[EXCESS WEIGHT AND SOCIODEMOGRAPHIC RISK FACTORS FOR SARS-COV-2 INFECTION IN ISRAEL].

BACKGROUND: Studies to date have demonstrated an increased prevalence of obesity and low socioeconomic status (SES( among people with confirmed cases of COVID-19, and low SES has been linked to obesity. OBJECTIVES: Our goal was to better understand the important relationship between body weight and sociodemographic variables affecting the COVID-19 burden. METHODS: We conducted a cross-sectional study of subjects presenting to Israel's largest emergency department and their odds for positive SARS-CoV-2 virus PCR testing during the first wave of the pandemic. RESULTS: We found that as BMI rises, as compared to normal weight, it is associated with increasing odds for testing positive, independently of age, gender, SES and population density (BMI 25-29.9 kg/m2: OR = 1.42, 95% CI 1.07 - 1.90; BMI 30-34.9 kg/m2: OR = 1.50, 95% CI 1.06 - 2.11; BMI ≥ 35 kg/m2: OR = 1.61, 95% CI 1.02 - 2.46). Furthermore, male gender, low SES and high population density are also associated with excess risk for positive test results independently of body weight. CONCLUSIONS: Understanding these risk factors for infection and how they might interplay can help the medical community develop approaches to protect at-risk groups from infection and severe disease secondary to seasonal and pandemic viral infections.

Humoral Immunity of Unvaccinated COVID-19 Recovered vs. Naïve BNT162b2 Vaccinated Individuals: A Prospective Longitudinal Study.

To study the differences in the immune response to SARS-CoV-2 infection compared to the response to vaccination, we characterized the humoral immune kinetics of these situations. In this prospective longitudinal study, we followed unvaccinated COVID-19-recovered individuals (n = 130) and naïve, two-dose BNT162b2-vaccinated individuals (n = 372) who were age- and BMI-matched for six months during the first pandemic year. Anti-RBD-IgG, neutralizing antibodies (NAbs), and avidity were assessed monthly. For recovered patients, data on symptoms and the severity of the disease were collected. Anti-RBD-IgG and NAbs titers at peak were higher after vaccination vs. after infection, but the decline was steeper (peak log IgG: 3.08 vs. 1.81, peak log NAbs: 5.93 vs. 5.04, slopes: -0.54 vs. -0.26). Peak anti-RBD-IgG and NAbs were higher in recovered individuals with BMI > 30 and in older individuals compared to individuals with BMI < 30, younger population. Of the recovered, 42 (36%) experienced long-COVID symptoms. Avidity was initially higher in vaccinated individuals compared with recovered individuals, though with time, it increased in recovered individuals but not among vaccinated individuals. Here, we show that while the initial antibody titers, neutralization, and avidity are lower in SARS-CoV-2-recovered individuals, they persist for a longer duration. These results suggest differential protection against COVID-19 in recovered-unvaccinated vs. naïve-vaccinated individuals.

Managing Obesity in Lockdown: Survey of Health Behaviors and Telemedicine.

Since the outbreak of COVID-19, billions of people have gone into lockdown, facing pandemic related challenges that engender weight gain, especially in the obese. We report the results of an online survey, conducted during Israel's first quarantine, of 279 adults treated in hospital-based obesity clinics with counseling, medications, surgery, endoscopic procedures, or any combination of these for weight loss. In this study, we assessed the association between changes in dietary and lifestyle habits and body weight, and the benefits of receiving weight management care remotely through telemedicine during lockdown. Compared to patients not receiving obesity care via telemedicine, patients receiving this care were more likely to lose weight (OR, 2.79; p = 0.042) and also to increase participation in exercise (OR, 2.4; p = 0.022). While 40% of respondents reported consuming more sweet or salty processed snacks and 33% reported less vegetables and fruits, 65% reported more homemade foods. At the same time, 40% of respondents reported a reduction in exercise and 52% reported a decline in mood. Alterations in these eating patterns, as well as in exercise habits and mood, were significantly associated with weight changes. This study highlights that lockdown affects health behaviors associated with weight change, and advocates for the use of telemedicine to provide ongoing obesity care during future quarantines in order to promote weight loss and prevent weight gain.

