Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling.

In the hypothalamic arcuate nucleus (ARC), proopiomelanocortin (POMC) neurons and the POMC-derived peptide α-melanocyte-stimulating hormone (α-MSH) promote satiety. POMC neurons receive orexin-A (OX-A)-expressing inputs and express both OX-A receptor type 1 (OX-1R) and cannabinoid receptor type 1 (CB1R) on the plasma membrane. OX-A is crucial for the control of wakefulness and energy homeostasis and promotes, in OX-1R-expressing cells, the biosynthesis of the endogenous counterpart of marijuana's psychotropic and appetite-inducing component Δ(9)-tetrahydrocannabinol, i.e., the endocannabinoid 2-arachidonoylglycerol (2-AG), which acts at CB1R. We report that OX-A/OX-1R signaling at POMC neurons promotes 2-AG biosynthesis, hyperphagia, and weight gain by blunting α-MSH production via CB1R-induced and extracellular-signal-regulated kinase 1/2 activation- and STAT3 inhibition-mediated suppression of Pomc gene transcription. Because the systemic pharmacological blockade of OX-1R by SB334867 caused anorectic effects by reducing food intake and body weight, our results unravel a previously unsuspected role for OX-A in endocannabinoid-mediated promotion of appetite by combining OX-induced alertness with food seeking. Notably, increased OX-A trafficking was found in the fibers projecting to the ARC of obese mice (ob/ob and high-fat diet fed) concurrently with elevation of OX-A release in the cerebrospinal fluid and blood of mice. Furthermore, a negative correlation between OX-A and α-MSH serum levels was found in obese mice as well as in human obese subjects (body mass index > 40), in combination with elevation of alanine aminotransferase and γ-glutamyl transferase, two markers of fatty liver disease. These alterations were counteracted by antagonism of OX-1R, thus providing the basis for a therapeutic treatment of these diseases.

Serum levels of Lp(a) are related to waist circumference in NAFLD patients with low prevalence of co-morbidities.

BACKGROUND: Novel evidence suggests a relationship between circulating Lp(a) levels and the presence of cardiovascular events independently from the cardio-metabolic profile. METHODS AND RESULTS: The purpose of this study was to investigate serum Lp(a) concentrations in relation to carotid intima-media thickness (IMT), anthropometric measures, lipid profile, assessment of insulin resistance, and other parameters conventionally used to predict CVD risk, in obese patients suffering from hepatic steatosis (HS), the well-known nonalcoholic fatty liver disease (NAFLD). Evidencing the key-points of this research, firstly, serum Lp(a) concentrations were not associated with carotid IMT in this selected population or, consequently, with early atherosclerosis, at least as evaluated by IMT. Secondly, carotid IMT was not predicted by HS severity, as evaluated by ultrasound. Finally, in the adjusted model, Lp(a) was positively predicted by waist circumference (WC) (ß = 0.25, t = 2.3, p = 0.02) and negatively by central adiposity, assessed as visceral adipose tissue at US (ß = -0.33, t = -3.0, p = 0.003). CONCLUSION: Serum Lp(a) values may not play a direct role in increasing IMT, albeit associated with WC.

Bisphenol-A plasma levels are related to inflammatory markers, visceral obesity and insulin-resistance: a cross-sectional study on adult male population.

BACKGROUND: The current increase of obesity and metabolic syndrome (MS) focuses attention on bisphenol-A (BPA), "obesogen" endocrine disruptor, main plastic component. Aim was to verify the role of BPA in metabolic alterations, insulin resistance, low grade inflammation and visceral obesity. METHODS: A cross-sectional study was performed in 76 out of 139 environmentally exposed adult males, unselected Caucasian subjects, enrolled by routine health survey at the "Federico II" University of Naples outpatient facilities. BPA plasma levels (ELISA), metabolic risk factors, homeostasis model assessment of insulin resistance index, plasma monocyte chemoattractant protein 1, interleukin-6 (IL-6) and tumor necrosis factor-alpha were performed. Clinical and biochemical parameters have been compared with BPA and pro-inflammatory cytokines levels. RESULTS: In total 24 subjects out of 76 (32%) presented with waist circumference (WC) >102 cm, 36 (47%) had impaired fasting glucose and 24 (32%) subjects had insulin resistance [11 out 52 (21%) with WC ≤102 cm and 13 out of 24 with WC >102 cm (54%), χ(2) 6.825, p = 0.009]. BPA and pro-inflammatory cytokine levels were significantly higher in subjects with visceral adiposity (WC > 102 cm). BPA correlated with WC, triglycerides, glucose homeostasis and inflammatory markers. At the multivariate analysis WC and IL-6 remained the main predictors of BPA. CONCLUSIONS: Detectable BPA plasma levels have been found also in our population. The strictly association between BPA and WC, components of MS, and inflammatory markers, further supports the BPA role in visceral obesity-related low grade chronic inflammation.

