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Background: Very Low-Calorie Ketogenic Diet (VLCKD) is currently a promising approach for the treatment of obesity. However, little is known about the side effects since most of the studies reporting them were carried out in normal weight subjects following Ketogenic Diet for other purposes than obesity. Thus, the aims of the study were: (1) to investigate the safety of VLCKD in subjects with obesity; (2) if VLCKD-related side effects could have an impact on its efficacy., Methods: In this prospective study we consecutively enrolled 106 subjects with obesity (12 males and 94 females, BMI 34.98 ± 5.43 kg/m 2 ) that underwent to VLCKD. In all subjects we recorded side effects at the end of ketogenic phase and assessed anthropometric parameters at the baseline and at the end of ketogenic phase. In a subgroup of 25 subjects, we also assessed biochemical parameters., Results: No serious side effects occurred in our population and those that did occur were clinically mild and did not lead to discontinuation of the dietary protocol as they could be easily managed by healthcare professionals or often resolved spontaneously. Nine (8.5%) subjects stopped VLCKD before the end of the protocol for the following reasons: 2 (1.9%) due to palatability and 7 (6.1%) due to excessive costs. Finally, there were no differences in terms of weight loss percentage (13.5 ± 10.9% vs 18.2 ± 8.9%; p = 0.318) in subjects that developed side effects and subjects that did not developed side effects., Conclusion: Our study demonstrated that VLCKD is a promising, safe and effective therapeutic tool for people with obesity. Despite common misgivings, side effects are mild, transient and can be prevented and managed by adhering to the appropriate indications and contraindications for VLCKD, following well-organized and standardized protocols and performing adequate clinical and laboratory monitoring., (© 2022. The Author(s).)

Obesity is a major public health issue, and its trend is increasing worldwide. Interventions to effectively treat obesity and its related diseases are advocated. Given the complexity of obesity management, nurses need specific core skills to work in the Obesity Clinic and can act as key players in the multidisciplinary team of the Obesity Clinic. To provide practical guidelines for nurses working in Obesity Clinic for effective management of obesity and its related diseases, the current evidence on the role nurses in the obesity clinic was reviewed. Nurses can play a pivotal role in the management of patients with obesity and associated diseases that may require a stricter follow-up than usual care. Given the complexity of the treatment of obesity and its comorbidity, nurses should receive a specific training for: 1) methods and tools to effectively treat obesity and obesity-related disease; 2) patients and families education on nutrition, lifestyle changes, and prevention/management of obesity-related diseases; 3) motivation of patients towards adherence to treatment to achieve their specific goals. This review highlights the need of specific core skills for nurses working in the Obesity Clinic.

Obesity and obesity-related low-grade inflammation are common findings in polycystic ovary syndrome (PCOS), the most common endocrine-metabolic disorder-affecting women in reproductive age. The terms metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) have been introduced to define individuals with obesity in whom cardio-metabolic risk factors are absent or present, respectively. To date, evidence investigating differences in body composition and adherence to the Mediterranean diet (MD) between MHO and MUO-PCOS women are lacking. Aim of this study was to better characterize the determinants of the metabolic health status in PCOS patients with obesity according to MHO and MUO phenotypes by evaluating endocrine-metabolic profile, inflammatory status, adherence to the MD, and body composition. The study population consisted of 94 treatment-naïve women with PCOS and obesity (BMI = 38.23 ± 6.62 kg/m 2 and age = 24.12 ± 3.68 years). Compared PCOS MHO with PCOS MUO patients, the latter had higher levels of high-sensitivity C-reactive protein (hs-CRP) ( p < 0.001), testosterone ( p < 0.001), and insulin ( p < 0.001), worse metabolic parameters, and higher Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), Visceral Adiposity Index (VAI), and Fatty liver Index (FLI) ( p < 0.001). Furthermore, PCOS MUO patients had lower adherence to the MD ( p < 0.001) in spite of the same total energy intake ( p = 0.102) as compared to PCOS MHO. The presence of MUO was associated with highest hs-CRP levels (OR = 1.49, p < 0.001), more severe hyperandrogenism and cardio-metabolic indices ( p < 0.001). On the contrary, being PCOS MUO was associated with lower adherence to the MD (OR = 0.28, p < 0.001), and smaller PhAs (OR = 0.04, p < 0.001). Using a regression linear analysis model PREDIMED score entered at the first step ( p < 0.001), followed by VAI ( p < 0.001), and FLI ( p = 0.032) in this analysis. At ROC analysis, a PREDIMED score of ≤4 ( p < 0.001, AUC 0.926) could serve as a threshold for a significantly increased risk of presence the MUO-PCOS phenotype. To the best of our knowledge, this is the first study that characterized MHO and MUO-PCOS women on the basis of their adherence to the MD, body composition, and cardio-metabolic indices, providing evidence of the usefulness of adjunctive diagnostic parameters to better differentiate the MHO/MHO phenotypes in this cohort of PCOS patients with obesity.

Over the last few years, the complexity and diversity of gut microbiota within and across individuals has been detailed in relation to human health. Further, understanding of the bidirectional association between gut microbiota and metabolic disorders has highlighted a complimentary, yet crucial role for microbiota in the onset and progression of obesity-related cancers. While strategies for cancer prevention and cure are known to work efficiently when supported by healthy diet and lifestyle choices and physical activity, emerging evidence suggests that the complex interplay relating microbiota both to neoplastic and metabolic diseases could aid strategies for cancer treatment and outcomes. This review will explore the experimental and clinical grounds supporting the functional role of gut microbiota in the pathophysiology and progression of cancers in relation to obesity and its metabolic correlates. Therapeutic approaches aiding microbiota restoration in connection with cancer treatments will be discussed., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The aim of the study was to investigate the association of chronotype categories with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) in 172 middle-aged adults (71.5% females; 51.8 ± 15.7 years). Anthropometric parameters, lifestyle habits, adherence to the Mediterranean Diet (MD), sleep quality, chronotype and the presence of T2DM and CVD were studied. Chronotype was classified as morning in 58.1% of subjects, evening in 12.8% and intermediate in 28.1%. Subjects with evening chronotype followed an unhealthier lifestyle than other chronotypes; indeed, they significantly performed less regular activity and were more frequently smokers. Furthermore, they had significantly higher risk to have T2DM [Odds Ratio (OR)=3.36 95% confidence interval (CI) 1.14-35.42; p  = 0.03] and CVD [Odds Ratio (OR)= 5.89 95% CI 1.14-30.60; p  = 0.035](CI) 2.24-407.54); p  = 0.01] compared to morning chronotype after adjustment for gender, body mass index (BMI), sleep quality and adherence to the MD. The confidence intervals were wide, indicating that the sample size was too small. Thus, these data need to be replicated in a larger sample size. In addition, nutritional assessment was limited since only PREDIMED questionnaire was carried out. However, the main strengths of this study included a random sample and a population-based approach, although the cross-sectional design cannot establish causality. Although study population was unbalanced per gender and smoking and age group representing only middle-aged people,we adjusted the statistical analysis for potential confounding factors. In conclusion, the evening chronotype has an increased risk to be associated to T2DM and CVD.

