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Objective This study aimed to investigate human adenovirus 36 (Adv36) as an associated factor for adiposity in children and adolescents aged 9–12 years. Methods This was a case-control study comparing overweight (cases) and eutrophic (controls) children and adolescents aged 9–12 years based on their body mass index in relation to human adenovirus 36 serology. Human adenovirus 36-specific neutralizing antibodies were assessed using the serum neutralization assay, and a questionnaire regarding the subjects’ personal backgrounds, breastfeed history, age of starting daycare, and eating and exercise habits was also applied. Results A total of 101 (51, eutrophic; 50, overweight) children were included in the study. The Adv36 seropositivity rate was of 15.8%, which increased the chance of being overweight by 3.17 times (p = 0.049). Enrollment in a full-time daycare center before the age of 24 months increased the chance of being overweight by 2.78 times (p = 0.027). Metabolic parameters (total cholesterol and blood glucose) were insignificantly different among children who were seropositive or seronegative for human adenovirus 36. Conclusion This study concluded that excessive weight was positively associated with seropositivity for human adenovirus 36. Early enrollment in a full-time daycare was also an associated factor for obesity. Such data, confirmed in new studies, reinforces the role of human adenovirus 36 in the increase of childhood adiposity.

INTRODUCTION Obesity has numerous etiologies and includes biological factors. Studies have demonstrated that the human adenovirus subtype 36 (Adv36) is an adipogenic agent and causes metabolic alterations. Study results on the prevalence of Adv36 and clinical effects in humans vary substantially. This was a systematic review to summarize the studies on the prevalence of Adv36 infection and its association with human obesity. METHODS A systematic literature review was conducted using the preferred reporting items for systematic reviews and meta-analysis (PRISMA). Observational or experimental studies found in the Medline, Embase, LILACS, Science Direct and SciELO databases that presented results on the prevalence of Adv36 in humans were included. RESULTS Thirty-seven studies were screened. A total of 10,300 adults aged 18-70 years and 4585 children and adolescents aged 3-18 years were assessed. The average prevalence of Adv36 among adults was 22.9%, ranging from 5.5% to 49.8%. Among children and adolescents, the average prevalence of Adv36 was 28.9%, ranging from 7.5% to 73.9%. There was a positive statistical relationship between Adv36 and weight gain, obesity, or metabolic changes in 31 studies. However, in four studies there was no association with obesity, and in one, no association was described. One of the studies showed an inverse correlation, i.e., Adv36 was a protective factor against obesity. CONCLUSION Strong evidence suggested a positive association between viral infection and obesity. However, due to the multi-causality of obesity and heterogeneity of studies, diagnostic tests should be standardized and easily accessible by the population to estimate the overall prevalence of Adv36 infection and its association with obesity.

The vitamin status of a child depends on many factors and most of the clinical studies do not take into account the different access to adequate nutrition of children coming from different countries and the consequent major differences in micronutrients or vitamin deficits between low-income and high-income countries. Vitamin supplements are included in the general field of dietary supplements. There is a large amount of not always factual material concerning vitamin supplements, and this may sometimes create confusion in clinicians and patients. Inadequate information may lead to the risk of attributing beneficial properties leading to their over-use or misuse in the paediatric field. Vitamin supplementation is indicated in all those conditions in which a vitamin deficiency is found, either because of a reduced intake due to reduced availability of certain foods, restrictive diets or inadequate absorption. The lack of guidelines in these fields may lead paediatricians to an improper use of vitamins, both in terms of excessive use or inadequate use. This is due to the fact that vitamin supplementation is often intended as a therapy of support rather than an essential therapeutic tool able to modify disease prognosis. In fact, various vitamins and their derivatives have therapeutic potential in the prevention and treatment of many diseases, especially in emerging conditions of paediatric age such as type 2 diabetes and the metabolic syndrome. The aim of the present article is to analyse the state of the art and consider new perspectives on the role of vitamin supplements in children.

Prior infection with adenovirus 36 (Adv36) has been associated with increased adiposity, improved insulin sensitivity, and a lower prevalence of diabetes. This study investigated the prevalence of Adv36 seropositivity and its association with obesity and diabetes among adults attending a diabetes centre in the UAE.Participants (N = 973) with different weight and glucose tolerance categories were recruited. Adv36 seropositivity (Adv36 + ) was assessed using ELISA. Differences among groups were analyzed using statistical tests as appropriate to the data. Prevalence of Adv36+ in the study population was 47%, with no significant difference in obese and non-obese subgroups (42.5% vs 49.6% respectively; p=non-significant). Females were more likely to be Adv36+ compared to males (odds ratio 1.78; 95% CI 1.36–2.32, p

The dramatic increase of people affected by obesity worldwide seems to be influenced by external factors independent of eating habits, physical exercise, or genetic characteristics. There may be a number of such factors, but one hypothesis is that there is person-to-person transmission, causing an epidemic effect, as occurs with infectious diseases. In animal models, experimental infection with human adenovirus-36 (Adv36) causes obesity. Humans cannot be experimentally infected, but a number of studies found a correlation of positive serology for Adv36 with overweight/obesity in humans. In vitro studies have shown that Adv36 accelerates the differentiation and proliferation of preadipocytes into adipocytes and increases their lipid concentration. Another viral mechanism involved is the activation of a noninsulin-dependent process that increases glucose uptake, mainly in adipose tissue and muscle. The increased glucose, coupled with increased lipogenesis due to increased fatty acid synthase and the action of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in stimulating adipocyte differentiation from adult stem cells enhances fat accumulation within the adipocytes. In studies conducted to date, the Adv36 E4 open reading frame 1 gene (E4orf1), which activates the glucose transporter protein isoform 4 (GLUT4) and glucose transporter protein isoform 1 (GLUT1) glucose transporters, appears to play a major role in the virus adipogenesis. The aim of this study was to review the pathophysiology of obesity and the role of Adv36.

