Low resilience in severe obesity: marker of adverse childhood experiences and current psychological disorders.

PURPOSE: Psychological disorders, early-age psychological traumas and eating disorders may contribute to the development of severe obesity in vulnerable individuals. Resilience may serve a protective role against binge eating disorder or depression. The current study aimed to investigate the relationship between adverse childhood experiences (ACE), resilience, and current psychological disorders. It also examined whether resilience plays a protective role in this pathway in a cohort of patients seeking bariatric surgery. METHODS: Two hundred patients (153 women, 47 men) with severe obesity scheduled for bariatric surgery at the CHRU Nancy were included between September 2016 and April 2017. Participants completed the Resilience Scale for Adults (RSA) questionnaire and underwent a structured interview on ACE and current psychological disorders. RESULTS: Mean total RSA score was 5.16 ± 0.87. The most frequent ACE were emotional neglect (90.5%) and emotional abuse (61%); 96% reported at least one ACE; 67% presented at least one current psychological disorder, the most frequent being anxiety (36%) and BED (35%). The number of psychological disorders, cumulative ACE and age explained 19.5% of the variance in total RSA score (p < 0.0001; adjusted R2 = 0.19). The association of cumulative ACE and number of psychological disorders was mediated by resilience. CONCLUSION: Our findings suggest that resilience is a relevant component of the psychosocial phenotype of severe obesity in bariatric surgery candidates. Resilience seems to play a partly mediation role in the relationship between ACE and psychological disorders. Low resilience becomes a marker that underscores the necessity to examine in greater depth ACE and psychological disorders. LEVEL OF EVIDENCE: Level III, cohort analytic study.

Five-Year Changes in Weight and Diabetes Status After Bariatric Surgery for Craniopharyngioma-Related Hypothalamic Obesity: a Case-Control Study.

PURPOSE: Craniopharyngiomas are tumors located in the hypothalamic region which leads to obesity in about 50% of cases. Long-term efficacy and safety of bariatric surgery are lacking in this peculiar population. The aim of this study is to determine the 5-year weight loss and resolution of type 2 diabetes (T2D) after bariatric surgery in patients operated on craniopharyngioma who had developed hypothalamic obesity. MATERIALS AND METHODS: This is a multicenter french retrospective case-control study. Subjects with craniopharyngioma (n = 23) who underwent sleeve gastrectomy (SG) (n = 9) or Roux-en-Y gastric bypass (RYGB) (n = 14) (median age 35 years [25;43] and BMI 44.2 kg/m2 [40.7; 51.0]; 8/23 with T2D) were individually matched to 2 subjects with common obesity for age, gender, preoperative body mass index, T2D, and type of surgery. RESULTS: TWL% after 1 and 5 years was lower in the craniopharyngioma group than in the control group: 23.1 [15.4; 31.1] (23/23) vs 31.4 [23.9; 35.3] at 1 year (p = 0.008) (46/46) and 17.8 [7.1; 21.9] (23/23) vs 26.2 [18.9; 33.9] at 5 years (p = 0.003) (46/46). After RYGB, TWL% was lower in the craniopharyngioma group compared to the control group (p < 0.001) and comparable after SG both at 1 and 5 years. No difference between the two groups was observed in T2D remission rate and in early and late adverse events. No hormonal deficiency-related acute disease was reported. CONCLUSIONS: Bariatric surgery induced a significant weight loss in the craniopharyngioma group at 1 and 5 years, but less than in common obesity. SG may be more effective than RYGB but this remains to be demonstrated in a larger cohort.

Insulin resistance is more severe in patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is associated with an increased cardiovascular mortality, and its underlying mechanisms remain unclear. Insulin resistance has been suggested with low level of evidence. The goal of this study was to evaluate glucose metabolism and insulin resistance in primary hyperparathyroidism patients, to compare with control subjects, and to identify risk factors for insulin resistance in patients with primary hyperparathyroidism. METHODS: Cross-sectional study of consecutive primary hyperparathyroidism patients without history of diabetes or severe chronic kidney disease (glomerular filtration rate ≤30 mL/min/1.73 m2). Fasting glucose and insulin were evaluated before parathyroidectomy. Glucose metabolism was compared with population-based control subjects (n = 171). RESULTS: One hundred and seventy-four patients with primary hyperparathyroidism (140 females) were included. Mean fasting glucose was 0.983 ± 0.129 g/L, and 63 patients (36%) had prediabetes (>1.0 g/L). Mean Homeostatic model assessment of insulin resistance (HOMA-IR) was 3.386 ± 3.111 mUI/L, and 78 patients (45%) had insulin resistance (HOMA-IR >2.6). Blood calcium levels (0.171; P = .023) and body mass index (0.450; P < .001) were correlated positively with HOMA-IR. Insulin secretion (HOMA-B%) was correlated positively with preoperative systolic blood pressure in mm Hg (0.187; P = .013). In multivariate analysis, classic hypercalcemic primary hyperparathyroidism (18.47, 6.84-49.87; <.001), mild hypercalcemic primary hyperparathyroidism (5.35, 2.40-11.95; <.001), and body mass index (1.27, 1.17-1.38; <.001) remained independent predictors for insulin resistance (HOMA-IR >2.6). When compared with control subjects, mean HOMA-IR was significantly higher in primary hyperparathyroidism patients (3.386 ± 3.111 vs 1.919 ± 1.158; P < .001). CONCLUSION: Insulin resistance was significantly higher in primary hyperparathyroidism patients than in control subjects. The impact of parathyroidectomy on insulin resistance should be evaluated in patients with higher calcium levels.