Is serum Interleukin-17 associated with early atherosclerosis in obese patients?

Atherosclerosis is a chronic inflammatory process of the vessel walls, and CD4+ T-cells are peculiar to both human and murine atherosclerotic lesions. There is a recent line of research favoring hypothetic allergic mechanisms in the genesis of atherosclerosis and, consequently, coronary artery disease (CAD), among which Interleukin (IL)-17 appears to be a key cytokine regulating local tissue inflammation. The objective was to add a piece of information on the role of IL-17 in the genesis of atherosclerosis. Eighty obese patients with normal liver enzyme levels but presenting with ultrasonographic evidence of NAFLD formed the population of this cross-sectional study. Anthropometric measures, data on excess adiposity, metabolic profile, serum concentrations of IL-17, eotaxin-3, IL-8, and CCL4/MIP1ß, C-reactive protein, fibrinogen, ferritin, TNF-α, as well carotid intima-media thickness (IMT), a marker of atherosclerosis, and the main risk factors for CAD, such as blood pressure and smoking status, but also less determinant ones such as degree of NAFLD severity, Intramuscular Triglyceride storage and Resting Metabolic Rate were evaluated. Serum concentrations of Il-17 were detected as related to those of inflammatory cytokines, IL-6, IFN-γ and TNF-α. Furthermore, circulating levels of IL-17 were linked to those mirroring allergic process, IL-8, CCL4/MIP1ß and eotaxin. Early atherosclerosis, evidenced as increased IMT, was not associated with circulating IL-17 levels. At multiple regression,IMT was predicted, other than by age, by the amount of the visceral adiposity, expressed as visceral adipose tissue at ultrasonography, and by serum eotaxin. In conclusion, a strong relationship was found between the IL-17-related chemokine eotaxin and IMT. The association found between the amount of visceral fat and circulating levels of eotaxin on the one hand, and IMT on the other, could reinforce the hypothesis that IL-17, released by the visceral adipose tissue, induces eotaxin secretion via the smooth muscle cells present in the atheromatosus vessels.

Reduced Pharmacological Intervention of Prehospital Services for Acute Alcohol Intoxication during the COVID-19 Pandemic in A Large District of Southern Italy.

Background Stress during a pandemic increases the risk of alcohol consumption, which may require pharmacological management. Methods An observational single-center retrospective study was conducted from 1 January 2018 to 31 December 2021, and divided into 2-year periods (2018-2019 and 2020-2021). This study focused on calls to one of the emergency departments (EDs) of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ESs) who were either admitted or not admitted, due to their refusal. Results A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, an inverse association was found between pharmacological treatment and number of calls coded green (non-critical) and yellow (fairly critical) in patients admitted to EDs. An inverse association was also found for calls coded green in patients not admitted to EDs and pharmacological treatment. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. Conclusions ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

Are hepatic steatosis and carotid intima media thickness associated in obese patients with normal or slightly elevated gamma-glutamyl-transferase?

BACKGROUND: Hepatic steatosis (HS) has been associated with obesity and metabolic syndrome (MS), conditions carrying a high risk of coronary artery disease. We aimed to determine whether HS was an independent factor of atherogenic risk beyond its association with MS and its components. METHODS: We assessed the circulating levels of the heat shock protein-70 (HSP-70), a chaperone involved in inflammation, endoplasmic reticulum stress and apoptosis at liver and endothelial level and the gamma-glutamyl transferase activity (γ-GT) correlating them to carotid intima-media thickness (IMT), along with lipid profile, HOMA, C-reactive protein, fibrinogen, ferritin, adiposity type as well as spleen volume in 52 obese pts with grade 1, 128 with grade 2, and 20 with grade 3 of HS evaluated by sonography. RESULTS: Patients with different grade of HS demonstrated overlapping HSP-70 levels; similarly performed obese subjects regarding IMT. Using multiple regression analysis, IMT was predicted by age, visceral adiposity and by HOMA (ß = 0.50, p < 0.0001, ß = 0.30, p = 0.01 and ß = 0.18, p = 0.048 respectively, while the severity of HS was predicted by visceral and subcutaneous adiposity and HOMA (ß = 0.50, p < 0.0001 and ß = 0.27, p = 0.001 and ß = 0.18, p = 0.024, respectively). CONCLUSION: In our series of patients with normal or mild elevation of γ-GT, the severity of HS does not entail higher IMT, which may be linked to MS stigmata.