Introduction: Exposure to food odors are known to increase food intake. Olfaction declines from age 50 years. Objective: We examined changes in the sense of smell, body weight, food preferences, and parameters of metabolic status, following the use of a specially designed nasal device. Methods: This is a randomized, placebo-controlled study. Participants wore a nasal device (soft silicone insert) for 5–12 h daily (device group) or inserted 2 drops of normal saline into each nostril daily (control group). Follow-up visits occurred every 2 weeks. All participants were given a 500 kcal/day reduced diet and instructed not to change their regular physical activity. Weight, food preferences, olfactory sensitivity, and blood tests were performed at baseline and after 12 weeks. Results: Of 156 participants, 65 (42%) completed the study. Sense of smell decreased in the device group (from 6.4 ± 0.9 to 4.4 ± 1.5, on a scale of 0–7, p < 0.001), and did not change in the control group. Weight loss decreased by 6.6 ± 3.7% (p = 0.001) and by 5.7 ± 3.5% (p = 0.001) in the respective groups (between-group difference, p > 0.05). Among participants aged ≤50 years, weight loss was greater in the device than in the control group (7.7 ± 4.2% vs. 4.1 ± 2.9%, p = 0.02). Insulin level and the homeostatic model assessment of insulin resistance (HOMA-IR) were significantly reduced in the device group (p = 0.02 and p = 0.01, respectively), but not in the control group. Food preferences for sugar (p < 0.02), sweet beverages (p < 0.001), and artificial sweeteners (p < 0.02) were significantly reduced in the device group compared to the control group. Conclusions: The use of a novel self-administrated nasal device led to reduced olfactory sensitivity, improved insulin sensitivity, weight loss, and lesser preference for sweets in adults aged ≤50 years.

IntroductionAthletes and military personnel are both at risk of disabling injuries due to extreme physical activity. A method to predict which individuals might be more susceptible to injury would be valuable, especially in the military where basic recruits may be discharged from service due to injury. We postulate that certain body characteristics may be used to predict risk of injury with physical activity.MethodsUS Army basic training recruits between the ages of 17 and 21 (N = 17,680, 28% female) were scanned for uniform fitting using the 3D body imaging scanner, Human Solutions of North America at Fort Jackson, SC. From the 3D body imaging scans, a database consisting of 161 anthropometric measurements per basic training recruit was used to predict the probability of discharge from the US Army due to injury. Predictions were made using logistic regression, random forest, and artificial neural network (ANN) models. Model comparison was done using the area under the curve (AUC) of a ROC curve.ResultsThe ANN model outperformed two other models, (ANN, AUC = 0.70, [0.68,0.72], logistic regression AUC = 0.67, [0.62,0.72], random forest AUC = 0.65, [0.61,0.70]).ConclusionsBody shape profiles generated from a three-dimensional body scanning imaging in military personnel predicted dischargeable physical injury. The ANN model can be programmed into the scanner to deliver instantaneous predictions of risk, which may provide an opportunity to intervene to prevent injury.

In their comprehensive review on adenoviruses, Khanal et al. omitted obesity as a disease caused by adenovirus 36 (Adv36). Animal studies have shown that experimental infection with Adv36 causes increased adiposity, and human association studies have shown that prior infection with Adv36 is correlated with greater body weight in humans in multiple countries of the world.

Objective This study aimed to evaluate some potential mechanisms of effects of natural honey on locomotor activity, energy intake, changes in body weight, and hepatic expression of three genes of fat metabolism: fatty acid binding protein 1 (Fabp1), hepatic lipase (Lipc), and apolipoprotein A1 (Apoa1). Methods Male Wistar rats were fed high fat diet (HFD) (n = 18) or normal diet (ND) (n = 18) for 4 weeks, then treated daily with saline (Group1,n = 6), honey 1 g/kg (Group2,n = 6), & honey 2 g/kg (Group3,n = 6)), for another 4 weeks, continuing on HFD or ND. Food intake, changes in body weight and locomotor activity were monitored weekly. Levels of circulating lipids, glucose, and liver enzymes were determined at sacrifice. The expression of Fabp1, Lipc, and Apoa1 genes were determined through real time-qPCR. Results Treatment with high and low doses of honey significantly reduced body weight-gain in HFD as well as ND treated rats compared to saline treated controls. The honey treatment lowered TAG, TC, LDL, VLDL levels (P Conclusion Adverse effects of HFD on body weight-gain, serum lipids profile, serum glucose, and liver steatosis are reversed by honey treatment in rats. Studies of honey treatment for metabolic syndrome in humans are indicated.