ACTION-IO as a platform to understand differences in perceptions, attitudes, and behaviors of people with obesity and physicians across countries - the Israeli experience.

BACKGROUND: Obesity is a highly prevalent, complex, and chronic relapsing disease with a considerable unmet medical need. We aimed to identify perceptions, attitudes, behaviors, and barriers to effective obesity treatment among people with obesity (PwO) and physicians in Israel. METHODS: The ACTION-IO study was an online survey conducted in 11 countries, including Israel. Findings from the Israeli cohort are reported here. Israeli respondents were PwO (body mass index of ≥30 kg/m2 based on self-reported height and weight) and physicians primarily in direct patient care. RESULTS: In total, 750 PwO and 169 physicians completed the survey in Israel. Although most PwO (70%) and physicians (95%) perceived obesity as a chronic disease, the majority of PwO assumed full responsibility for their own weight loss (88%) compared with only 19% of physicians who placed the responsibility for weight loss on their patients with obesity. Many PwO (62%) and physicians (73%) agreed that a complete change in lifestyle would be required for PwO to lose weight and felt that treatment of obesity should be a team effort between different healthcare professionals (HCPs; 80 and 90%, respectively). Dietitians were considered by 82% of physicians to be the most effective professionals in helping PwO achieve their weight loss goals. Many PwO (69%) liked that their HCP initiated weight management discussions and 68% of those who had not previously discussed their weight would like their HCP to initiate the conversation. However, among PwO who had discussed their weight with an HCP, 59% considered the discussions to be a little helpful or not at all helpful. The beliefs that patients have little interest in or motivation for losing weight were identified by physicians as the main reasons (71 and 70%, respectively) for not initiating weight management discussions. CONCLUSIONS: In line with the ACTION-IO international study, our Israeli dataset reveals a need to improve awareness, primarily among physicians, on the physiologic basis and clinical management of obesity, including how to approach weight and weight management discussions during patient consultations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov , NCT03584191 . Data first posted on ClinicalTrials.gov : 12 July 2018 - 'Retrospectively registered'.

[Obesity, bariatric surgery and future fertility].

Obesity is an increasingly widespread health problem. In addition to comorbidities such as diabetes, hypertension, dyslipidemia and cardiovascular disease, obesity has a significant impact on reproductive life, including infertility, miscarriages and high prevalence of pregnancy complications. The present review describes the possible benefits of bariatric surgery regarding fertility and pregnancy outcome. It is well established that bariatric surgery leads to regular ovulatory cycles and improves spontaneous conception rates in obese women. While pregnancy after bariatric surgery is safe and associated with reduced pregnancy complications, pregnant women following bariatric surgery are still at high risk for preterm births and small dimensions of gestational age offsprings. The optimal interval that should be kept between surgery and subsequent pregnancy is controversial, with recent studies emphasizing the importance of nutritional balance rather than the time from surgery to conception as being the most important determinant. Strict peri-conceptional surveillance is mandatory in order to prevent nutritional deficiencies and for the early diagnosis of abnormal fetal growth.

Animal models in obesity and hypertension.

Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.

Ablation of the hypothalamic neuropeptide melanin concentrating hormone is associated with behavioral abnormalities that reflect impaired olfactory integration.

Melanin-concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide. At least one receptor, MCH receptor 1 (MCHR1), is present in all mammals and is expressed widely throughout the brain, including cortex, striatum and structures implicated in the integration of olfactory cues such as the piriform cortex and olfactory bulb. Consistent with a potential role for MCH in mediating olfactory function, MCH knockout mice demonstrate abnormal olfactory behaviors. These behaviors include impaired food seeking by both genders in the context of normal levels of exploratory behavior, suggesting impaired olfaction. Males also exhibit increased aggression while females show defects in several olfactory mediated behaviors including mating, estrous cycle synchronization and maternal behavior. These findings suggest that hypothalamic inputs through MCH play an important role in regulating sensory integration from olfactory pathways.