Chronotype is defined as the behavioral manifestation of circadian rhythms related to the external light-dark cycle. Evening chronotype has been associated with an increased risk of developing cardiometabolic diseases in obesity. Menopause is a lifestage associated with an increased risk of developing cardiometabolic diseases and a change in circadian rhythmicity compared to pre-menopause. However, the prevalence of chronotype categories in menopause and their role in determining menopause-related cardiometabolic risk, mostly in obesity, have not been investigated. Thus, we aimed to investigate the prevalence of chronotype categories in post-menopausal women with obesity and their role in menopause-related cardiometabolic risk. In this cross-sectional study we enrolled 49 pre-menopausal and 74 post-menopausal women with obesity. Anthropometric parameters, lifestyle habits, adherence to the Mediterranean Diet (MD), sleep quality, chronotype and the presence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) were studied. No significance differences were detected in terms of lifestyle and adherence to the MD between pre- and post-menopausal women. Chronotype was classified as morning in 66 (53.6%), evening in 20 (16.3%) and intermediate in 37 (30.1%) women. In addition, pre-menopausal women with obesity showed a significantly higher chance to have an intermediate chronotype (OR = 2.21, 95% CI 1.28-3.83; p = 0.004), whereas post-menopausal women with obesity showed a trend to have a higher morning chronotype (OR = 1.42, 95% CI 0.98-2.06; p = 0.051), although this did not reach statistical significance. No significant differences were detected in terms of prevalence of evening chronotype between the two groups. However, the evening chronotype had a significantly higher risk to have T2DM compared to the morning (OR = 17.29, 95% CI 2.40-124.27; p = 0.005) and intermediate chronotypes (OR = 30.86, 95% CI 2.05-464.32; p = 0.013) in both pre- and post-menopausal women with obesity. In conclusion, the intermediate chronotype was significantly more prevalent in pre-menopausal women with obesity compared to post-menopausal women. Evening chronotype was associated to T2DM in both pre- and post-menopause. These results support the importance of including the assessment of chronotype in the management of women with obesity in post-menopause.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect. Clinical picture of PWS changes across life stages. The main clinical characteristics are represented by short stature, developmental delay, cognitive disability and behavioral diseases. Hypotonia and poor suck resulting in failure to thrive are typical of infancy. As the subjects with PWS age, clinical manifestations such as hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency due to hypothalamic dysfunction occur. Obesity and its complications are the most common causes of morbidity and mortality in PWS. Several mechanisms for the aetiology of obesity in PWS have been hypothesized, which include aberration in hypothalamic pathways of satiety control resulting in hyperphagia, disruption in hormones regulating appetite and satiety and reduced energy expenditure. However, despite the advancement in the research field of the genetic basis of obesity in PWS, there are contradictory data on the management. Although it is mandatory to adopt obesity strategy prevention from infancy, there is promising evidence regarding the management of obesity in adulthood with current obesity drugs along with lifestyle interventions, although the data are limited. Therefore, the current manuscript provides a review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management., (© 2021. The Author(s).)

The number of cancers attributed to obesity is increasing over time. The mechanisms classically implicated in cancer pathogenesis and progression in patients with obesity involve adiposity-related alteration of insulin, sex hormones, and adipokine pathways. However, they do not fully capture the complexity of the association between obesity-related nutritional imbalance and cancer. Gut hormones are secreted by enteroendocrine cells along the gastrointestinal tract in response to nutritional cues, and act as nutrient sensors, regulating eating behavior and energy homeostasis and playing a role in immune-modulation. The dysregulation of gastrointestinal hormone physiology has been implicated in obesity pathogenesis. For their peculiar function, at the cross-road between nutrients intake, energy homeostasis and inflammation, gut hormones might represent an important but still underestimated mechanism underling the obesity-related high incidence of cancer. In addition, cancer research has revealed the widespread expression of gut hormone receptors in neoplastic tissues, underscoring their implication in cell proliferation, migration, and invasion processes that characterize tumor growth and aggressiveness. In this review, we hypothesize that obesity-related alterations in gut hormones might be implicated in cancer pathogenesis, and provide evidence of the pathways potentially involved., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Over the past decades, there has been an increase in overweight and obesity worldwide rates in both in adult and children. In parallel, it has been reported a worsening of sleep duration and quality. Some studies have shown an association between obesity and sleep disturbances (SD) vice versa, subjects with obesity have a greater risk of SD. As well as SD influences diet, also food choices have been shown to influence various sleep-related variables, such as duration and quality. For this reason, nutrition could represent an important tool not only to lose weight but also to improve sleep in patients with obesity and sleep disturbances. Thus, the aim of this review is to provide an overview of the studies that assessed the association between obesity and SD and vice versa , highlighting possible nutritional advices as a tool to improve sleep in patients with obesity and sleep disturbances.

Emerging data suggest an association between obesity and infectious diseases. Although the mechanisms underlying this link are not well established, a number of potential factors may be involved. Indeed, the obesity-related vulnerability to infectious diseases could be due to chronic low-grade inflammation, hyperglycemia, hyperinsulinemia, and hyperleptinemia, which lead to a weakening of both the innate and adaptive immune responses. In addition, obesity results in anatomical-functional changes by the mechanical obstacle of excessive adipose tissue that blunt the respiratory mechanisms and predisposing to respiratory infections. Subjects with obesity are also at risk of skin folds and sweat more profusely due to the thick layers of subcutaneous fat, favoring the proliferation of microorganisms and slowing the repair of wounds down. All these factors make subjects with obesity more prone to develop nosocomial infections, surgical site, skin and soft tissue infections, bacteremia, urinary tract infections, and mycosis. Furthermore, infections in subjects with obesity have a worse prognosis, frequently prolonging hospitalization time as demonstrated for several flu viruses and recently for COVID-19. Thus, the aim of this manuscript is to provide an overview of the current clinical evidence on the associations between obesity and infectious diseases highlighting physio pathological insights involved in this link., (© 2021 World Obesity Federation.)

Purpose: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy., Methods: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated., Results: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ 2  = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ 2  = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R 2  = 0.060; IC 1.00-1.10). Headache (62.8% vs. 31.6%; χ 2  = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ 2  = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ 2  = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI., Conclusions: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA.

The OPERA (Obesity, Programmes of nutrition, Education, Research and Assessment of the best treatment) PREVENTION PROJECT was a campaign of prevention of obesity that was held on October 11th-13th 2019 in Naples. The project was based on the organization of a medical, athletic, tasting and psychological path with the following objectives: 1) Providing a free medical examination to subjects with obesity; 2) providing athletic advices to perform physical activity; 3) performing a show-cooking in order to teach subjects with obesity to cook healthy food; 4) providing a gustatory and olfactory sensitivity assessment; 4) providing a psychological examination through questionnaires to evaluate obstacles to start a weight loss programme and to psycologically support subjects with obesity on a virtual journey made through a reshaping software programme. In conclusion the OPERA PREVENTION PROJECT could represent a health promotion intervention reproducible in all the countries having high rates of subjects with obesity and overweight.

Competing Interests: Declaration of competing interest All authors declare no conflict of interests.