Human adenovirus-36 (Adv36) increases adiposity, but also upregulates distal insulin signaling in vitro in human adipose and muscle tissue and in vivo in the rodent independently of adiposity. Accordingly, healthy adults and children with antibodies against Adv36 had increased insulin sensitivity and reduced hepatic lipid accumulation. We hypothesized that Adv36 infection would be less frequent in individuals with type 2 diabetes or impaired glycemic control.Presence of antibodies against Adv36 was analyzed for association to type 2 diabetes or impaired glycemic control in a two-wave population-based sample of well-characterized adults (n = 1734). Indices of impaired glycemic control included oral glucose tolerance, and circulating fasting levels of glucose, insulin, and insulin-like growth factor binding protein-1 (IGFBP-1).Adv36 seropositivity was more common in those with normal glucose tolerance (NGT) than in those with diabetes (females: OR 17.2, 95% CI 4.0-74.3; males: OR 3.5, 95% CI 1.8-6.7). Also, females with NGT had higher frequency of Adv36 seropositivity than females with prediabetes (impaired glucose tolerance and/or impaired fasting glucose; OR 1.8, 95% CI 1.1-3.1). Within the female prediabetes group Adv36 seropositivity was associated with higher insulin sensitivity reflected by reduced HOMA-IR and increased IGFBP-1.Adv36 infection is associated with lower occurrence of type 2 diabetes and better insulin sensitivity in adults, particularly among females.

Obesity is associated with numerous metabolic comorbidities. Weight loss is an effective measure for alleviating many of these metabolic abnormalities. However, considering the limited success of most medical weight-management approaches in producing a sustained weight loss, approaches that improve obesity-related metabolic abnormalities independent of weight loss would be extremely attractive and of practical benefit. Metabolically healthy obesity supports the notion that a better metabolic profile is possible despite obesity. Moreover, adequate expansion of adipose tissue appears to confer protection from obesity-induced metabolic comorbidities. To this end, the 10th Stock conference examined new approaches to improve metabolic comorbidities independent of weight loss. In particular, human adenovirus 36 (Ad36) and specific gut microbes were examined for their potential to influence lipid and glucose homeostasis in animals and humans. While these microbes possess some undesirable properties, research has identified attributes of adenovirus Ad36 and gut microbes that may be selectively harnessed to improve metabolic profile without the obligatory weight loss. Furthermore, identifying the host signalling pathways that these microbes recruit to improve the metabolic profile may offer new templates and targets, which may facilitate the development of novel treatment strategies for obesity-related metabolic conditions.

Dermatofibrosarcoma protuberans (DFSP) is rare in the hand and even rarer in the digits with only two previous reports in the literature, one involving a middle finger and the other a thumb. We present the case of a 31-year-old police officer with DFSP on the dorsum of the middle phalanx of his non-dominant ring finger. The patient underwent amputation of the finger at the level of the metacarpophalangeal joint considering the need for wide local excision of DFSP to prevent recurrence. The level was also chosen to maximise the functional recovery of the patient considering the physical aspects of his profession.

The macrogeographic distribution of obesity in the United States, including the association between elevation and body mass index (BMI), is largely unexplained. This study examines the relationship between obesity and elevation, ambient temperature and urbanization.Data from a cross-sectional, nationally representative sample of 422603 US adults containing BMI, behavioral (diet, physical activity, smoking) and demographic (age, sex, race/ethnicity, education, employment, income) variables from the 2011 Behavioral Risk Factor Surveillance System were merged with elevation and temperature data from WorldClim and with urbanization data from the US Department of Agriculture. There was an approximately parabolic relationship between mean annual temperature and obesity, with maximum prevalence in counties with average temperatures near 18 °C. Urbanization and obesity prevalence exhibited an inverse relationship (30.9% in rural or nonmetro counties, 29.2% in metro counties with250000 people, 28.1% in counties with population from 250000 to 1 million and 26.2% in counties with1 million). After controlling for urbanization, temperature category and behavioral and demographic factors, male and female Americans living500 m above sea level had 5.1 (95% confidence interval (CI) 2.7-9.5) and 3.9 (95% CI 1.6-9.3) times the odds of obesity, respectively, as compared with counterparts living ≥ 3000 m above sea level.Obesity prevalence in the United States is inversely associated with elevation and urbanization, after adjusting for temperature, diet, physical activity, smoking and demographic factors.

Background The association of pathogenic viruses with obesity has now been well-known in both human and animals. Globally, human obesity has become a serious problem leading to the emergence of multiple lifethreatening diseases. Adenoviruses contribute a significant role in the induction of obesity by affecting various pathways. Due to impaired immunity, obese individuals are more prone to nosocomial infections leading to complications of obesity. In contrast, several other important factors contributing to human obesity are known. Methods Currently, many published reports showed strong evidence of the role and linkage of Ad36 infection in human obesity. The Ad36 pathogenesis effect on the hepatic steatosis reduces leptin gene expression, reduced antibody response in vaccination, reduces immune system, insulin sensitivity, increases glucose uptake, activates the lipogenic and pro-inflammatory pathways in adipose tissue increases the level of Macrophage Chemo attractant Protein-1 leading chronic inflammation and affect lipid metabolism. Results The E4-ORF1 gene of Ad36 play an important role in the induction of adipogenesis and regulation of adipocyte differentiation and also known to activate the sensitizing effect of insulin. The use of E4-ORF1gene as a ligand to develop new drugs against diabetes and the prevention of Ad36 infection by an effective vaccination will attract researchers and open new area of research in the field of obesity and obesity-related multiple diseases. Conclusion Therefore, the identification and management of important contributory factors by identifying the regulation of adipocyte differentiation leading to a chronic condition like adipogenesis and insulin resistance resulting in obesity is an urgent requirement globally for human health.

