'Obesities': Position statement on a complex disease entity with multifaceted drivers.

Academic medicine fosters research that moves from discovery to translation, at the same time as promoting education of the next generation of professionals. In the field of obesity, the supposed integration of knowledge, discovery and translation research to clinical care is being particularly hampered. The classification of obesity based on the body mass index does not account for several subtypes of obesity. The lack of a universally shared definition of "obesities" makes it impossible to establish the real burden of the different obesity phenotypes. The individual's genotype, adipotype, enterotype and microbiota interplays with macronutrient intake, appetite, metabolism and thermogenesis. Further investigations based on the concept of differently diagnosed "obesities" are required.

The Influence of Personality Traits on Emotion Expression in Bulimic Spectrum Disorders: A Pilot Study.

Facial expressions are critical in forming social bonds and in signalling one's emotional state to others. In eating disorder patients, impairments in facial emotion recognition have been associated with eating psychopathology severity. Little research however has been carried out on how bulimic spectrum disorder (BSD) patients spontaneously express emotions. Our aim was to investigate emotion expression in BSD patients and to explore the influence of personality traits. Our study comprised 28 BSD women and 15 healthy controls. Facial expressions were recorded while participants played a serious video game. Expressions of anger and joy were used as outcome measures. Overall, BSD participants displayed less facial expressiveness than controls. Among BSD women, expressions of joy were positively associated with reward dependence, novelty seeking and self-directedness, whereas expressions of anger were associated with lower self-directedness. Our findings suggest that specific personality traits are associated with altered emotion facial expression in patients with BSD. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Regulation of adipocyte lipolysis.

In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under fasting conditions or times of elevated energy demands is tightly regulated by neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among the classic regulators of lipolysis, adrenergic stimulation and the insulin-mediated control of lipid mobilisation are the best known. Initially, hormone-sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for lipolysis initiation. Pivotal, previously unsuspected components have also been identified at the protective interface of the lipid droplet surface and in the signalling pathways that control lipolysis. Perilipin, comparative gene identification-58 (CGI-58) and other proteins of the lipid droplet surface are currently known to be key regulators of the lipolytic machinery, protecting or exposing the TAG core of the droplet to lipases. The neuroendocrine control of lipolysis is prototypically exerted by catecholaminergic stimulation and insulin-induced suppression, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent decades adipose tissue has been shown to secrete a large number of adipokines, which exert direct effects on lipolysis, while adipocytes reportedly express a wide range of receptors for signals involved in lipid mobilisation. Recently recognised mediators of lipolysis include some adipokines, structural membrane proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen-activated protein kinase. Lipolysis needs to be reanalysed from the broader perspective of its specific physiological or pathological context since basal or stimulated lipolytic rates occur under diverse conditions and by different mechanisms.

Targeting the circulating microRNA signature of obesity.

BACKGROUND: Genomic studies have yielded important insights into the pathogenesis of obesity. Circulating microRNAs (miRNAs) are valuable biomarkers of systemic diseases and potential therapeutic targets. We sought to define the circulating pattern of miRNAs in obesity and examine changes after weight loss. METHODS: We assessed the genomewide circulating miRNA profile cross-sectionally in 32 men and after surgery-induced weight loss in 6 morbidly obese patients. The most relevant miRNAs were cross-sectionally validated in 80 men and longitudinally in 22 patients (after surgery-induced weight loss). We evaluated the effects of diet-induced weight loss in 9 obese patients. Thirty-six circulating miRNAs were associated with anthropometric variables in the initial sample. RESULTS: In the validation study, morbidly obese patients showed a marked increase of miR-140-5p, miR-142-3p (both P < 0.0001), and miR-222 (P = 0.0002) and decreased levels of miR-532-5p, miR-125b, miR-130b, miR-221, miR-15a, miR-423-5p, and miR-520c-3p (P < 0.0001 for all). Interestingly, in silico targets leukemia inhibitory factor receptor (LIFR) and transforming growth factor receptor (TGFR) of miR-140-5p, miR-142-3p, miR-15a, and miR-520c-3p circulated in association with their corresponding miRNAs. Moreover, a discriminant function of 3 miRNAs (miR-15a, miR-520c-3p, and miR-423-5p) was specific for morbid obesity, with an accuracy of 93.5%. Surgery-induced (but not diet-induced) weight loss led to a marked decrease of miR-140-5p, miR-122, miR-193a-5p, and miR-16-1 and upregulation of miR-221 and miR-199a-3p (P < 0.0001 for all). CONCLUSIONS: Circulating miRNAs are deregulated in severe obesity. Weight loss-induced changes in this profile and the study of in silico targets support this observation and suggest a potential mechanistic relevance.