The prevalence of obesity increases worldwide and has a significant economic impact on health care systems. A comprehensive program of lifestyle modification, including diet, exercise, and behavior therapy is considered the first option for achieving the significant weight loss. However, the intrinsic difficulties associated with maintenance of lifestyle changes contribute to the unsatisfactory long-term outcomes reported and weight regain in the obesity management. In this context, pharmacological approaches are useful to maximize non-pharmacological interventions in the long-term management of obesity. As add-on to lifestyle modification, pharmacological interventions are useful to facilitate clinically weight loss. In the past, anti-obesity drugs were limited. To date, the landscape has changed and naltrexone/bupropion and liraglutide have been recently added as new-generation anti-obesity drugs on obesity treatment and could represent important tools to manage of obesity. Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that shares 97% homology to native GLP-1 with effects on the limbic system. The treatment with liraglutide 3.0 mg, in combination with a hypocaloric diet and increased physical activity, provides a clinically meaningful weight loss. The combination of naltrexone 32 mg and bupropion 360 mg acts on the mesolimbic reward pathway and the hypothalamic hunger system, two areas of the central nervous system. The combination of naltrexone/bupropion, an adjunct to a hypocaloric diet and increased physical activity, is approved for chronic weight management in adults with obesity or overweight and ≥1 weight-related comorbidity. In the present review, we have focused on the current evidence on two new-generation anti-obesity drugs, naltrexone/bupropion and liraglutide 3.0 mg addressing the main studies that investigated these two new drugs for obesity treatment. Furthermore, evidence on semaglutide, currently in the pipeline for potential future therapeutic use for weight loss, are reported.

Obesity and unhealthy eating habits have been associated with sleep disturbances (SD). The Mediterranean diet (MD) is a healthy nutritional pattern that has been reported to be associated with better health and sleep quality. Thus, the aim of the study was to investigate whether adherence to the MD is associated with sleep quality in a population of middle-aged Italian adults. This cross-sectional study included 172 middle-aged adults (71.5% females; 51.8 ± 15.7 years) that were consecutively enrolled in a campaign to prevent obesity called the OPERA (Obesity, Programs of Nutrition, Education, Research and Assessment of the best treatment) prevention project that was held in Naples on 11-13 October 2019. Anthropometric parameters, adherence to the MD and sleep quality were studied. Overall, 50.6% of the subjects were good sleepers (the Pittsburgh Sleep Quality Index (PSQI) < 5) while 49.4% were poor sleepers (PSQI ≥ 5). Our results demonstrated that good sleepers, when compared to poor sleepers ( p < 0.001) had significantly higher adherence to the MD as assessed by PREDIMED (Prevención con Dieta Mediterránea) score, lower BMI (body mass index) and waist circumference (WC). The higher PSQI, the higher the BMI ( p < 0.001) and WC values ( p < 0.001), thus suggesting that poor sleep was more common in subjects with obesity. In addition, a negative correlation between PSQI and the PREDIMED score ( p < 0.001) was found. to the intake of the cluster of foods enclosed in the MD, rather than the intake of the single food, predicted PSQI. By performing a receiver operator characteristic (ROC) curve analysis, we determined a cut-off value at a PREDIMED score < 9 as the threshold for screening poor sleepers. In conclusion, good sleepers had lower BMI and WC and higher adherence to the MD than poor sleepers. PSQI was positively associated to BMI and WC while it was negatively associated to adherence to the MD. The consumption of the MD dietary pattern rather than the intake of a single nutrient has a beneficial effect on sleep quality. Hence, the assessment of sleep should be taken into account in the management of obesity and promoting adherence to the MD could be a tool to improve SD.

Chronotype is the attitude of a subject in determining individual circadian preference in behavioral and biological rhythm relative to the external light-dark cycle. Obesity and unhealthy eating habits have been associated with evening chronotype. The Mediterranean diet (MD) is a healthy nutritional pattern that has been reported to be associated with better health and quality of sleep. Thus, the aim of the study was to investigate the association of chronotype categories with adherence to the MD in a population of middle-aged Italian adults. This cross-sectional study included 172 middle-aged adults (71.5% females; 51.8 ± 15.7 years) that were consecutively enrolled in a campaign to prevent obesity called the OPERA (obesity, programs of nutrition, education, research and assessment of the best treatment) Prevention Project that was held in Naples on 11-13 October 2019. Anthropometric parameters, adherence to the MD and chronotype were studied. Chronotype was classified as morning in 58.1% of subjects, evening in 12.8% and intermediate in 28.1%. Our results demonstrated that individuals with evening chronotype, when compared to intermediate ( p < 0.001) and morning chronotype ( p < 0.001), were more prone to follow unhealthy lifestyle, performing less regular activity and being more frequently smokers. In addition, they showed the lowest adherence to the MD compared to morning ( p < 0.001) and intermediate chronotypes ( p < 0.001). The lower the chronotype score, the higher body mass index (BMI) values in the whole population (r = -0.158; p = 0.038), thus suggesting that evening chronotype was a common finding in subjects with obesity. In addition, positive correlations of chronotype score with age (r = 0.159; p = 0.037) and PREDIMED score (r = 0.656; p < 0.001) were found. The adherence to the MD, more than the intake of the single food items, was found to predict morning and evening chronotypes. In conclusion, evening chronotype was associated with unhealthy lifestyle and low adherence to the MD. Chronotype score was inversely associated to BMI and positively associated to age and adherence to the MD. Thus, the assessment of chronotype should be taken into account in the management of obesity and in the development of nutritional strategies.

Purpose of Review: Obstructive sleep apnea (OSA), obesity, and disturbed glucose homeostasis are usually considered distinct clinical condition, although they are tightly related to each other. The aim of our manuscript is to provide an overview of the current evidence on OSA, obesity, and disturbed glucose homeostasis providing epidemiologic evidence, biological insights, and therapeutic strategies., Recent Findings: The mechanisms hypothesized to be involved in this complex interplay are the following: (1) "direct weight-dependent" mechanisms, according to which fat excess compromises respiratory mechanics, and (2) "indirect weight-dependent" mechanisms such as hyperglycemia, insulin resistance and secondary hyperinsulinemia, leptin resistance and other hormonal dysregulations frequently found in subjects with obesity, type 2 diabetes, and/or sleep disorders. Moreover, the treatment of each of these clinical conditions, through weight loss induced by diet or bariatric surgery, the use of anti-obesity or antidiabetic drugs, and continuous positive airway pressure (CPAP), seems to positively influence the others. These recent data suggest not only that there are multiple connections among these diseases but also that treating one of them may result in an improvement of the others.

Background: Hypovitaminosis D and higher platelet numbers are emerging as cardiovascular risk factors, in particular in obese subjects., Methods: This observational study was aimed at investigating the relationship between platelet number and serum 25-hydroxyvitamin D (25(OH)D) levels in a cohort of individuals affected by overweight and obesity (body mass index (BMI) ≥ 25 Kg/m 2 ). A sample of 341 subjects (248 women, 93 men), aged 18-71 years, taking no medication, was examined. Anthropometric, hormone, metabolic and common routine hematochemical parameters were examined and evaluated in association with platelet count and serum 25(OH)D levels., Results: Platelet numbers were inversely related to age ( p < 0.04), 25(OH)D ( p < 0.05) and uric acid ( p < 0.04) levels, and directly associated with white blood cells ( p < 0.01), Thyroid Stimulating Hormone (TSH) ( p < 0.04), insulin levels ( p < 0.002) and Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) ( p < 0.002). We applied statistical regression models to examine the relationship between platelet count (dependent variable) and parameters that had univariate associations with platelet numbers, showing that the association between platelet count and 25(OH)D was not confirmed. Moreover, vitamin D showed a negative independent association with BMI, diastolic blood pressure and serum insulin levels., Conclusions: This study indicates, for the first time, that vitamin D deficiency is associated with a parallel increase in platelet number, suggesting that higher platelet numbers may be one of the possible mechanisms leading to a greater cardiovascular risk in obese subjects. It also shows that vitamin D deficiency, a common condition in obesity, has independent associations with higher BMI, diastolic blood pressure and serum insulin levels., Competing Interests: The authors declare no conflict of interest.