In 1998, officials of the World Health Organization (WHO) declared a global epidemic of obesity, recognizing the steady rise in its prevalence in both developed and developing countries since about 1980. Obesity, defined as a body mass index (BMI in kg/m2) value of at least 30, doubled among US adults from 1980 to 2000, and tripled in children in the United States and other countries, including England, China, Thailand, and Korea. In women, the prevalence of obesity in Albania, Jordan, Panama, Paraguay, and South Africa is equal to or greater than that in the United States. Although some experts point to increased food intake, including of fast foods, and decreased activity, these factors do not explain the rise of obesity in developing countries.

Purpose The study investigated the efficacy and cost-effectiveness of a cognitive-behavioral weight management program, complemented by an interactive Web site and brief telephone/e-mail coaching. Methods In 2006–2007, 1755 overweight, non-active-duty TRICARE beneficiaries were randomized to one of three conditions with increasing intervention intensity: written materials and basic Web access (RCT1), plus an interactive Web site (RCT2), plus brief telephone/e-mail coaching support (RCT3). The study assessed changes in weight, blood pressure, and physical activity from baseline to 6, 12, and 15–18 months. (Study retention was 31% at 12 months.) Average and incremental cost-effectiveness and cost-offset analyses were conducted. Results Participants experienced significant weight loss (− 4.0%, − 4.0%, and − 5.3%, respectively, in each RCT group after 12 months and − 3.5%, − 3.8%, and − 5.1%, respectively, after 15 to 18 months), increased physical activity, and decreased blood pressure. Cost-effectiveness ratios were $900 to $1100/quality-adjusted life year (QALY) for RCT1 and RCT2 and $1900/QALY for RCT3. The cost recovery period to the government was 3 years for RCTs 1 and 2 and 6 years for RCT3. Conclusion A relatively inexpensive cognitive-behavioral weight management intervention improved patient outcomes. Extrapolation of savings for the entire TRICARE population would significantly reduce direct medical costs.

There is increasing evidence that obesity in humans is associated with infection with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36 demonstrates that this virus causes obesity. Human studies have shown a prevalence of Adv36 infection of 30% or greater in obese adult humans, but a correlation with obesity has not always been demonstrated. In contrast, three published studies and one presented study with a total of 559 children all show that there is an increase in prevalence of Adv36 infection in obese children (28%) compared to non-obese children (10%). The explanation for the apparently more robust correlation of Adv36 infection with obesity in children vs. adults is not clear. The data in animals and people suggests that Adv36 has contributed to the worldwide increase in childhood obesity. More research is needed to identify prevalences and consequences of Adv36 infection in people of all age groups and geographic locations.

Human adenovirus-36 (Ad-36) is thought to induce obesity by a direct effect of the viral E4orf1 gene on lipogenic enzymes in host adipocytes. Ad-36 prevalence is 30% in obese adults, but prevalence has not been reported in childhood obesity.To determine the prevalence of Ad-36 infection in obese Korean children (age 14.8 +/- 1.9; range 8.3-6.3 years); correlation of infection with BMI z-score and other obesity measures.Blood was drawn at the annual school physical exam or clinic visit; Ad-36 status was determined by serum neutralization assay; and routine serum chemistry values.A total of 30% of subjects were positive (N = 25) for Ad-36; 70% were negative (N = 59). Significantly higher BMI z-scores (1.92 vs. 1.65, p0.01) and waist circumferences (96.3 vs. 90.7 cm, p = 0.05) were found in infected versus uninfected children. Cardiovascular risk factors were not significantly different.Ad-36 infection is common in obese Korean children and correlates highly with obesity. Ad-36 may have played a role in the obesity and Type 2 diabetes epidemic in children.

Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice. Finally, a randomized, blinded, placebo-controlled trial in obese adult subjects was conducted. Randomization included: BUP (300 mg) + NAL (50 mg), BUP (300 mg) + placebo (P), NAL (50 mg) + P or P+P for up to 24 weeks. BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy, an effect consistent with synergism. Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment. BUP+NAL completers diverged from NAL+P (P < 0.01) and P+P (P < 0.001) at week 16 and from BUP+P by week 24 (P < 0.05). The combination was also well tolerated. Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone. These results supported the hypothesis that NAL, through blockade of β-endorphin mediated POMC autoinhibition, prevents the classic weight loss plateau observed with monotherapies such as BUP. This novel treatment approach (BUP+NAL) holds promise for the treatment of obesity.

