Brain dysfunctions, psychopathologies, and body image distortions

The major features in eating disorders are a preoccupation with food and its consumption and body dissatisfaction. Diagnostic manuals provide clusters of criteria according to which affected individuals can be categorized into one or other group of eating disorder. Yet, when considering the high proportion of comorbidities and ignoring the content of the symptoms (food, body), the major features seem to yield obsessional-compulsive, addictive, and impulsive qualities. In the present article, we review studies from the neuroscientific literature (mainly lesion studies) on eating disorder, obsessive-compulsive disorder, impulse control disorder, and addiction to investigate the possibility of a wider phenotype that can be related to a common brain network. The literature localizes this network to the right frontal lobe and its connectivities. This network, when dysfunctional, might result in a behavior that favors the preoccupation with particular thoughts, behaviors, anxieties, and uncontrollable urges that are accompanied by little scope for ongoing behavioral adjustments (e.g., impulse control). We reason that this network may turn out to be equally involved in understudied mental conditions of dysfunctional body processing such as muscle dysmorphia, body dysmorphic disorder (including esthetic surgery), and xelomelia. We finally consider previous notions of a wider phenotype approach to current diagnostic practice (using DSM), such as the possibility of a model with a reduced number of diagnostic categories and primary and secondary factors, and to etiological models of mental health conditions.

Am I shrinking? On clothing size and body size.

Comment on: Hughes LA, Schouten LJ, Goldbohm RA, van den Brandt PA, Weijenberg MP. Self-reported clothing size as a proxy measure for body size. Epidemiology. 2009 Sep;20(5):673-6. PMID: 19451821

Covariation between eumelanic pigmentation and body mass only under specific conditions.

Identifying the factors that mediate covariation between an ornament and other phenotypic attributes is important to determine the signaling function of ornaments. Sign and magnitude of a covariation may vary across environments if the expression of the ornament or of its linked genes regulating correlated phenotypes is condition-dependent. I investigated in the barn owl Tyto alba whether sign and magnitude of covariation between body mass and two heritable melanin-based plumage ornaments change with food supply, along the reproductive cycle and from the morning to the evening. Using a dataset of 1,848 measurements of body mass in 336 breeding females, I found that females displaying large black spots were heavier than conspecifics with smaller spots in the afternoon (i.e., a long time after the last feeding) but not in the morning (i.e., a short time after the last feeding). This is consistent with the recently proposed hypothesis that eumelanin-based ornaments are associated with the ability to maintain energy balance between food intake and energy expenditure. Thus, covariation between melanin-based coloration and body mass can be detected only under specific conditions potentially explaining why it has been reported in only ten out of 28 vertebrate species. The proposition that ornamented individuals achieve a higher fitness than drab conspecifics only in specific environments should be tested for other ornaments.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Beneficial effects of combinatorial micronutrition on body fat and atherosclerosis in mice.

AIMS: More than two billion people worldwide are deficient in key micronutrients. Single micronutrients have been used at high doses to prevent and treat dietary insufficiencies. Yet the impact of combinations of micronutrients in small doses aiming to improve lipid disorders and the corresponding metabolic pathways remains incompletely understood. Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosis in mice. METHODS AND RESULTS: Lipoprotein receptor-null mice fed with an original combination of micronutrients incorporated into the daily chow showed reduced weight gain, body fat, plasma triglycerides, and increased oxygen consumption. These effects were achieved through enhanced lipid utilization and reduced lipid accumulation in metabolic organs and were mediated, in part, by the nuclear receptor PPARα. Moreover, the micronutrients partially prevented atherogenesis when administered early in life to apolipoprotein E-null mice. When the micronutrient treatment was started before conception, the anti-atherosclerotic effect was stronger in the progeny. This finding correlated with decreased post-prandial triglyceridaemia and vascular inflammation, two major atherogenic factors. CONCLUSION: Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridaemia, liver steatosis, and atherosclerosis in mice, and thus our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worthy of being tested in humans.

Role of fat oxidation in the long-term stabilization of body weight in obese women.

Two studies were performed to investigate the association between body fat mass and fat oxidation. The first, a cross-sectional study of 106 obese women maintaining stable body weight, showed that these two variables were significantly correlated (r = 0.56, P less than 0.001) and the regression coefficient indicated that a 10-kg change in fat mass corresponded to a change in fat oxidation of approximately 20 g/d. The second, a prospective study, validated this estimate and quantifies the long-term adaptations in fat oxidation resulting from body fat loss. Twenty-four moderately obese women were studied under controlled dietary conditions at stable weight before and after mean weight and fat losses of 12.7 and 9.8 kg, respectively. The reduction in fat oxidation was identical to that predicted by the above regression. We conclude that changes in fat mass significantly affect fat oxidation and that this process may contribute to the long-term regulation of fat and energy balance in obese individuals.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Body composition by X-ray absorptiometry and bioelectrical impedance in chronic respiratory insufficiency patients.