Acute alcohol intoxication across different age groups in 2014-2018: Prehospital care and biochemical correlates at a large University Hospital in southern Italy.

BACKGROUND: Risky alcohol consumption can occur from a young age and affects people of all age groups, sometimes requiring the intervention of the emergency medical services. OBJECTIVES: Determining the timing and characteristics of emergency calls (to the "118" emergency number) relating to subjects in all age groups, in which alcohol was a contributing factor, along with the biochemical correlates, in a great metropolitan area. On the basis of these, future interventions would target specific training for nurses and paramedics working in emergency medical services. METHOD: An observational single-centre retrospective study carried out from 1 January 2014 to 31 December 2018 involving patients requiring emergency care and attending the Emergency Department of an University Hospital. RESULTS: Out of a total of 47,252 emergency calls, 2.22% were for alcohol-related conditions and mainly involved male patients (78.4%). A high incidence of alcoholic coma was found in patients aged 11 to 17 years. Emergency medical assistance was required mainly at night on weekdays by patients aged 11-17, 25-44 years and during the weekend and on weekdays by patients aged 18-24 years. A blood alcohol concentration higher than 50 mg/dL was found in more than 67% of patients aged 11-17 and 18-24 years at weekends. CONCLUSIONS: The most alarming finding from our data is that, despite prevention policies, young people requiring emergency medical assistance showed similar alcohol levels as adults and a high incidence of alcoholic coma.

Metabolic Syndrome, Alzheimer's Disease, and Covid 19: A Possible Correlation.

Age and comorbidities are key indicators of hospital admission, serious illness, and mortality in COVID-19 patients. Patients with age-related comorbidities, such as cardiovascular disease, hypertension, diabetes, chronic kidney disease, NAFLD, obesity, and metabolic syndrome, are more likely to require hospitalization and suffer severe sickness of COVID-19. Patients with Alzheimer's disease and risk factors associated with dementia may also be more vulnerable to serious COVID-19 infection. Peripheral inflammation, including in patients who recover from illness, may promote the course of neurodegenerative disorders through neuroinflammatory pathways. The aim of this study is to examine the impact of COVID-19 on immunity in patients with age-related diseases such as metabolic syndrome and Alzheimer's disease and also to hypothesize the possible correlation between metabolic syndrome, Alzheimer's disease, and COVID-19. Identifying the mechanisms that explain the complicated interaction between metabolic syndrome, Alzheimer's disease, COVID-19, inflammation, and immunity could be crucial to designing effective pharmacological therapies and procedures. This study adds to our basic information about the new coronavirus by synthesizing current knowledge of these linkages. To reduce inflammation and enhance immunity, patients should acquire good lifestyle practices. Walking, breathing exercises, and a nutritious diet all help in improving lung capacity and immunity. Future research into novel therapeutics for patients with metabolic syndrome, Alzheimer's disease, and COVID-19 inflammation and immunology is encouraged by this paper.

Characterization of Student Drinking Behaviors at the Beginning of the First Academic Year at One University in Southern Italy.

It is well recognized that both college and noncollege students are at-risk age groups for alcohol consumption. We investigated the alcohol consumption habits of undergraduate students with an emphasis on binge drinking. Participants (N = 809, 61.2% female) were freshmen attending courses at one of the main universities of southern Italy. They were asked to fill out a paper-and-pencil questionnaire that was administered between October 2017 and January 2018. Nearly 90% of the questioned students reported drinking alcohol during the 12 months before the survey. Among them, 31.4% of female students and 41.5% of male students engaged in binge drinking, mainly once a month; binge drinkers preferred highly alcoholic beverages during parties, underestimated the alcoholic content of their drinks, started drinking alcohol at a younger age than nonbinge drinkers, and drank weekly and between meals. Binge drinkers started smoking earlier than their peers, and a great number of them consumed illicit drugs. Moreover, 30.3% of female and 34.8% of male nonbinge drinkers declared that they consumed 6 or more units of alcohol in one occasion, making them unaware binge drinkers. Furthermore, approximately 50% of students recognized that alcohol consumption has effects similar to those induced by illicit drugs but only considered their peers' drinking behavior to be risky.This study highlights that most students involved in this survey expose themselves to a risky lifestyle by heavy drinking and, most alarmingly, that some of them are not even aware of that.