Laparoscopic sleeve gastrectomy as a revisional option after gastric band failure.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is an effective bariatric procedure with low morbidity and mortality. Unfortunately, it is fraught with high failure rates in long-term follow-up. Laparoscopic sleeve gastrectomy (LSG) is an emerging procedure, quickly gaining momentum in the arsenal of bariatric practice as a first step toward gastric bypass/biliopancreatic diversion or as a stand-alone operation. Recently, it has been described as a revisional option for previous bariatric surgery failures. We report our early experience with LSG as a revisional procedure for failed LAGB. METHODS: From January 2007 to April 2010, 46 patients, who had undergone LAGB, underwent LSG. Patient demographics, reason for band removal, interval between removal and LSG, operative times, estimated blood loss, complications, length of hospital stay, and percent of excess weight loss were collected. RESULTS: Of the 46 patients, 20 (43%) had their bands removed before LSG (median time interval, 2 years; range, 2 months to 9 years); the rest had concomitant band removal and LSG. Twelve patients were men (26%). Mean age and BMI were 40 (range, 20-60) years and 43.1 kg/m(2) (range, 33-57), respectively. In two cases, surgery was converted to an open procedure due to extensive adhesions related to previous surgeries. Median operative time, estimated blood loss, and length of hospital stay were 118 (range, 70-250) minutes, 41 (range, 5-600) ml, and 3 (range, 1-100) days, respectively. Major morbidity was encountered in three patients (6%; leak in 2 and bleeding in 1). There were no mortalities. Mean follow-up time for our cohort is 17 (range, 1-39) months. Percent of excess weight loss at 2, 6, 12, 24, and 36 months was 24, 37, 53, 51, and 48%, respectively. CONCLUSIONS: Our results suggest that LSG is safe, feasible, and effective as a revisional procedure for failed LAGB and can be considered as an appealing option in these cases. Larger series and longer follow-up are needed to confirm this.

Chronic MCH infusion causes a decrease in energy expenditure and body temperature, and an increase in serum IGF-1 levels in mice.

Melanin concentrating hormone (MCH) is an orexigenic peptide secreted from the lateral hypothalamus. Various observations suggest a role for MCH in energy expenditure in transgenic mice; however, the influence of MCH on energy expenditure and body temperature in WT mice was inadequately studied. Therefore, our first goal was to characterize the influence of chronic intracerebroventrical MCH infusion on energy homeostasis in mice. Our second goal was to explore the effect of MCH on the GH-insulin like growth factor 1 (IGF-1) axis in vivo. We have recently published that MCH directly increased GH-secretion from pituitary cells in vitro, suggesting that MCH may exert part of its effects on energy balance via direct pituitary hormone regulation. Mice were centrally infused with MCH for 14 days, resulting in a significant increase in food intake, body weight, fat mass and plasma IGF-1 levels, while decreasing body temperature and energy expenditure. Our data emphasize the role of MCH as a key regulator of energy homeostasis by means of appetite regulation, regulation of energy expenditure, and an integrator of energy balance with the neuroendocrine system regulating pituitary hormone secretion. They also support the notion that MCH may have a physiologic role in GH regulation that may, in turn, contribute to its effect on body weight.

Melanin-concentrating hormone stimulates human growth hormone secretion: a novel effect of MCH on the hypothalamic-pituitary axis.