tative bodies that it is reasonable to call obesity a disease. The panel reviewed three broad classes of argument as to whether obesity is rightly classified as a disease.The first, the scientific approach, pro-ceeds in two conceptually simple steps: i) identify the characteristics that entities must have to be considered diseases and ii) examine empirical evidence to deter-mine whether obesity possesses those characteristics. The scientific approach would be well suited to answering the question “is obesity a disease?” rather than “should we consider obesity a disease?,” were the former question answerable. However, after much deliberation, the panel concluded that the former question is ill posed and does not admit an answer. This is not because of a lack of agreement or understanding about obesity but rather because of a lack of a clear, specific, widely accepted, and scientifically applicable defi-nition of “disease” that allows one to objec-tively and empirically determine whether specific conditions are diseases.The second type of argument, the foren-sic approach, entailed looking to the public statements of authoritative bodies as evi-dence of whether obesity is a disease or should be considered a disease. A nearly of the statements made by ostensibly authoritative bodies made apparent that there is a clear and strong majority lean-ing—although not complete consensus—toward obesity being a disease. However, although some authoritative bodies have offered statements that obesity is (or is not) a disease, very few of them have published a thorough and rigorous argument or evi-dential basis in support of the statement. Moreover, and far more importantly, the panel held that the opinions of authorita-tive bodies tell us—at most—what is law-ful, consistent with mainstream opinions, or likely to be supported by others. Such opinions are insufficient to tell us what is true or what is right. The panel strongly endorsed the position that there can be no higher authority than reason. Hence, the forensic approach was judged to be inad-equate to help us determine either whether obesity is a disease or whether it should be considered a disease.The third approach to this question we termed the utilitarian approach. Recognizing that there is no clear agreed-on definition of disease with precise, assessable criteria that can be articulated, it seems that conditions that produce adverse health outcomes come to be considered diseases as the result of a social process when it is assessed to be beneficial to the greater good that they be so judged. Such judgments about likely benefit to the greater good are utilitarian judgments that may take empirical input but must also assume certain values. We considered the

The prevalence of obesity in children increased rapidly starting about 1980 in both developed and developing countries. Studies of changes in diet and physical activity, television watching, and food advertisements on television suggest that these are not sufficient to explain the epidemic. The pattern of rapid spread is suggestive of an infectious origin. The concept of virus-induced obesity is not new. Eight viruses have been shown to cause obesity in animals and there is evidence for virus-induced obesity in humans. Recent evidence on animal and human adenoviruses suggests that these adenoviruses may infect adipocytes to alter enzymes and transcription factors resulting in accumulation of triglycerides and differentiation of preadipocytes into mature adipocytes. The E4orf1 gene of Ad-36 has been shown to be responsible for the adipogenic effect. It appears that a portion of the worldwide epidemic of obesity since 1980 could be due to infections with human adenoviruses.

Summary Five human adenovirus subtypes, Ad5, Ad9, Ad31, Ad36, and Ad37, and a non-human adenovirus, SMAM1, are linked to increased adiposity in vitro or in vivo. Experimental infection with Ad5, Ad36, and Ad37 produced excess adiposity or weight gain in animals. Ad9 and Ad31 increase fat storage in tissue culture but are not associated with animal or human obesity. Ad36 is the most extensively studied adipogenic adenovirus and is correlated with some measure of overweight/obesity in humans from multiple countries. The correlation is strongest and most consistent in children, but some studies have been negative in both children and adults. About 30% of overweight/obese children and adults and about 15–20% of lean individuals have Ad36 antibodies in epidemiologic studies. The mechanisms of action of Ad36 are due to the early gene 4, open reading frame 1 (E4-ORF1). Blocking E4-ORF1 with siRNA prevents the effects of Ad36, and transfection of lentivirus with E4-ORF1 reproduces the Ad36 effects. Increased adiposity is caused by stimulation of at least three pathways by Ad36. Cell membrane glucose receptors are increased via the Ras pathway, leading to increased intracellular glucose. Fatty acid synthase is increased, which converts the glucose to fatty acids. Finally, peroxisome proliferator-activated receptor-γ is increased, resulting in differentiation of adult stem cells into adipocytes. Conclusions: several adenoviruses increase adiposity in animals and are associated with obesity in humans. There are critical gaps in the literature needing further investigation including evaluation of other adenovirus subtypes and better research designs to improve the strength of causal inferences. Copyright © 2015 John Wiley & Sons, Ltd.

Human adenovirus-36 (Ad-36) increases adiposity and paradoxically lowers serum cholesterol and triglycerides in chickens, mice, and non-human primates. The role of Ad-36 in human obesity is unknown. To determine the prevalence of Ad-36 antibodies in obese and nonobese humans. To evaluate the association of Ad-36 antibodies with body mass index (BMI) and serum lipids. Cohort study. Volunteers from obesity treatment programs, communities, and a research study. Obese and nonobese volunteers at the University of Wisconsin, Madison, WI, and the Bowen Center, Naples, Florida. Obese and thin volunteer research subjects and 89 twin pairs at Columbia University, New York. Study 1: 502 subjects; serum neutralization assay for antibodies to Ad-2, Ad-31, Ad-36, and Ad-37; serum cholesterol and triglycerides assays. Study 2: BMI and %body fat in 28 twin pairs discordant for Ad-36 antibodies. Presence of antibodies to adenoviruses, BMI, serum cholesterol and triglycerides levels. Significant (P