Nutrition assessment is important during chronic respiratory insufficiency to evaluate the level of malnutrition or obesity and should include body composition measurements. The appreciation of fat-free and fat reserves in patients with chronic respiratory insufficiency can aid in designing an adapted nutritional support, e.g., nutritional support in malnutrition and food restriction in obesity. The purpose of the present study was to cross-validate fat-free and fat mass obtained by various bioelectric impedance (BIA) formulas with the fat-free and fat mass measured by dual-energy X-ray absorptiometry (DXA) and determine the formulas that are best suited to predict the fat-free and fat mass for a group of patients with severe chronic respiratory insufficiency. Seventy-five patients (15 women and 60 men) with chronic obstructive and restrictive respiratory insufficiency aged 45-86 y were included in this study. Body composition was calculated according to 13 different BIA formulas for women and 12 for men and compared with DXA. Because of the variability, calculated as 2 standard deviations, of +/- 5.0 kg fat-free mass for women and +/- 6.4 kg for men for the best predictive formula, the use of the various existing BIA formulas was considered not clinically relevant. Therefore disease-specific formulas for patients with chronic respiratory insufficiency should be developed to improve the prediction of fat-free and fat mass by BIA in these patients.

Whole body protein synthesis and energy expenditure in very low birth weight infants.

The aim of the present work was to study whole body protein synthesis and breakdown, as well as energy metabolism, in very low birth weight premature infants (less than 1500 g) during their rapid growth phase. Ten very low birth weight infants were studied during their first and second months of life. They received a mean energy intake of 114 kcal/kg X day and 3 g protein/kg X day as breast milk or milk formula. The average weight gain was 15 g/kg X day. The apparent energy digestibility was 88%, i.e. 99 kcal/kg X day. Their resting postprandial energy expenditure was 58 kcal/kg X day, indicating that 41 kcal/kg X day was retained. The apparent protein digestibility was 89%, i.e. 2.65 g/kg X day. Their rate of protein oxidation was 0.88 g/kg X day so that protein retention was 1.76 g/kg X day. There was a linear relationship between N retention and N intake (r = 0.78, p less than 0.001). The slope of the regression line indicates a net efficiency of N utilization of 67%. Estimates of body composition from the energy balance, coupled with N balance method, showed that 25% of the gain was fat and 75% was lean tissue. Whole body protein synthesis and breakdown were determined using repeated oral administration of 15N glycine for 60-72 h, and 15N enrichment in urinary urea was measured. Protein synthesis averaged 11.2 g/kg X day and protein breakdown 9.4 g/kg X day. Muscular protein breakdown, as estimated by 3-methylhistidine excretion, contributed to 12% of the total protein breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Body image perception and weight-related behaviour among adolescents of the Seychelles

Background: We examined one's own body image perception and its association with reported weight-related behavior among adolescents of a rapidly developing country in the African region. Methods: We conducted a school-based survey of 1432 students aged 11-17 years in the Seychelles. Weight and height were measured, and thinness, normal weight and overweight were assessed along standard criteria. A self-administered and anonymous questionnaire was administered. Perception of body image was assessed using both a closed-ended question (CEQ) and the Stunkard's pictorial silhouettes (SPS). Finally, a question assessed voluntary attempts to change weight. Results: Overall, 14.1% of the students were thin, 63.9% were normal-weight, and 22.0% were overweight or obese. There was fair agreement between actual weight status and self-perceived body image based on either CEQ or SPS. However, a substantial proportion of the overweight students did not consider themselves as overweight (SPS: 24%, CEQ: 34%) and, inversely, a substantial proportion of the normal-weight students considered themselves as too thin (SPS: 29%, CEQ: 15%). Among the overweight students, an adequate attempt to lose weight was reported more often by boys and girls who perceived themselves as overweight vs. not overweight (72-88% vs. 40-71%, p <0.05 for most comparisons). Among the normal-weight students, an inadequate attempt to gain weight was reported more often by boys and girls who perceived themselves as thin vs. not thin (27-68% vs. 11-19%, p <0.05). Girls had leaner own body ideals than boys. Conclusions: We found that substantial proportions of overweight students did not perceive themselves as overweight and/or did not want to lose weight and, inversely, that many normalweight students perceived themselves as too thin and/or wanted to gain weight: this points to forces that can drive the upwards overweight trends. Appropriate perception of one's weight was associated with adequate weight-control behavior, although not strongly, emphasizing that appropriate weight perception is only one of several factors driving adequate weight-related behavior. These findings emphasize the need to address appropriate perception of one's own weight and adequate weight-related behavior in adolescents for both individual and community weight-related interventions.