Melanin-concentrating hormone (MCH), a 19-amino acid orexigenic (appetite-stimulating) hypothalamic peptide, is an important regulator of energy homeostasis. It is cleaved from its precursor prepro-MCH (ppMCH) along with several other neuropeptides whose roles are not fully defined. Because pituitary hormones such as growth hormone (GH), ACTH, and thyroid-stimulating hormone affect body weight and composition, appetite, insulin sensitivity, and lipoprotein metabolism, we investigated whether MCH exerts direct effects on the human pituitary to regulate energy balance using dispersed human fetal pituitaries (21-22 wk gestation) and cultured GH-secreting adenomas. We found that MCH receptor-1 (MCH-R1), but not MCH receptor-2, is expressed in both normal (fetal and adult) human pituitary tissues and in GH cell adenomas. MCH (10 nM) stimulated GH release from human fetal pituitary cultures by up to 62% during a 4-h incubation (P < 0.05). Interestingly, neuropeptide EI (10 nM), which is also cleaved from ppMCH, increased human GH secretion by up to 124% in fetal pituitaries. A milder, albeit significant, induction of GH secretion by MCH (20%) was seen in cultured GH-secreting pituitary adenomas. A comparable stimulation of GH secretion was seen when cultured mouse pituitary cells were treated with MCH. Treatment of cultured GH adenoma cells with MCH (100 nM) induced extracellular signal-regulated kinases 1 and 2 phosphorylation, suggesting activation of MCH-R1. In aggregate, these data suggest that MCH may regulate pituitary GH secretion and imply a potential cross-talk mechanism between appetite-regulating neuropeptides and pituitary hormones.

Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone.

OBJECTIVE: Treatment of male rodents with estradiol (E2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin-concentrating hormone (MCH) and the appetite-inhibiting, fat-derived hormone leptin in mediating E2-induced anorexia. RESEARCH METHODS AND PROCEDURES: We studied the effect of E2 treatment (implantation of either E2 pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin-deficient ob/ob mice). We also studied the effect of E2 treatment in the context of high-fat diet. RESULTS: We confirmed E2 dose-dependent anorexia in male wild type mice fed a normal chow diet. E2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E2-implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E2-induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2-induced anorexia. E2-implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E2-induced anorexia. High-fat diet significantly exacerbated the effect of E2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week. DISCUSSION: The anorectic effects of E2 were independent of MCH and leptin. Our results suggested that E2 may have effects on nutrient preferences.

Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype.

Energy homeostasis is regulated by a complex network involving peripheral and central signals that determine food intake and energy expenditure. Melanin-concentrating hormone (MCH) plays an essential role in this process. Animals treated with MCH develop hyperphagia and obesity. Ablation of the prepro-MCH gene leads to a lean phenotype, as does ablation of the rodent MCH receptor, MCHR-1. MCH is overexpressed in the leptin-deficient ob/ob mouse, and we hypothesized that ablation of MCH in this animal would lead to attenuation of its obese phenotype. Compared with ob/ob animals, mice lacking both leptin and MCH (double null) had a dramatic reduction in body fat. Surprisingly, the hyperphagia of the ob/ob mouse was unaffected. Instead, leanness was secondary to a marked increase in energy expenditure resulting from both increased resting energy expenditure and locomotor activity. Furthermore, double-null mice showed improvements in other parameters impaired in ob/ob mice. Compared with ob/ob mice, double-null animals had increased basal body temperature, improved response to cold exposure, lower plasma glucocorticoid levels, improved glucose tolerance, and reduced expression of stearoyl-CoA desaturase 1 (SCD-1). These results highlight the importance of MCH in integration of energy homeostasis downstream of leptin and, in particular, the role of MCH in regulation of energy expenditure.

NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting.

Neuropeptide Y (NPY) is an orexigenic (appetite-stimulating) peptide that plays an important role in regulating energy balance. When administered directly into the central nervous system, animals exhibit an immediate increase in feeding behavior, and repetitive injections or chronic infusions lead to obesity. Surprisingly, initial studies of Npy(-/-) mice on a mixed genetic background did not reveal deficits in energy balance, with the exception of an attenuation in obesity seen in ob/ob mice in which the NPY gene was also deleted. Here, we show that, on a C57BL/6 background, NPY ablation is associated with an increase in body weight and adiposity and a significant defect in refeeding after a fast. This impaired refeeding response in Npy(-/-) mice resulted in a deficit in weight gain in these animals after 24 h of refeeding. These data indicate that genetic background must be taken into account when the biological role of NPY is evaluated. When examined on a C57BL/6 background, NPY is important for the normal refeeding response after starvation, and its absence promotes mild obesity.