We have previously reported that prior exercise increases the oxidation of dietary monounsaturated fat in comparison to rest when the fat is given in a mixed meal 30 min following the completion of exercise. In this study, we determined whether the increase in dietary fat oxidation after exercise persisted when the time between exercise and fatty acid administration was lengthened.Six female subjects (age=24+/-0.1 y, BMI=21+/-1 kg/m2) were recruited for a total of six visits each. During three visits, a stationary cycle exercise session (1250 kJ) was performed at 65% VO2 peak in a whole-body calorimeter; while during three other visits, exercise was replaced with rest. Subjects received [1-13C]oleate and [d31]palmitate with a different meal at each visit: breakfast, lunch, and dinner.Dietary oleate oxidation following prior rest did not differ between dose times and was 36+/-3, 42+/-5, and 42+/-3% for the 13 h following breakfast, lunch, and dinner. Prior exercise resulted in greater oleate oxidation following all dose times than prior rest (P0.01) being 52+/-4, 64+/-3, and 53+/-3% for the breakfast, lunch, and dinner dose. The oxidation was significantly greater following lunch than the other dose times (P0.05). Prior exercise (1250 kJ) did not result in greater oxidation of palmitate; however, oxidation following prior exercise increased with later dose times (13+/-2, 23+/-2, and 23+/-3% for breakfast, lunch, and dinner; P0.05) and following rest (18+/-2, 22+/-2, and 27+/-2% for breakfast, lunch, and dinner; P0.005).The increase in oleate oxidation when administered after early morning exercise was found to persist for all three meals of the day, with the greatest effect occurring for the lunch meal. Palmitate oxidation, while apparently resistant to the effects of 1250 kJ of prior exercise, increases when administered later in the day, suggesting a diurnal variation in the oxidation of dietary fatty acids. These results demonstrate that prior exercise selectively alters the partitioning of dietary fatty acids. Furthermore, these findings demonstrate additional benefits of substituting monounsaturated for saturated fatty acids in the diet.

Conjugated linoleic acid (CLA) is marketed in numerous commercially available dietary supplements, but few studies have looked at the long-term safety of this product. The current study evaluated the safety of one CLA product (Clarinol) over a one-year period in obese humans who were generally healthy. This was a randomized, double-blind study consisting of three phases in which subjects were given 6 g/day of CLA or placebo. Phase 1 was a low calorie diet (13 kcal/kg desirable weight) for 12 weeks or until 10-20% of initial body weight was lost. In phase 2, from weeks 12 to 28, subjects were re-fed a diet providing 25-30 kcal/kg of desirable body weight. Phase 3 was open label, with subjects from both groups taking CLA from weeks 28 to 52. At biweekly visits, subjects completed a questionnaire evaluating side effects and adverse events. Blood was taken for assay of liver function, glucose, insulin, serum lipids, blood counts, and general chemistry. Overall, body composition did not differ between groups. Laboratory tests showed no adverse effects of CLA. Adverse events and side effects were less in the CLA group compared to placebo. We conclude that CLA as Clarinol is safe for use in obese humans for at least one year.

Objectives: Adenovirus 36 (Ad-36) has been shown to increase adiposity in experimentally infected chickens, mice, and marmosets (nonhuman primates). Neutralizing antibodies to Ad-36 are associated with obesity in humans. The metabolic and molecular mechanisms responsible for Ad-36-induced adipogenesis are unknown. As a potential adipogenic mechanism, this study examined if Ad-36 enhanced differentiation of preadipocytes. Research Methods and Procedures: To determine the suitability of 3T3-L1 cells (murine preadipocyte cell line) as a model, the first experiment determined if Ad-36 attaches and initiates replication in the cells. Next, effects of Ad-36 on the number of differentiated adipocytes, glycerol 3-phosphate dehydrogenase (GPDH) levels, and cellular lipid accumulation were determined. The last experiment determined the effect of Ad-36 on human primary preadipocyte differentiation. Ad-2, a known nonadipogenic human adenovirus, was used as a negative control in these experiments. Results: Immunofluorescence studies showed adenoviral attachment to 3T3-L1 cells, and reverse transcriptase-polymerase chain reaction showed expression of the Ad-36 E1A gene in the infected cells. Ad-36, but not Ad-2, increased the number of differentiated adipocytes, GPDH enzyme levels, and the total cellular lipid content. Also, Ad-36, but not Ad-2, increased GPDH levels in human preadipocytes. Discussion: Taken together, these experiments showed that Ad-36 enhanced differentiation of preadipocytes, which may be a contributory mechanism to its adipogenic effect in vivo. The lack of effect of Ad-2 on differentiation demonstrated that the observed findings were not a common characteristic of all adenoviruses. Future understanding of the molecular interactions of cellular and viral genes responsible for enhanced differentiation may reveal novel signaling pathways and controls of preadipocyte differentiation.

The potential of bioelectrical impedance spectroscopy (BIS) for assessing nutritional status in spaceflight was tested in two head-down-tilt bed-rest studies. BIS-predicted extracellular water (ECW), intracellular water (ICW), and total body water (TBW) measured using knee-elbow electrode placement were compared with deuterium and bromide dilution (DIL) volumes in healthy, 19- to 45-yr-old subjects. BIS was accurate during 44 h of head-down tilt with mean differences (BIS - DIL) of 0–0.1 kg for ECW, 0.3–0.5 for ICW, and 0.4–0.6 kg for TBW ( n = 28). At 44 h, BIS followed the within-individual change in body water compartments with a relative prediction error (standard error of the estimate/baseline volume) of 2.0–3.6% of water space. In the second study, BIS did not detect an acute decrease (-1.41 ± 0.91 kg) in ICW secondary to 48 h of a protein-free, 800 kcal/day diet ( n = 18). BIS's insensitivity to ICW losses may be because they were predominantly (65%) localized to the trunk and/or because there was a general failure of BIS to measure ICW independently of ECW and TBW. BIS may have potential for measuring nutritional status during spaceflight, but its limitations in precision and insensitivity to acute ICW changes warrant further validation studies.