Growing evidence reported that vitamin D deficiency is a common finding in obesity. Vitamin D status also seems to be sex-related, although little is known regarding this association. Therefore, the aim of this study was to investigate the sex-related differences of serum 25OH vitamin D (25OHD) concentrations across body mass index (BMI) classes and, if there were any differences, whether they could be explained by sex-related differences in body composition. We enrolled 500 subjects (250 males, age 37.4 ± 11.8 years; 250 females, age 36.6 ± 11.8 years). Body composition was assessed by bioelectrical impedance analysis (BIA) phase-sensitive system. Serum 25OHD concentration was quantified by a direct, competitive chemiluminescence immunoassay. Vitamin D deficiency was defined as a serum 25OHD concentrations < 20 ng/mL (50 nmol/L). Stratifying the sample population according to sex and BMI categories, 25OHD concentrations were significantly higher in males compared to females in all BMI classes and decreased along with the increase of BMI values. Females with vitamin D deficiency had higher fat mass (FM) % compared to males with vitamin D deficiency. The 25OHD concentrations inversely correlated with FM % in both sexes. In a multiple regression analysis model, sex, FM %, and BMI were predictive factors of 25OHD concentration. In conclusion, our study suggests that 25OHD concentrations were lower in females than males across all BMI categories. Given the tight correlation between 25OHD concentrations and FM %, it can be hypothesized that the lower 25OHD concentrations in females than males can be explained by the fact that females have a higher amount of fat than males.

There is accumulating evidence showing that obesity is due not merely to increased food intake, but could have a more complex pathophysiology possibly originating from the gut. Due to its microbiological, hormonal, and nutritional aspects, the gut could represent a starting point for the treatment of weight excess. Obesity is associated with a change of microbiota composition that not only could increase the calorie extraction from food but also could create a functional derangement resulting in irritable bowel syndrome (IBS). Several mechanisms have been postulated to explain this association, such as specific foods that are poorly absorbed, i.e., carbohydrates and lipids, as well as conditions of psychological stress which could stimulate colonic hypersensitivity giving rise to IBS symptoms. Another factor involved in this link could be the subclinical inflammation typical of obesity, characterized by the release of inflammatory mediators that can irritate intestinal nerve endings. The change of levels of some anorexigenic hormones, as well as the alterations of the gut microbiota with the reduction of the bacteroides/Firmicutes ratio, could also contribute to the pathogenesis of IBS related to obesity. Thus, the aim of this manuscript is to review the current evidence on the association between obesity and IBS while providing physiopathological hypotheses that may explain this link. Further, we will report the effect of weight loss on IBS symptoms, highlighting the importance of an accurate assessment of gut function in obese patients.

The epidemic of obesity is growing steadily across the whole world. Obesity is not only a merely aesthetic disease but is the "mother" of most chronic diseases such as associated with a range of type 2 diabetes, cardiovascular disease, obstructive sleep apnea, and cancer. However, although there is a need to find a strategy to stop this epidemic disease, most of the times the current nutritional strategies are not effective in weight loss and in long term weight maintenance. Very low-calorie ketogenic diets (VLCKD) is increasingly establishing as a successful nutritional pattern to manage obesity; this is due to rapid weight loss that gives rise to a positive psychological cycle which in turn increases the compliance to diet. Another important key point of VLCKD is the ability to preserve fatty free mass which is known to play a role of paramount importance in glucose metabolism. Despite the clinical evidence of VLCKD there are paucity of data regarding to its management. Therefore, we will provide a useful guide to be used by nutrition experts taking care of subjects with obesity. In particular, we will report recommendations on the correct use of this therapeutic approach for weight loss and management of side effects.

Obesity is associated with reduced spontaneous and stimulated growth hormone (GH) secretion and basal insulin-like growth factor I (IGF-1) levels-which in turn is associated with increased prevalence of cardiovascular risk factors. The aim of this study was to investigate: (1) the association of somatotropic axis with cardiometabolic status; (2) the association of somatotropic axis with the Mediterranean diet and nutritional pattern in people with obesity. Cross-sectional observational study was carried out in 200 adult women, aged 36.98 ± 11.10 years with severe obesity (body mass index-BMI of 45.19 ± 6.30 kg/m 2 ). The adherence to the Mediterranean diet and the total calorie intake was assessed. Anthropometric measurements, body composition and biochemical profile were determined along with Growth Hormone (GH)/Insulin like Growth Factor 1 (IGF-1) axis and insulin resistance (homeostatic model assessment for insulin resistance-HoMA-IR). The enrolled subjects were compared after being divided according to GH peak response and according to IGF-1 standard deviation scores (SDS). Derangements of GH peak were detected in 61.5% of studied patients while IGF-1 deficiency was detected in 71% of the population. Both blunted GH peak response and IGF-1 SDS were indicators of derangements of somatotropic axis and were associated with comparable results in terms of cardiometabolic sequelae. Both GH peak and IGF-1 levels were inversely associated with anthropometric and metabolic parameters. The adherence to the Mediterranean diet predicts GH peak response. Fatty liver index (FLI), fat mass (FM) and phase angle (PhA) were predictive factors of GH peak response as well. In conclusion derangements of somatotropic axis is associated with a worse cardiometabolic profile in people with obesity. A high adherence to the Mediterranean diet-and in particular protein intake-was associated with a better GH status.

Study of the interactions between the gut microbiota and brain-gut axis represents a very appealing approach to increasing our knowledge about the mechanisms leading to obesity and obesity-related diseases. The aim of this review is to focus on the effects of short-chain fatty acids (SCFAs), which are the main products of gut microbial fermentation from non-digestible carbohydrates in the colon, on the gut-brain axis. Evidence is accumulating regarding the role of SCFAs in the fine-tuning of the gut-brain axis, a feedback system which is vital not only for the proper maintenance of gastrointestinal and metabolic functions, but also for the regulation of food intake and energy expenditure. SCFAs are thought to play a key role in increasing the host capacity to harvest excess energy from the diet. SCFAs, however, can exert their effects on the host metabolism via multiple complementary pathways. Metabolic, inflammatory, and neural pathways can be regulated by SCFAs, which can act by sensing nutritional status, thereby maintaining body energy homeostasis. SCFA production from prebiotic consumption is the rationale for targeting intestinal mechanisms to increase energy expenditure and thereby reduce obesity risk.

Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D levels with PhA in obesity, the aim of this study was to investigate their possible relationship in a group of patients with obesity stratified according to body mass index (BMI) categories. Four hundred and fifty-five adult subjects (219 males and 236 females; 36 ± 11 years) were enrolled. Body composition, including PhA, was assessed using a BIA phase-sensitive system. Serum levels of 25(OH)D was determined by a direct competitive chemiluminescence immunoassay. Most of the participants were affected by grade III obesity (24%) and had 25(OH)D deficiency (67%). Subjects with 25(OH)D deficiency had highest BMI ( p < 0.001). Stratifying the sample population according to the BMI classes, 25(OH)D levels decreased significantly along with the increase in BMI ( p < 0.001), with the lowest 25(OH)D levels in the class III obesity. In addition, stratifying the sample population according to 25(OH)D categories, BMI and fat mass (FM) decreased, while PhA increased significantly along with the 25(OH)D categories ( p < 0.001). The 25(OH)D levels showed significant positive associations with PhA ( r = -0.59, p < 0.001), and this association remained significant also after adjusting for BMI and FM ( r = 0.60, p < 0.001). The lowest values of PhA were significantly associated with the severity of obesity (OR 0.3, p < 0.001) and of 25(OH)D deficiency (OR 0.2, p < 0.001). To compare the relative predictive power of body composition parameters associated with the 25(OH)D levels, we performed a multiple linear regression analysis. The most sensitive and specific cut-off for 25(OH)D levels to predict the PhA above the median was >14 ng/mL ( p < 0.001). In conclusion, we provided preliminary insights into a novel link between 25(OH)D levels and PhA in the setting of obesity. This association uncovered a new potential usefulness of PhA as expression of cell membrane integrity and predictor of inflammation in low 25(OH)D status that might help in identifying high-risk patients with obesity who could benefit from careful 25(OH)D supplementation., Competing Interests: The authors declare no conflict of interest.

A Vitamin D deficiency and obesity are two public health problems extensively exacerbated over the last years. Among the several mechanisms proposed to account for the complex interplay between vitamin D and obesity, one that has gained particular attention is related to the emerging role of obesity-related changes in gut microbiota and gut-derived metabolites, such as Trimethylamine-N-oxide (TMAO). Vitamin D deficiency and high circulating TMAO levels are associated with body weight and the severity of non-alcoholic fatty liver disease (NAFLD). Considering the link of obesity with vitamin D on the one hand and obesity with TMAO on the other hand, and the central role of the liver in both the vitamin D and TMAO metabolism, the aim of this cross-sectional observational study was first, to confirm the possible inverse association between vitamin D and TMAO across different body mass index (BMI) classes and second, to investigate if this association could be influenced by the presence of NAFLD. One hundred and four adult subjects (50 males and 54 females; 35.38 ± 7.49 years) were enrolled. The fatty liver index (FLI) was used as a proxy for the diagnosis of NAFLD. Vitamin D deficiency was found in 65 participants (62.5%), while 33 subjects (31.7%) had insufficient levels, and the remaining subjects had sufficient levels of vitamin D. Subjects with both vitamin D deficiency and FLI-NAFLD had the highest TMAO levels ( bstract: < 0.001). By stratifying the sample population according to the BMI classes, vitamin D levels decreased significantly along with the increase of plasma TMAO concentrations, with the lowest vitamin D levels and highest TMAO, respectively, in class III obesity. Vitamin D levels showed significant opposite associations with circulating levels of TMAO ( p < 0.001). By stratifying the sample population according to the BMI classes, vitamin D levels decreased significantly along with the increase of plasma TMAO concentrations, with the lowest vitamin D levels and highest TMAO, respectively, in class III obesity. Vitamin D levels showed significant opposite associations with circulating levels of TMAO ( r < 0.001), but this association was no longer significant after the adjustment for FLI values. The highest values of TMAO were significantly associated with the severity of obesity (OR 7.92; p < 0.001), but this association was no longer significant after the adjustment for FLI values. The highest values of TMAO were significantly associated with the severity of obesity (OR 7.92; p < 0.001), deficiency of vitamin D (OR 1.62; p < 0.001), and FLI-NAFLD (OR 3.79; p < 0.001). In conclusion, our study suggests that high TMAO levels are associated with vitamin D deficiency and NAFLD. Further studies are required to investigate if there is a causality link or whether all of them are simply the consequence of obesity.p < 0.001). In conclusion, our study suggests that high TMAO levels are associated with vitamin D deficiency and NAFLD. Further studies are required to investigate if there is a causality link or whether all of them are simply the consequence of obesity., Competing Interests: The authors declare no conflict of interest.

Four new medicines-liraglutide, lorcaserin, bupropion/naltrexone, and phentermine/topiramate-have been recently added to the pharmacological arsenal for obesity treatment and could represent important tools to manage this epidemic disease. To achieve satisfactory anti-obesity goals, the use of these new medicines should be optimized and tailored to specific patient subpopulations also by applying dose adjustments if needed. In the present review, we posit that gender could be among the factors influencing the activity of the new obesity drugs both because of pharmacokinetic and pharmacodynamic factors. Although evidence from premarketing clinical studies suggested that no dose adjustment by gender is necessary for any of these new medicines, these studies were not specifically designed to identify gender-related differences. This observation, together with the strong theoretical background supporting the hypothesis of a gender-dimorphic response, strongly call upon an urgent need of new real-life data on gender-related difference in the pharmacology of these new obesity drugs., (© 2018 World Obesity Federation.)

Epidemiological studies suggested an association between obesity and sleep disturbances. Obstructive sleep apnea is the most prevalent type of obesity-related sleep disorder that lead to an increased risk for numerous chronic health conditions. In addition the increased visceral adipose tissue might be responsible for the secretion of inflammatory cytokines that could contribute to alter the sleep-wake rhythm. Unhealthy food characterized by high consumption of fat and carbohydrate seems to negatively influence the quality of sleep while diet rich of fiber is associated to more restorative and deeper sleep. Although obesity could cause through several pathogenetic mechanisms an alteration of sleep, it has been reported that subjects suffering from sleep disorders are more prone to develop obesity. Experimental laboratory studies have demonstrated that decreasing either the amount or quality of sleep increase the risk of developing obesity. Experimental sleep restriction also causes physiological, hormonal and food behavioral changes that promote a positive energy balance and a compensatory disproportionate increase in food intake, decrease in physical activity, and weight gain. Thus, the aim of this review is to provide observational evidence on the association of obesity with sleep disturbances and viceversa with emphasis on possible pathophysiological mechanisms (hormonal and metabolic) that link these two pathological conditions.

There is raising evidence reporting an increased incidence of breast cancer over the past decades. Every year approximately 1.4 million new cases of breast cancer are diagnosed worldwide, with a mortality rate of approximately 450,000/year. Out of these cases, 6.6% are diagnosed in premenopausal women with a median age at diagnosis of 40 years: in premenopausal women breast cancer seems to be more aggressive than in post-menopausal women. Obesity has been reported to increase the risk of developing breast cancer and to worsen the prognosis. This seems to be due to several obesity-related mechanisms. Insulin resistance that often occurs with obesity may results in compensatory hyperinsulinemia. Insulin cross-binds insulin-like growth factor-I receptors expressed on breast cells, resulting in proliferative stimuli on breast cancer cells. Besides, hyperinsulinemia up-regulates the growth hormone receptor (GHR) thus increasing GHR stimulation and resulting in an increased hepatic IGF-I synthesis. Moreover, insulin decreases the hepatic expression of binding proteins of IGF-I, such as insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-2, thus leading to high circulating and bioavailable free IGF-I. Additionally, obesity is associated to chronic low-grade inflammation that has been reported to be an additional stimulus for tumor growth. This review shows the current evidence regarding to the association of obesity and breast cancer in premenopausal state focusing on both human and basic studies; showing that the obesity is a risk factor for breast cancer also among premenopausal women, especially for the molecular subtype Triple Negative Breast Cancer., (Copyright © 2018. Published by Elsevier B.V.)

Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products. The window of life during which the exposure happens could lead to different effects. A critical window is during utero and/or neonatal period in which the obesogens could cause subtle changes in gene expression and tissue organization or blunt other levels of biological organization leading to increased susceptibility to diseases in the adulthood. Some of the reasons for this increased sensitivity include the lack of the protective mechanisms that are available in adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism and the blood/brain barrier still not fully functional in the fetus or newborn. The mechanisms of action of obesogens lay on their ability to increase the number and/or the size of the adipocytes and to alter appetite, satiety and food preferences. The ability of obesogens to increase fat deposition results in an increased capacity for their own retention due to their lipophilic properties; thus prolonging the exposure and increasing the detrimental metabolic consequences.

The aim of this review is to provide a general overview of the possible associations among the vitamin D status, air pollution and obesity. Sunlight exposure accounts in humans for more than 90 % of the production of vitamin D. Among emerging factors influencing sunlight-induced synthesis of vitamin D, prospective and observational studies proved that air pollution constitutes an independent risk factor in the pathogenesis of vitamin D hypovitaminosis. In addition, environmental pollutants can affect risk of obesity when inhaled, in combination with unhealthy diet and lifestyle. In turn, obesity is closely associated with a low vitamin D status and many possible mechanisms have been proposed to explain this association. The associations of air pollution with low vitamin D status on the hand and with obesity on the other hand, could provide a rationale for considering obesity as a further link between air pollution and low vitamin D status. In this respect, a vicious cycle could operate among low vitamin D status, air pollution, and obesity, with additive detrimental effects on cardio-metabolic risk in obese individuals. Besides vitamin D supplementation, nutrient combination, used to maximize the protective effects against air pollution, might also contribute to improve the vitamin D status by attenuating the "obesogen" effects of air pollution.

Low vitamin D status and obesity have concomitantly reached epidemic levels worldwide. Up to now the direction of the association between low vitamin D status and obesity, the exact mechanisms responsible for this association and the clinical usefulness to increase vitamin D status for reducing adiposity still warrant further evaluation. The aim of the present review was to examine the current evidence linking low vitamin D status and obesity in relation to the role of the nutritionist. On the one side, considering obesity as a causal factor, low sun exposure in obese individuals due to their sedentary lifestyle and less outdoor activity, vitamin D sequestration in adipose tissue, and volumetric dilution of ingested or cutaneously synthesized vitamin D 3 in the large fat mass of obese patients, might represent some of the factors playing a major role in the pathogenesis of the low vitamin D status. On the other side, the expression of both vitamin D 3 receptors and enzymes responsible for vitamin D 3 metabolism in adipocytes depicted a role for the low vitamin D status per se in the development of obesity by modulating adipocyte differentiation and lipid metabolism. Nutritionists need to accurately address the aspects influencing the low vitamin D status in obesity and the vitamin D supplementation in obese individuals.

Objectives: Investigate the prevalence of obesity in Italy and examine its resource consumption and economic impact on the Italian national healthcare system (NHS)., Design: Retrospective, observational and real-life study., Setting: Data from three health units from Northern (Bergamo, Lombardy), Central (Grosseto, Tuscany) and Southern (Naples, Campania) Italy., Participants: All patients aged ≥18 years with at least one recorded body mass index (BMI) measurement between 1 January 2009 and 31 December 2012 were included., Interventions: Information retrieved from the databases included primary care data, medical prescriptions, specialist consultations and hospital discharge records from 2009-2013. Costs associated with these data were also calculated. Data are presented for two time periods (1 year after BMI measurement and study end)., Primary and Secondary Outcome Measures: Primary-to estimate health resources consumption and the associated economic impact on the Italian NHS. Secondary-the prevalence and characteristics of subjects by BMI category., Results: 20 159 adult subjects with at least one documented BMI measurement. Subjects with BMI ≥30 kg/m 2 were defined as obese. The prevalence of obesity was 22.2% (N=4471) and increased with age. At the 1-year observation period, obese subjects who did not receive treatment for their obesity experienced longer durations of hospitalisation (median length: 5 days vs 3 days), used more prescription drugs (75.0% vs 57.7%), required more specialised outpatient healthcare (mean number: 5.3 vs 4.4) and were associated with greater costs, primarily owing to prescription drugs and hospital admissions (mean annual cost per year per patient: €460.6 vs €288.0 for drug prescriptions, €422.7 vs € 279.2 for hospitalisations and €283.2 vs €251.7 for outpatient care), compared with normal weight subjects. Similar findings were observed for the period up to data cut-off (mean follow-up of 2.7 years)., Conclusions: Untreated obesity has a significant economic impact on the Italian healthcare system, highlighting the need to raise awareness and proactively treat obese subjects., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: This study was aimed at evaluating sirtuin 4 (Sirt4) levels in obese individuals, in relation to their adherence to the Mediterranean diet (MD), a healthy dietary pattern characterized by high antioxidant capacity, and markers of visceral fat storage., Subjects/methods: Forty-three obese patients (44% males; BMI: 36.7-58.8 kg/m 2 ) were consecutively included. PREvención con DIeta MEDiterránea (PREDIMED) and the 7-day food records were used to assess the adherence to MD and dietary pattern, respectively. Visceral adiposity index (VAI) was calculated. Sirt4 levels were detected by ELISA method., Results: The majority of the obese participants (62.8%) had an average adherence to MD. Compared with average adherers, low adherers had higher BMI, energy intake, and percentage of energy from lipids, mainly saturated fat and polyunsaturated fatty acids (PUFA), and lower Sirt4 levels. After adjusting for BMI, Sirt4 levels remained negatively correlated with VAI. After adjusting for total energy intake, Sirt4 levels remained negatively associated with PREDIMED and consumption of n-3 PUFA, vitamins C and E. The threshold value of PREDIMED predicting the lowest decrease in Sirt4 levels was found at a score of 6., Conclusions: Less reduced Sirt4 levels in obese patients adhering to MD suggest a further aspect of the antioxidant advantage of MD.

Adulthood and childhood obesity is rapidly becoming an epidemic problem and it has a short and long-term impact on health. Short-term consequences are mostly represented by psychological effects; in fact obese children have more chances to develop psychological or psychiatric problems than non-obese children. The main long-term effect is represented by the fact that childhood obesity continues into adulthood obesity and this results in negative effects in young adult life, since obesity increases the risk to develop morbidity and premature mortality. The obesity-related diseases are mostly represented by hypertension, type 2 diabetes, dyslipidemia, cardiovascular diseases. Medical treatment should be discouraged in childhood because of the side effects and it should be only reserved for obese children with related medical complications. Lifestyle changes should be encouraged in both adulthood and childhood obesity. This review focuses on the management of obesity both in adulthood and in childhood, paying particular attention to lifestyle changes that should be recommended.

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity.