Dynamic fronto-amygdalar interactions underlying emotion-regulation deficits in women at higher weight.

OBJECTIVE: The regulation of negative emotions entails the modulation of subcortical regions, such as the amygdala, by prefrontal regions. There is preliminary evidence suggesting that individuals at higher weight may present with hypoactivity in prefrontal regulatory systems during emotional regulation, although the directionality of these pathways has not been tested. In this study, we compared fronto-amygdalar effective connectivity during cognitive reappraisal as a function of BMI in 48 adult women with obesity and 54 control participants. METHODS: Dynamic causal modeling and parametric empirical Bayes were used to map effective connectivity between the dorsomedial prefrontal cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and the amygdala. RESULTS: Difficulty in Emotion Regulation Scale scores were higher in the obesity group compared with control participants (p < 0.001). A top-down cortical model best explained our functional magnetic resonance imaging data (posterior probability = 86%). Participants at higher BMI were less effective at inhibiting activity in the amygdala via the orbitofrontal cortex and dorsomedial prefrontal cortex during reappraisal compared with those at lower BMI. In contrast, increased excitatory modulation of dorsolateral prefrontal cortex-to-amygdalar connectivity was found in participants at lower BMI. CONCLUSIONS: These findings support a framework involving alterations in fronto-amygdalar connectivity contributing to difficulties in regulating negative affect in individuals at higher weight.

Time to Consider the "Exposome Hypothesis" in the Development of the Obesity Pandemic.

The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent the main contributors to the obesity problem, they are not able to fully explain all cases and current trends. In this context, a body of knowledge related to exposure to as yet underappreciated obesogenic factors, which can be referred to as the "exposome", merits detailed analysis. Contrarily to the genome, the "exposome" is subject to a great dynamism and variability, which unfolds throughout the individual's lifetime. The development of precise ways of capturing the full exposure spectrum of a person is extraordinarily demanding. Data derived from epidemiological studies linking excess weight with elevated ambient temperatures, in utero, and intergenerational effects as well as epigenetics, microorganisms, microbiota, sleep curtailment, and endocrine disruptors, among others, suggests the possibility that they may work alone or synergistically as several alternative putative contributors to this global epidemic. This narrative review reports the available evidence on as yet underappreciated drivers of the obesity epidemic. Broadly based interventions are needed to better identify these drivers at the same time as stimulating reflection on the potential relevance of the "exposome" in the development and perpetuation of the obesity epidemic.

Clinical and Neurophysiological Correlates of Emotion and Food Craving Regulation in Patients with Anorexia Nervosa.

BACKGROUND: Difficulties in emotion regulation and craving regulation have been linked to eating symptomatology in patients with anorexia nervosa (AN), contributing to the maintenance of their eating disorder. METHODS: To investigate clinical and electrophysiological correlates of these processes, 20 patients with AN and 20 healthy controls (HC) completed a computerized task during EEG recording, where they were instructed to down-regulate negative emotions or food craving. Participants also completed self-report measures of emotional regulation and food addiction. The P300 and Late Positive Potential (LPP) ERPs were analysed. RESULTS: LPP amplitudes were significantly smaller during down-regulation of food craving among both groups. Independent of task condition, individuals with AN showed smaller P300 amplitudes compared to HC. Among HC, the self-reported use of re-appraisal strategies positively correlated with LPP amplitudes during emotional regulation task, while suppressive strategies negatively correlated with LPP amplitudes. The AN group, in comparison to the HC group, exhibited greater food addiction, greater use of maladaptive strategies, and emotional dysregulation. CONCLUSIONS: Despite the enhanced self-reported psychopathology among AN, both groups indicated neurophysiological evidence of food craving regulation as evidenced by blunted LPP amplitudes in the relevant task condition. Further research is required to delineate the mechanisms associated with reduced overall P300 amplitudes among individuals with AN.

High cotinine levels are persistent during the first days of life in newborn second hand smokers.