Although obesity has multiple etiologies, an overlooked possibility is an infectious origin. We previously identified two viruses, SMAM-1, an avian adenovirus (Ad), and Ad-36, a human adenovirus, that produce a syndrome of visceral obesity, with paradoxically decreased serum cholesterol and triglycerides in chickens and mice. In the two studies presented in this paper, we used nonhuman primates to investigate the adiposity-promoting potential of Ad-36. In study 1, we observed spontaneously occurring Ad-36 antibodies in 15 male rhesus monkeys, and a significant longitudinal association of positive antibody status with weight gain and plasma cholesterol lowering during the 18 mo after viral antibody appearance. In study 2, which was a randomized controlled experiment, three male marmosets inoculated with Ad-36 had a threefold body weight gain, a greater fat gain and lower serum cholesterol relative to baseline (P

Editors’ note: Omitting obesity treatment leads to poor outcomes, even in those who appear to be metabolically healthy

Obesity is a public health priority, which also threatens national security. Adenovirus 36 (Adv36) increases adiposity in animals and Adv36 antibody status is associated with human obesity, but it is unknown whether infection predicts the development of human adiposity.The objective of the study was to assess infection status and subsequent weight gain.The study had a retrospective cohort design.The study was conducted at Air Force fitness testing and clinical encounters.PARTICIPANTS included Air Force male enlistees, aged 18-22 years, with a baseline body mass index (BMI) of 20-30 kg/m(2) followed up from enlistment (beginning in 1995) until 2012 or separation from the Air Force.EXPOSURE included Adv36 infection status at the time of entry.Follow-up BMI, the primary outcome, and diagnosis of overweight/obesity by the International Classification of Diseases, ninth revision V85.25+ and 278.0* series (secondary outcome) were recorded.The last recorded follow-up BMI was similar among infected and uninfected, 26.4 and 27.2 kg/m(2), respectively (P.05). However, infected individuals had a higher hazard of a medical provider's diagnosis of overweight/obese over time (hazard ratio 1.8, 95% confidence interval 1.0-3.1, P = .04), adjusted for baseline BMI. Additionally, infected individuals who were lean at baseline (BMI of 22.5 kg/m(2)) had a 3.9 times greater hazard of developing an overweight/obese clinical diagnosis (95% confidence interval 1.5-9.7, P = .004) compared with uninfected lean individuals after adjusting for interaction (P = .03) between infection and baseline BMI.The presence of Adv36 antibodies was not associated with higher BMI at baseline or follow-up within this military population. However, being infected was associated with developing a clinical diagnosis of overweight/obesity, especially among those lean at baseline.

Obesity is a new specialty of medicine fighting for recognition. Current treatments with diet, exercise, and lifestyle modification have a high failure rate. Few obesity drugs exist and they are not very effective. Research should focus on understanding basic mechanisms, the numerous etiologies of obesity, and new drug development. Understanding the mechanisms of bariatric surgery, which does work, will lead to new drugs and better treatment.

As part of an effort to review current understanding of the mechanisms by which caloric restriction (CR) extends maximum life span, the authors of the present review were requested to develop a list of key issues concerning the potential role of neuroendocrine systems in mediating these effects. It has long been hypothesized that failure of specific neuroendocrine functions during aging leads to key age-related systemic and physiological failures, and more recently it has been postulated that physiological neuroendocrine responses to CR may increase life span. However, although the acute neuroendocrine responses to fasting have been well studied, it is not clear that these responses are necessarily identical to those observed in response to the chronic moderate (30% to 50% reduction) CR that increases maximum life span. Therefore the recommendations of this panel fall into two categories. First, further characterization of neuroendocrine responses to CR over the entire life span is needed. Second, rigorous interventional studies are needed to test the extent to which neuroendocrine responses to CR mediate the effects of CR on life span, or alternatively if CR protects the function of essential neuroendocrine cells whose impairment reduces life span. Complementary studies using rodent models, nonhuman primates, and humans will be essential to assess the generality of elucidated mechanisms, and to determine if such mechanisms might apply to humans.

Massive adipose tissue depositions in the abdomen and thorax sufficient to interfere with respiration developed in a patient with multiple medical problems. Biopsy of adipose tissue identified human adenovirus 36 (Adv 36) DNA. Adv 36 causes adipogenesis in animals and humans. Development of massive lipomatosis may be caused by Adv 36.

Conjugated linoleic acid (CLA) is being sold as a panacea that has the capability of reducing or eliminating cancer, preventing heart disease, improving immune function, and altering body composition to treat obesity or build lean body mass. Unfortunately, there has been very little published human research on CLA. This review will examine the literature on CLA and discuss the animal research on which the above claims are made. The limited human studies will be presented with an evaluation of the potential uses of CLA for human health and disease.

