicate that noradrenergic neuron NPY promotes obesity via direct effects in the periphery and by modulating the sympatho-adrenal and endocannabinoid systems. Additionally, NPY in the central noradrenergic neurons is believed to possess many important roles. The phenotype of the OE-NPYDβH mouse resembles the situations of chronic stress and Npy gene polymorphism and thus these mice may be exploited in testing novel drug candidates for the treatment of obesity.

The potential role of the intestinal gut microbiota in obesity and the metabolic syndrome

The incidence of obesity has reached alarming levels worldwide, thus increasing the risk of development of metabolic disorders (e.g. type 2 diabetes, coronary heart disease (CHD) and cancer). Among the causes of obesity, diet and lifestyle play a central role. Although the treatment of obesity may appear quite straightforward, by simply re-addressing the balance between energy intake and energy expenditure, practically it has been very challenging. In the search for new therapeutic targets for treatment of obesity and related disorders, the gut microbiota and its activities have been investigated in relation to obesity. The human gut microbiota has already been shown to influence total energy intake and lipid metabolism, particularly through colonic fermentation of undigestible dietary constituents and production of short chain fatty acids (SCFA). Recent studies have highlighted the contribution of the gut microbiota to mammalian metabolism and energy harvested from the diet. A dietary modulation of the gut microbiota and its metabolic output could positively influence host metabolism and, therefore, constitute a potential coadjutant approach in the management of obesity and weight loss.

Calories, obesity and health in OECD countries

Theoretical models suggest that decisions about diet, weight and health status are endogenous within a utility maximization framework. In this article, we model these behavioural relationships in a fixed-effect panel setting using a simultaneous equation system, with a view to determining whether economic variables can explain the trends in calorie consumption, obesity and health in Organization for Economic Cooperation and Development (OECD) countries and the large differences among the countries. The empirical model shows that progress in medical treatment and health expenditure mitigates mortality from diet-related diseases, despite rising obesity rates. While the model accounts for endogeneity and serial correlation, results are affected by data limitations.

Progress in the genetics of common obesity and type 2 diabetes

The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.

Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers

Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.

On the evolutionary origins of obesity: a new hypothesis

Obesity is an escalating threat of pandemic proportions, currently affecting billions of people worldwide and exerting a devastating socioeconomic influence in industrialized countries. Despite intensive efforts to curtail obesity, results have proved disappointing. Although it is well recognized that obesity is a result of gene-environment interactions and that predisposition to obesity lies predominantly in our evolutionary past, there is much debate as to the precise nature of how our evolutionary past contributed to obesity. The “thrifty genotype” hypothesis suggests that obesity in industrialized countries is a throwback to our ancestors having undergone positive selection for genes that favored energy storage as a consequence of the cyclical episodes of famine and surplus after the advent of farming 10 000 years ago. Conversely, the “drifty genotype” hypothesis contends that the prevalence of thrifty genes is not a result of positive selection for energy-storage genes but attributable to genetic drift resulting from the removal of predative selection pressures. Both theories, however, assume that selection pressures the ancestors of modern humans living in western societies faced were the same. Moreover, neither theory adequately explains the impact of globalization and changing population demographics on the genetic basis for obesity in developed countries, despite clear evidence for ethnic variation in obesity susceptibility and related metabolic disorders. In this article, we propose that the modern obesity pandemic in industrialized countries is a result of the differential exposure of the ancestors of modern humans to environmental factors that began when modern humans left Africa around 70 000 years ago and migrated through the globe, reaching the Americas around 20 000 years ago. This article serves to elucidate how an understanding of ethnic differences in genetic susceptibility to obesity and the metabolic syndrome, in the context of historic human population redistribution, could be used in the treatment of obesity in industrialized countries