BACKGROUND: Despite the adverse effects of maternal smoking during pregnancy on the newborn's health are well-known, in the pediatric population, a high prevalence exists that is very much affected by second hand smoke (SHS). This study aims to investigate the impact of maternal smoking habits during pregnancy on cotinine levels in newborns during the first days of life. The high association between cotinine concentration in maternal and umbilical cord blood (UCB) has been previously reported, but the levels of blood cotinine that remain in infants born to smokers is unknown. METHODS: Cotinine concentration was measured in UCB, in maternal and newborn peripheral blood. Data from UCB sample dyads of ninety mothers and from seventy-one newborns were analyzed. RESULTS: Cotinine levels were significantly different among non-smokers (9.9 ± 5.9 ng/ml), moderate (67.3 ± 7.4 ng/ml), and heavy smokers (137.7 ± 19.5 ng/ml) (p<0.0001). Significant correlations were found between maternal and UCB cotinine (r=0.748; p<0.001), and between UCB and newborn plasma cotinine at 48 h after birth (r=0.541; p<0.001). The smokers exposed their infants to cotinine with a median of 31.7 ± 8.6 ng/ml (moderate) or 59.1 ± 13.3 ng/ml (heavy smokers) until at least, 48 h after birth. Reduced birth weight and length were significantly related with UCB cotinine levels. CONCLUSIONS: A positive association between UCB and plasmatic cotinine in newborns was found. The high cotinine levels detected in newborns from smoker mothers indicates that their infants are subjected to elevated SHS from birth. These results can help to reinforce the awareness of the adverse effects of smoking during pregnancy.

Explicit and implicit emotional expression in bulimia nervosa in the acute state and after recovery.

Expression of emotional state is considered to be a core facet of an individual's emotional competence. Emotional processing in BN has not been often studied and has not been considered from a broad perspective. This study aimed at examining the implicit and explicit emotional expression in BN patients, in the acute state and after recovery. Sixty-three female participants were included: 22 BN, 22 recovered BN (R-BN), and 19 healthy controls (HC). The clinical cases were drawn from consecutive admissions and diagnosed according to DSM-IV-TR diagnostic criteria. Self reported (explicit) emotional expression was measured with State-Trait Anger Expression Inventory-2, State-Trait Anxiety Inventory, and Symptom Check List-90 items-Revised. Emotional facial expression (implicit) was recorded by means of an integrated camera (by detecting Facial Feature Tracking), during a 20 minutes therapeutic video game. In the acute illness explicit emotional expression [anxiety (p<0.001) and anger (p<0.05)] was increased. In the recovered group this was decreased to an intermediate level between the acute illness and healthy controls [anxiety (p<0.001) and anger (p<0.05)]. In the implicit measurement of emotional expression patients with acute BN expressed more joy (p<0.001) and less anger (p<0.001) than both healthy controls and those in the recovered group. These findings suggest that there are differences in the implicit and explicit emotional processing in BN, which is significantly reduced after recovery, suggesting an improvement in emotional regulation.

Prevalence and factors related to urinary albumin excretion in obese youths.

OBJECTIVES: The aim of the present study is to assess whether obesity is associated with urinary albumin excretion and what the main determinants are. METHODS: One hundred and thirty-four obese white children and adolescents of both sexes, ranging from 9 to 18 years of age (mean age 12.6 ±â€Š2.0), were included in the study. Obesity was defined on the basis of a threshold BMI z-score of more than 2 (Cole's LMS method) and overweight with a BMI from the 85th to 95th percentile. Office blood pressure was measured using a mercury sphygmomanometer. Urinary albumin excretion was measured in the first voiding urine of the morning and expressed in albumin/creatinine ratio in mg/g. Reproducibility of the urinary albumin excretion was studied by the Bland and Altman technique in a subgroup. Triglycerides, uric acid, fasting glucose and insulin were measured and the homeostatic model assessment (HOMA) index was calculated. RESULTS: The prevalence of microalbuminuria was 2.4%. No differences in the prevalence of microalbuminuria were observed when the different groups of obesity degree were compared (0, 2.2 and 0% in overweight, moderate and severe obese, respectively). A significant relationship emerged between the Log urinary albumin excretion and BMI z-score, waist circumference, Log triglycerides, fasting insulin and HOMA index, adjusted by age and sex. In a multiple regression analysis, the main determinants of Log urinary albumin excretion were sex, waist circumference and Log triglycerides. In 17% of the individuals who fulfil criteria for metabolic syndrome, urinary albumin excretion was significantly higher than those without. CONCLUSION: The prevalence of elevated urinary albumin excretion is not prominent in obese children, and when it is increased, it depends mainly on metabolic factors.

Proyectos de investigación en salud del Fondo de Investigaciones Sanitarias 2008: permanencia y adaptación al VI Plan Nacional de Investigación, Desarrollo e Innovación 2008–2011 / The research projects in health of the Spanish Sanitary Research Fund in the year 2008: Accordance to the VI National Plan of R&D 2008-2011

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