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Despite the considerable body of evidence pointing to a possible relationship between the state of the adipose tissue depots and regulation of the somatotropic axis, to date the relationship between obesity and low growth hormone (GH) status remains incompletely understood. The low GH status in obesity is mainly considered as a functional condition, largely reversible after a sustained weight loss. Moreover, due to the effects of the adiposity on the regulation of the somatotropic axis, the application of GH stimulation tests in obesity may also lead to an incorrect diagnosis of GH deficieny (GHD). On the other hand, similar to patients with GHD unrelated to obesity, the reduced GH response to stimulation testing in obese individuals is associated with increased prevalence of cardiovascular risk factors and detrimental alterations of body composition, which contribute to worsening their cardio-metabolic risk profile. In addition, the reduced GH secretion may result in reduced serum insulin-like growth factor (IGF)-1 levels, and the concordance of low peak GH and low IGF-1 identifies a subset of obese individuals with high cardiovascular risk. Furthermore, after weight loss, the normalization of the GH response and IGF-1 levels may or may not occur, and in patients undergoing bariatric surgery the persistence of a low GH status may affect the post-operative outcomes. In this review, we will provide an overview on some clinically relevant aspects of the relationship between obesity axis and the somatotropic axis in the light of the recently published research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present study shows low circulating levels of SIRT4 in obese patients with nonalcoholic fatty liver disease mirroring its reduced mitochondrial expression in an attempt to increase the fat oxidative capacity and then the mitochondrial function in liver and in muscle. SIRT4 modulates the metabolism of free fatty acids reducing their high circulating levels but, unfortunately, increasing ROS production. Great concentration of free fatty acids, released by adipose tissue, coupled with oxidative stress, directly results in endothelial dysfunction, early atherosclerosis, and coronary artery disease risk factor.

Aim: To investigate the weight loss and glycemic control status [blood glucose, hemoglobin A1c (HbA1c) and hypoglycaemic treatment]., Methods: The primary risk factor for type 2 diabetes is obesity, and 90% of all patients with type 2 diabetes are overweight or obese. Although a remarkable effect of bariatric surgery is the profound and durable resolution of type 2 diabetes clinical manifestations, little is known about the difference among various weight loss surgical procedures on diabetes remission. Data from patients referred during a 3-year period (from January 2009 to December 2011) to the University of Naples "Federico II" diagnosed with obesity and diabetes were retrieved from a prospective database. The patients were split into two groups according to the surgical intervention performed [sleeve gastrectomy (SG) and mini-gastric bypass (MGB)]. Weight loss and glycemic control status (blood glucose, HbA1c and hypoglycaemic treatment) were evaluated., Results: A total of 53 subjects who underwent sleeve gastrectomy or mini-gastric bypass for obesity and diabetes were screened for the inclusion in this study. Of these, 4 subjects were excluded because of surgical complications, 7 subjects were omitted because young surgeons conducted the operations and 11 subjects were removed because of the lack of follow-up. Thirty-one obese patients were recruited for this study. A total of 15 subjects underwent SG (48.4%), and 16 underwent MGB (51.6%). After adjusting for various clinical and demographic characteristics in a multivariate logistic regression analysis, high hemoglobin A1c was determined to be a negative predictor of diabetes remission at 12 mo (OR = 0.366, 95%CI: 0.152-0.884). Using the same regression model, MGB showed a clear trend toward higher diabetes remission rates relative to SG (OR = 3.780, 95%CI: 0.961-14.872)., Conclusion: Although our results are encouraging regarding the effectiveness of mini-gastric bypass on diabetes remission, further studies are needed to provide definitive conclusions in selecting the ideal procedure for diabetes remission.

Background: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The IGF-I system is deregulated in obese subjects in proportion to their degree of visceral adiposity., Aim: To examine the association among IGF-I, IGF-binding protein (BP)-1 and -3 levels and different measures of adiposity in a sample of adult male population in Southern Italy., Materials and Methods: A complete database for this analysis was available for 229 (age range 50-82 yr) participating at 2002-2004 Olivetti Heart Study follow-up., Results: After adjustment for age, IGF-I was inversely associated with body mass index (BMI) and waist circumference (p<0.05). IGFBP-1 was inversely associated with BMI, waist circumference, SST, homeostasis model assessment (HOMA) index, fat mass. HOMA index, age, and SST significantly predicted the IGFBP-1 plasma levels, with 24% of IGFBP-1 variability explained at a linear regression analysis., Conclusions: IGFBP-1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFBP-1 levels. The evaluation of some components of the IGF system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults.

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 (β = 0.50, p < 0.0001, β = 0.30, p = 0.01 and β = 0.18, p = 0.048 respectively, while the severity of HS was predicted by visceral and subcutaneous adiposity and HOMA (β = 0.50, p < 0.0001 and β = 0.27, p = 0.001 and β = 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.

Aim: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH)., Methods: Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT) strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls., Results: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008). γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations., Conclusion: MUOs could be detected by Bcl-2 levels. By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.

Background: Fat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS., Methods: The study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound., Results: Metabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (β = -0.49; p = 0.001) and IGFBP-1 (β = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (β = -0.43; p = 0.004)., Conclusions: The present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.

The synthesis of serotonin at CNS level is influenced by diet. Moreover, insulin resistance is associated with lower serotonin levels. Visceral obesity, strictly linked to hepatic steatosis is specifically associated with mild to severe somatic affective-depressive symptom clusters. Previous data support the view that depression involves serotonergic systems, reflecting low levels of urinary 5- hydroxy-3-indoleacetic acid (5-HIAA). The 24-h urinary excretion of 5-HIAA was evaluated in 76 dystimic/depressed, obese/overweight females, divided into two groups, i.e., on a hyper-caloric diet, associated with a life style characterized by leisure time sedentary behavior (LTSB, 35 women), or on a normo-caloric diet, assisted by program-based strategies aimed at promoting physical activity participation (PAP, 41 women). Beck Depression Inventory (BDI) was carried out to score the severity of dystimia/depression. Anthropometric measures, metabolic indices, severity of hepatic steatosis at sonography and HOMA were studied. Urinary levels of 5-HIAA in controls and PAP groups were comparable with a great overlap, while in the LTSB group the urinary excretion of 5-HIAA was significantly reduced in respect to that of the PAP group and obviously compared to that of the control group, 3.4±1.4 mg/L versus 6.2±2.7 mg/L and 6.4±2.6 mg/L, respectively, ANOVA test, P= 0.001. Among metabolic indices, cholesterol, HDL-cholesterol, triglycerides and uric acid were not able to predict urinary concentrations of 5-HIAA, which were not associated with hepatic steatosis; vice versa, ferritin levels, and mainly HOMA values, were independent predictors of the urinary excretion of 5-HIAA (β=0.235 and 0.45, respectively). Dystimia/depression severity was negatively predicted by urinary 5-HIAA levels in the sense that the highest BDI values were forecast by the lowest values of urinary 5-HIAA (β= -0.72).The importance of measuring the 24-h urinary excretion of 5-HIAA in follow-ups could rely on a method simultaneously mirroring the well-being status, the adherence to physical activity, which leads to improved insulin sensitivity, and the eating habits acquired by dystimic/depressed overweight/obese patients. In contrast, the significance of the urinary 5-HIAA is reduced in evaluating the severity of hepatic steatosis, likely because it is a structured process.