Corrigendum to "Sequence Analysis of the UCP1 Gene in a Severe Obese Population from Southern Italy".

[This corrects the article DOI: 10.1155/2011/269043.].

Corrigendum to "Circulating Levels of Sirtuin 4, a Potential Marker of Oxidative Metabolism, Related to Coronary Artery Disease in Obese Patients Suffering from NAFLD, with Normal or Slightly Increased Liver Enzymes".

[This corrects the article DOI: 10.1155/2014/920676.].

Metabolic and nutritional status changes after 10% weight loss in severely obese patients treated with laparoscopic surgery vs integrated medical treatment.

BACKGROUND: Bariatric surgery is considered the most effective treatment for reducing excess body weight and maintaining weight loss (WL) in severely obese patients. There are limited data evaluating metabolic and body composition changes after different treatments in type III obese (body mass index [BMI] > 40 kg/m(2)). METHODS: Twenty patients (9 males, 11 females; 37.6 +/- 8 years; BMI = 50.1 +/- 8 kg/m(2)) treated with dietary therapy and lifestyle correction (group 1) have been compared with 20 matched patients (41.8 +/- 6 years; BMI = 50.4 +/- 6 kg/m(2)) treated with laparoscopic gastric bypass (LGBP; group 2). Patients have been evaluated before treatment and after >10% WL obtained on average 6 weeks after LGBP and 30 weeks after integrated medical treatment. Metabolic syndrome (MS) was evaluated using the Adult Treatment Panel III/America Heart Association (ATP III/AHA) criteria. Resting metabolic rate (RMR) and respiratory quotient (RQ) was assessed with indirect calorimetry; body composition with bioimpedance analysis. RESULTS: At entry, RMR/fat-free mass (FFM) was 34.2 +/- 7 kcal/24 h.kg in group 1 and 35.1 +/- 8 kcal/24 h.kg in group 2 and did not decrease in both groups after 10% WL (31.8 +/- 6 vs 34.0 +/- 6). Percent FFM and fat mass (FM) was 50.7 +/- 7% and 49.3 +/- 7% in group 1 and 52.1 +/- 6% and 47.9 +/- 6% in group 2, respectively (p = n.s.). After WL, body composition significantly changed only in group 1 (% FFM increased to 55.9 +/- 6 and % FM decreased to 44.1 +/- 6; p = 0.002). CONCLUSION: After >10% WL, MS prevalence decreases precociously in surgically treated patients; some improvements in body composition are observed in nonsurgically treated patients only. Further investigations are needed to evaluate long-term effects of bariatric surgery on body composition and RMR after stable WL.

Retraction: Nonalcoholic fatty liver disease, diet and gut microbiota.

[This retracts the article on p. 461 in vol. 13, PMID: 26417275.].

The mtDNA 15497 G/A polymorphism in cytochrome b in severe obese subjects from Southern Italy.

BACKGROUND AND AIM: A large number of mitochondrial DNA (mtDNA) mutations have been implicated in degenerative diseases and aging. The aim of this study was to evaluate whether the 15497 G/A mtDNA polymorphism (G251S) in the cytochrome b subunit of respiratory complex III, which has been associated with obesity-related variables and lipid metabolism in a Japanese population, is associated with severe obesity also in adult Caucasians from southern Italy. METHODS AND RESULTS: Unrelated severely obese patients (n = 317; BMI > 40kg/m2) and controls (n = 217; BMI < 25kg/m2) from Southern Italy were genotyped by allelic discrimination TaqMan assay for the 15497 G/A mtDNA polymorphism. In obese patients fasting serum total cholesterol, triglycerides, HDL-cholesterol and glucose were measured enzymatically and sitting blood pressure and heart rate were also collected. Mean levels of total cholesterol, triglycerides and glucose were below the upper reference limit for healthy subjects. Female obese subjects showed lower levels of blood pressure and heart rate and higher levels of HDL cholesterol than male obese patients (P < 0.001). All the control subjects and 315/317 severely obese patients were homozygous for the G allele (wild type), whereas only 2/317, were females homozygous for the A allele. CONCLUSIONS: The mtDNA 15497 G/A polymorphism in cytochrome b was present in 0.6% obese subjects, two females whose lipid parameters and BMI were similar to those of the overall group. Therefore, this mutation may appear to contribute in rare instances to severe obesity but does not explain the majority of cases in our population. A more extensive genetic haplogroup characterization is required to identify associations to obesity in Caucasians.

Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease.

BACKGROUND: The gut microbiota is modulated by metabolic derangements, such as nutrition overload and obesity. AIM: The aim of this systematic review is to summarize the role of these gut modifiers in nonalcoholic fatty liver disease (NAFLD) and obesity. METHODS: A systematic search of MEDLINE (from 1946), PubMed (from 1946) and EMBASE (from 1949) databases through May 2014 was carried out to identify relevant articles. The search terms were 'probiotic' AND 'NAFLD', 'prebiotic' AND 'NAFLD', 'antibiotic' AND 'NAFLD', 'probiotics' AND 'obesity', 'prebiotic' AND 'obesity' or 'antibiotic' AND 'obesity'; these terms were searched as text word in 'clinical trials' and as exploded medical subject headings where possible. RESULTS: The evidence in the literature is scant, due to the scarcity of appropriately powered, randomized, controlled clinical trials, involving various centers and population of different origin. CONCLUSION: Although probiotics and prebiotics have been proposed in the treatment and prevention of patients with obesity-related NAFLD, their therapeutic use is not supported by high-quality clinical studies.

Hype or Reality: Should Patients with Metabolic Syndrome-related NAFLD be on the Hunter-Gatherer (Paleo) Diet to Decrease Morbidity?

The current Western diet figures centrally in the pathogenesis of several chronic diseases such as obesity, type 2 diabetes, cardiovascular disease and the emerging major health problem nonalcoholic fatty liver disease, all of them negatively impacting on life expectancy. This type of diet is represented by a high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of fructose. On the contrary, a simplified way of eating healthily by excluding highly-processed foods, is presumed to be the Paleolithic diet (a diet based on vegetables, fruits, nuts, roots, meat, organ meats) which improves insulin resistance, ameliorates dyslipidemia, reduces hypertension and may reduce the risk of age-related diseases. The diet is the foundation of the treatment of obesity- and type 2 diabetes-related nonalcoholic fatty liver disease and a diet similar to those of pre-agricultural societies may be an effective option. To lend sufficient credence to this type of diet, well-designed studies are needed.

Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone/insulin-like growth factor-1 status.

BACKGROUND: The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions. In obesity both GH/IGF-1 status and serum Sirt4 levels, likely mirroring its reduced mitochondrial expression, might be altered. OBJECTIVE: To evaluate the association between circulating levels of Sirt4, body composition, metabolic parameters and cardio-metabolic risk profile in obese patients according to their different GH/IGF-1 status. DESIGN: Cross-sectional study with measurement of serum Sirt4, GH after GH releasing hormone (GHRH)+Arginine test, IGF-1 and assessment of body composition, glucose and lipid metabolism in 50 class II-III obese subjects (BMI 35.6 to 62.1 kg/m(2)) and 15 normal weight subjects. Low GH secretion and IGF-1 were defined using pre-determined cutoff-points. The Homeostatic Metabolic Assessment of insulin resistance index and Visceral adiposity index were also calculated. The association of Sirt4 with peak stimulated GH and IGF-1, body composition, metabolic parameters and cardio-metabolic risk profile was assessed. RESULTS: Serum Sirt4 was inversely related to anthropometric and metabolic parameters and positively related to peak GH and IGF-1. After adjusting for peak GH and IGF-1, the relationships between Sirt4 and BMI became not significant. At multiple regression analysis IGF-1 (p<0.001) was the independent predictor for Sirt4. CONCLUSION: There was a close relationship between low IGF-1 and low serum Sirt4. This observation suggested that in obese patients, low GH/IGF-1 status was likely associated with a major compensatory decrease in circulating levels of Sirt4 to oppose to its negative regulator effect on mitochondrial oxidative capacity.