BACKGROUND: Four animal models of virus-induced obesity including adiposity induced by an avian adenovirus have been described previously. This is the first report of adiposity induced in animals by a human virus. OBJECTIVE: We investigated the adiposity promoting effect of a human adenovirus (Ad-36) in two different animal models. DESIGN: Due to the novel nature of the findings we replicated the experiments using a chicken model three times and a mammal model once. In four separate experiments, chickens and mice were inoculated with human adenovirus Ad-36. Weight matched groups inoculated with tissue culture media were used as non-infected controls in each experiment. Ad-36 inoculated and uninfected control groups were housed in separate rooms under biosafety level 2 or better containment. The first experiment included an additional weight matched group of chickens that was inoculated with CELO (chick embryo lethal orphan virus), an avian adenovirus. Food intakes and body weights were measured weekly. At the time of sacrifice blood was drawn and visceral fat was carefully separated and weighed. Total body fat was determined by chemical extraction of carcass fat. RESULTS: Animals inoculated with Ad-36 developed a syndrome of increased adipose tissue and paradoxically low levels of serum cholesterol and triglycerides. This syndrome was not seen in chickens inoculated with CELO virus. Sections of the brain and hypothalamus of Ad-36 inoculated animals did not show any overt histopathological changes. Ad-36 DNA could be detected in adipose tissue, but not skeletal muscles of randomly selected animals for as long as 16 weeks after Ad-36 inoculation. CONCLUSIONS: Data from these animal models suggest that the role of viral disease in the etiology of human obesity must be considered.

An adenovirus, AD-36, has been linked to human adiposity and a sensitive and reliable quantitative method is required to assess AD-36 viral loads. This report describes direct detection of AD-36 viral DNA, which is the first method to quantitate DNA without amplification. Total genomic DNA is hybridized with an AD-36 specific fluorescently labeled probe and analyzed by capillary electrophoresis with laser-induced fluorescence. The minimum detectable quantity is 10.3 ng/ml, corresponding to 282 copies of AD-36 with a precision of 1-6%. These results indicate that direct detection with capillary electrophoresis with laser-induced fluorescence (CE-LIF) is a reliable and sensitive method for quantifying AD-36 viral DNA.

BACKGROUND: Initial weight loss has been used as a predictor of long-term response to obesity drugs. Discontinuation of drugs has been recommended if weight loss is not ≥1.81 kg (4 lb) in the first month of treatment. OBJECTIVE: We compared the weight loss response at 6 months of patients losing ≥1.81 kg (responders) vs

Lonergan, Robert P., III, J. Catsby Ware, Richard L. Atkinson, W. Christopher Winter, and Paul M. Suratt. Sleep apnea in obese miniature pigs. J. Appl. Physiol. 84(2): 531–536, 1998.—We postulated that three extremely obese Yucatan miniature pigs would have more sleep apnea than three nonobese Yucatan miniature pigs. Pigs were studied with the use of electroencephalograms, inductance plethysmography, oximetry, expired nasal CO2, or thermistors. All of the obese pigs, but none of the nonobese pigs, had both sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. 0 apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 ± 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigs vs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleep apnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggest that this animal can be used as a model for sleep apnea in obesity.

To determine the safety, efficacy, and metabolic changes in patients with morbid obesity treated with d,l-fenfluramine and phentermine in an open-label trial.In patients with a body mass index (BMI) =40.0 kg/m 2 (N = 298) who sought assistance at a private medical practice for treatment of obesity, 60 mg of d,l-fenfluramine and 15 to 30 mg of phentermine resin were administered daily in an open-label trial, without placebo controls, for up to 24 months. The setting was a community-based private practice. Study subjects were given instructions for a 1,200 to 1,400 kcal/day diet, exercise, and behavior modification. Follow-up included a monthly medical visit, behavior modification group attendance, quarterly laboratory evaluation, and electrocardiographic monitoring.BMI decreased from 45.8 kg/m2 to 37.4 kg/m2 (P0.0001) in those who completed 12 months of treatment and to 38.2 kg/m2 (P0.0001) in those who continued the protocol for 24 months. Statistically significant decreases in fasting blood glucose, total and high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressures, and fasting insulin concentrations were noted. The dropout rate was 42.3% at 12 months and 69.8% at 24 months. The most common reason given for discontinuing participation in the study was "success" with the program (mean BMI loss of 7.8 kg/m2). Five patients discontinued treatment because of side effects. No laboratory or electrocardiographic abnormalities were noted that could be attributed to the medications. No statistically significant regain of weight occurred in those who completed 12 or 24 months of treatment.In this study, treatment of morbid obesity with d,l-fenfluramine and phentermine was safe and efficacious in promoting and maintaining weight loss. Moreover, statistically significant changes were noted in metabolic variables associated with risk of heart disease. Future efforts must focus on methods to improve long-term compliance.

Previous studies have shown that tumor necrosis factor (TNF)-α production from adipose tissue is elevated in rodent and human obesity and plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and protein levels were similar in these subjects. TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-α mRNA expression in fat tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-α.

The etiology of obesity is generally attributed to a lack of willpower on the part of obese people plus a contribution from epigenetic and genetic factors. This chapter postulates that a major portion of the worldwide epidemic of obesity since 1980 is due to infection with human adenovirus 36 (Adv36). Adv36 causes obesity in multiple animal species and is strongly associated with obesity in humans. The prevalence of Adv36 infection averages about 30 % in obese adults and children and about 18 % in nonobese individuals. Adv36 infection correlates with body weight or body fat, especially in children. The mechanisms of Adv36-induced obesity are alteration of multiple molecular and biochemical pathways by the E4orf1 gene of Adv36. The main alterations are an increase of glucose transport into cells and increased production of fatty acids from the glucose under the influence of fatty acid synthase. An infectious cause of obesity demands changes in governmental and insurance company policies that heretofore have not considered obesity a disease. The production of a vaccine against Adv36 holds promise to lower the prevalence of obesity and result in improved health and large economic savings across the world.