Metabolism of oral glucose in children born small for gestational age : evidence for an impaired whole body glucose oxidation

Résumé Les études épidémiologiques indiquent que la restriction intra-utérine confère un risque accru de développement de diabète de type 2 au cours de la vie. Certaines études ont documenté la présence d'une résistance à l'insuline chez les jeunes adultes ou les adolescents nés petits pour l'âge gestationnel. Comme la plupart des études ont impliqués des individus post-pubères et comme la puberté influence de manière marquée le métabolisme énergétique, nous avons évalué le devenir du glucose administré oralement dans un groupe incluant essentiellement des enfants pré-pubères ou en début de puberté avec restriction intra-utérine, et chez des enfants matchés pour l'âge et pour le poids. Tous les enfants ont eu une évaluation de leur composition corporelle par mesure des plis cutanés. Ils ont ensuite été étudiés dans des conditions standardisées et ont reçu 4 charges consécutives orales de glucose à raison de 180 mg/kg de poids corporel jusqu'à atteindre un état d'équilibre relatif. La dépense énergétique et l'oxydation des substrats ont été évaluées durant la quatrième heure par calorimétrie indirecte. Comparativement avec les enfants matchés pour l'âge et le poids, les enfants nés petits pour l'âge gestationnel avaient une plus petite stature. Leur dépense énergétique n'était pas significativement abaissée, mais leur oxydation du glucose était plus basse. Ces résultats indiquent que des altérations métaboliques sont présentes précocement chez les enfants nés petits pour l'âge gestationnel, et qu'elles sont possiblement reliées à des altérations de la composition corporelle. Abstract: Epidemiological studies indicate that intrauterine growth restriction confers an increased risk of developing type 2 diabetes mellitus in subsequent life. Several studies have further documented the presence of insulin resistance in young adults or adolescent children born small for gestational age. Since most studies addressed postpubertal individuals, and since puberty markedly affects energy metabolism, we evaluated the disposal of oral glucose in a group including mainly prepubertal and early pubertal children with intrauterine growth restriction and in healthy age- and weight-matched control children. All children had an evaluation of their body composition by skinfold thickness measurements. They were then studied in standardized conditions and received 4 consecutive hourly loads of 180 mg glucose/kg body weight to reach a near steady state. Energy expenditure and substrate oxidation were evaluated during the fourth hour by indirect calorimetry. Compared to both age- and weight-matched children, children born small for gestational age had lower stature. Their energy expenditure was not significantly decreased, but they had lower glucose oxidation rates. These results indicate that metabolic alterations are present early in children born small for gestational age, and are possibly related to alterations of body composition.

Répercussions de l'agression sur le métabolisme et la composition corporelle chez l'individu obèse : Nutrition de l'obèse agressé. [Repercussions of injury on metabolic and body composition factors in obese individuals : Nutrition and obese critical patients]

La réponse métabolique de l'obèse apparemment « sainen situation d'agression aiguë (polytraumatisés, traumatisés crâniens, patients chirurgicaux, grands brûlés, opérations électives) ne se distingue pas ou peu de celle de l'individu non-obèse. Cependant, les complications médicales liées à l'agression (insuffisances respiratoire et cardiaque, bronchopneumonie, infections de plaies, thrombophlébites et embolies) demeurent plus importantes chez l'obèse morbide que chez l'individu de poids normal. Grâce à l'inflation de ses réserves énergétiques, l'obèse apparemment sain est avantagé, par rapport au sujet mince, au cours d'une agression nutritionnelle chronique telle que le jeûne prolongé. Le facteur fonctionnel limitant la survie dépend avant tout de la composition corporelle initiale et du degré d'adaptation métabolique (et comportementale) en particulier du degré de conservation de la masse maigre par rapport à la masse grasse. La mobilisation accrue de la masse grasse associée à la perte de poids chez l'obèse (par rapport à son homologue non-obèse) est favorable à une prolongation de la vie, car, en brûlant davantage de graisse corporelle, la part des protéines corporelles endogènes utilisée à des fins énergétiques est plus faible. Il s'ensuit chez l'obèse qu'un niveau de masse maigre critique pour la survie n'est atteint qu'après une réduction très marquée de ses réserves énergétiques. En revanche, le sujet mince perd davantage de masse maigre lors de l'amaigrissement et, par conséquent, son métabolisme de repos diminuera plus rapidement que celui du sujet obèse. Cela peut constituer un avantage énergétique évident en termes d'économie d'énergie consécutive à l'adaptation métabolique, mais un inconvénient majeur quant à la durée de la survie. The metabolic response of « apparently healthyobese individuals following acute injury (multiple trauma, head injury and surgical patients, extended burns, elective surgery) is not dramatically different from that of a non-obese individuals. However, the medical complications following the injury (respiratory and cardiac insufficiency, broncho-pneumonia, infections of wounds, trombophlebitis and embolism) are more prevalent in morbid obese patients than in individuals of normal body weight. Because of a large increase in their individuals energy store, "apparently healthy" obese individuals have an advantage over very lean subjects when exposed to a chronic nutritional aggression such as total fasting. The functional limiting factor for survival depends primarily on initial body composition and the magnitude of metabolic adaptation (including behavioral adaptation). The key factor is the extent to which the fat-free mass is maintained (versus to the fat mass) during weight loss. The increased proportion of body fat mobilized during weight loss in obese patients, compared with their non-obese counterparts, favors prolonged survival, because more adipose tissue is burned off, the fraction of body protein endogenously utilized for energy purpose individuals, is smaller. This implies that obese individuals do not reach a fat-free mass "critical" for their survival until their energy stores reach very low values. In contrast, lean subject tend to lose more fat-free mass during weight loss than obese subjects and, as a result, their energy expenditure drops more rapidly. This may offer a potential advantage in terms of energy economy (more energy saving) but a major disadvantage in terms of duration of survival.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.