Aim: Obesity is associated with an altered GH/IGF-I axis status, accounting for the increased cardiovascular risk in obese subjects with GH deficiency. Aim of this randomized, simple-blind, cross-over study was to verify the effectiveness of a short-term treatment with orlistat in reducing non-esterified fatty acid (NEFA) and influencing the endogenous activity of GH/IGF-I axis in obese subjects., Outcome Measures: The primary outcome measures were post-prandial lipemia; GH peak after GHRH+arginine; IGF-I; IGF-binding protein (BP)-3, IGF-I/IGFBP-3 ratio. Secondary outcome measures were insulin resistance (IR) indexes (homeostasis model assessment of insulin resistance and Insulin Sensitivity Index)., Study Design: Twenty obese post-menopausal women (age: 53.6 ± 6.2; body mass index: 34.1 ± 4.0) were randomized to receive normo-caloric diet plus + orlistat (Roche, UK; 120 mg tid) or normo-caloric diet without the additional treatment. The duration of follow-up was 10 days for each treatment period., Results: Orlistat induced a weight-independent reduction in post-prandial NEFA levels compared with diet alone, with higher GH peak, IGF-I, and IGF-I/IGFBP3 ratio. GH peak was correlated negatively with postprandial NEFA and positively with IGF-I and IGF-I/IGFBP-3 ratio., Conclusions: Orlistat is effective in inducing a weight-independent higher reduction in post-prandial NEFA levels than dietary treatment alone along with increase in GH peak, IGF-I levels, and IGFI/ IGFBP-3 ratio. These results might add a new potential benefit of orlistat in the management of obese subjects.

Non-alcoholic fatty liver disease, characterized by hepatocyte apoptosis, is distinct in fatty liver and non-alcoholic steatohepatitis, the more severe form. Apoptotic cell death is caspase-dependent and associated with mitochondrial membrane depolarization and cytochrome c release. Adhering to the hypothesis that the exposure of hepatocytes to free fatty acids, resulting in increased ROS production and mitochondrial damage, is balanced by the presence of antioxidant substances, circulating levels of gamma-glutamyl transferase, cytochrome c, triglycerides and unconjugated bilirubin were explored in patients suffering from non-alcoholic fatty liver disease with different severity. One hundred and eighty-six consecutive patients who presented recent ultrasound feature of bright liver without any liver disease of known origin were enrolled, eighty-nine of whom underwent liver biopsy. Forty-five subjects were allocated on the basis of histology in fatty liver group while 44 patients formed the group with non-alcoholic steatohepatitis. A cohort of 27 young, lean, apparently healthy individuals was selected as control group. The levels of gamma-glutamyl transferase were normal or slightly increased, while unconjugated bilirubin concentrations were elevated in all the spectra of non-alcoholic fatty liver disease. Comparing the present results with relevant findings from other studies dealing with diseases characterized by apoptosis, we did not find high circulating levels of cytochrome c in non-alcoholic fatty liver disease. What is more, our patients, categorized as suffering from simple fatty liver or from the more severe non-alcoholic steatohepatitis, had similar levels of cytochrome c and gamma-glutamyl transferase, p=0.19 and 0.11. Serum triglycerides were higher in patients with non-alcoholic fatty liver disease than in the healthy group, p=0.001. These findings likely reflect a balance between oxidative stress and anti-oxidant response rather than a lack of reliability of cytochrome c as a reliable biomarker of mitochondrial damage.

Background and Aim: There is a considerable heterogeneity in metabolic phenotype among equally obese subjects. Impaired GH secretion is frequent in obese patients, with GH secretion reduced up to levels that are comparable to those found in adult patients with organic GH deficiency (GHD). Low GH status exerts detrimental effects onmetabolic abnormalities in organic GHD patients. The aim of this observational, retrospective study was to investigate the prevalence of the metabolic syndrome (MetS) in moderately-severely obese subjects who met criteria for GDH (GHD) and in those with normal GH status (GH sufficient: GHS)., Methods and Results: One-hundred and ninety-five moderately-severely obese individuals partecipated, 149 women and 46 males [bodymass index (BMI) 43.0+/-4.4 kg/m2 aged 34.3+/-11.8 yr] . Main outcome measures were: GH peak after GHRH plus arginine test, IGF-I, MetS parameters according to National Cholesterol Education Program criteria. Fifty-five subjects (27.3%) were GHD (49 females and 6 males). The prevalence of MetS parameters was 70.9% in GHD subgroup vs 52.9% in GHS (chi2=5.281; p=0.02) and the likelihood of MetS was highest in GHD subgroup (odds ratio: 2.174; 95% confidence interval 1.113 to 4.248). At the multiple regression analysis either GH peak or IGF-I were the major determinants of waist circumference (beta=-0.380, t=-6.110 and beta=-0.326, t=-4.704, respectively; p<0.001), while age and IGFI were the major determinants of MetS (beta=0.255, t= 3.342, and beta=-0.282, t=-3.270; p=0.02, respectively)., Conclusions: Among moderately-severely obese individuals the prevalence of the MetS was higher in GHD than in GHS subjects. Thus, in obese subjects, GH status investigation might be considered in the clinical evaluation of their metabolic risk profile.

Aim: To identify which parameters could help to distinguish the "metabolically benign obesity", which is not accompanied by insulin resistance (IR) and early atherosclerosis., Methods: Eighty two of 124 overweight/obese females formed the study population, which was divided into two groups (52 and 30 subjects, respectively) with and without IR according to a HO meostatic Metabolic Assessment (HOMA) cut-off of 2, and were studied in a cross-sectional manner. The main outcome measures were waist circumference, serum uric acid, high-density lipoprotein-cholesterol and triglycerides, alanine aminotransferase, blood pressure and the two imaging parameters, hepatic steatosis and longitudinal diameter of the spleen, which were measured in relation to the presence/absence of IR., Results: A variable grade of visceral obesity was observed in all subjects with the exception of three. Obesity of a severe grade was represented more in the group of IR individuals (P = 0.01). Hepatic steatosis, revealed at ultrasound, was more pronounced in IR than in non-IR subjects (P = 0.005). The two groups also demonstrated a clear difference in longitudinal spleen diameter and blood pressure, with raised and significant values in the IR group. Metabolic syndrome was frequent in the IR group, and was not modified when adjusted for menopause (P = 0.001). At linear regression, the beta values of waist circumference and body mass index predicting HOMA were 0.295, P = 0.007 and 0.41, P = 0.0001, respectively. Measures of spleen longitudinal diameter were well predicted by body mass index (BMI) values, beta = 0.35, P = 0.01, and by HOMA, beta = 0.41, P = 0.0001. Blood pressure was predicted by HOMA values, beta = 0.39, P = 0.0001). HOMA and hepatic steatosis were highly associated (rho = 0.34, P = 0.002). Interestingly, IR patients were almost twice as likely to have hepatic steatosis as non-IR patients. Among the MS criteria, blood pressure was very accurate in identifying the presence of IR (AUROC for systolic blood pressure 0.66, cut-off 125 mm of Hg, sensibility 64%, specificity 75%; AUROC for diastolic blood pressure 0.70, cut-off 85 mm of Hg, sensibility 54.5%, specificity 75%)., Conclusion: As health care costs are skyrocketing, reliable and mainly inexpensive tools are advisable to better define subjects who really need to lose weight.

There is increasing interest in the use of bariatric surgery to achieve weight loss in individuals with severe obesity. However, there are concerns over the loss of lean body mass (LBM) following surgery in individuals who have functional growth hormone (GH) deficiency related to their obesity. We discuss here the results of an open-label study in which we studied the efficacy of GH treatment to prevent loss of LBM and metabolic disturbances in 24 women with functional severe GH deficiency who were undergoing laparoscopic adjustable gastric banding for severe obesity. Participants were randomized to standard care (including a dietary restriction programme) with or without GH treatment, and were studied for 6 months. Overall, weight loss and reductions in waist circumference were similar in the two groups. GH treatment was associated with a significant decrease in fat mass and a significantly smaller decrease in LBM, as well as improvements in insulin sensitivity, and lipid profile.