Low-frequency Coding Variants Associated With Body Mass Index Affect the Success of Bariatric Surgery.

CONTEXT: A recent study identified 14 low-frequency coding variants associated with body mass index (BMI) in 718 734 individuals predominantly of European ancestry. OBJECTIVE: We investigated the association of 2 genetic scores (GS) with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. METHODS: The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective GS based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. RESULTS: While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they affect BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. CONCLUSION: Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also affect the outcomes of bariatric surgery in patients with severe/morbid obesity.

Impact of severe SARS-CoV-2 infection on nutritional status and subjective functional loss in a prospective cohort of COVID-19 survivors.

The nutritional sequelae of COVID-19 have not been explored in a large cohort study. OBJECTIVES: To identify factors associated with the change in nutritional status between discharge and 30 days post-discharge (D30). Secondary objectives were to determine the prevalence of subjective functional loss and severe disability at D30 and their associated factors. METHODS: Collected data included symptoms, nutritional status, self-evaluation of food intake, Performance Status (PS) Scale, Asthenia Scale, self-evaluation of strength (SES) for arms and legs at discharge and at D30. An SES <7 was used to determine subjective functional loss. A composite criteria for severe disability was elaborated combining malnutrition, subjective functional loss and PS >2. Patients were classified into three groups according to change in nutritional status between discharge and D30 (persistent malnutrition, correction of malnutrition and the absence of malnutrition). RESULTS: Of 549 consecutive patients hospitalised for COVID-19 between 1 March and 29 April 2020, 130 died including 17 after discharge (23.7%). At D30, 312 patients were at home, 288 (92.3%) of whom were interviewed. Of the latter, 33.3% were malnourished at discharge and still malnourished at D30, while 23.2% were malnourished at discharge but no longer malnourished at D30. The highest predictive factors of persistent malnutrition were intensive care unit (ICU) stay (OR=3.42, 95% CI: 2.04 to 5.75), subjective functional loss at discharge (OR=3.26, 95% CI: 1.75 to 6.08) and male sex (OR=2.39, 95% CI: 1.44 to 3.97). Subjective functional loss at discharge (76.8%) was the main predictive factor of subjective functional loss at D30 (26.3%) (OR=32.6, 95% CI: 4.36 to 244.0). Lastly, 8.3% had a severe disability, with a higher risk in patients requiring an ICU stay (OR=3.39, 95% CI: 1.43 to 8.06). CONCLUSION: Patients who survived a severe form of COVID-19 had a high risk of persistent malnutrition, functional loss and severe disability at D30. We believe that nutritional support and rehabilitation should be strengthened, particularly for male patients who were admitted in ICU and had subjective functional loss at discharge. TRIAL REGISTRATION NUMBER: NCT04451694.

Obesity and mortality in critically ill COVID-19 patients with respiratory failure.

BACKGROUND: Patients with obesity are at increased risk of severe COVID-19, requiring mechanical ventilation due to acute respiratory failure. However, conflicting data are obtained for intensive care unit (ICU) mortality. OBJECTIVE: To analyze the relationship between obesity and in-hospital mortality of ICU patients with COVID-19. SUBJECTS/METHODS: Patients admitted to the ICU for COVID-19 acute respiratory distress syndrome (ARDS) were included retrospectively. The following data were collected: comorbidities, body mass index (BMI), the severity of ARDS assessed with PaO2/FiO2 (P/F) ratios, disease severity measured by the Simplified Acute Physiology Score II (SAPS II), management and outcomes. RESULTS: For a total of 222 patients, there were 34 patients (15.3%) with normal BMI, 92 patients (41.4%) who were overweight, 80 patients (36%) with moderate obesity (BMI:30-39.9 kg/m2), and 16 patients (7.2%) with severe obesity (BMI ≥ 40 kg/m2). Overall in-hospital mortality was 20.3%. Patients with moderate obesity had a lower mortality rate (13.8%) than patients with normal weight, overweight or severe obesity (17.6%, 21.7%, and 50%, respectively; P = 0.011. Logistic regression showed that patients with a BMI ≤ 29 kg/m2 (odds ratio [OR] 3.64, 95% CI 1.38-9.60) and those with a BMI > 39 kg/m2 (OR 10.04, 95% CI 2.45-41.09) had a higher risk of mortality than those with a BMI from 29 to 39 kg/m2. The number of comorbidities (≥2), SAPS II score, and P/F < 100 mmHg were also independent predictors for in-hospital mortality. CONCLUSIONS: COVID-19 patients admitted to the ICU with moderate obesity had a lower risk of death than the other patients, suggesting a possible obesity paradox.

OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions.

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.

Evolution and Predictive Factors of Improvement of Obstructive Sleep Apnea in an Obese Population After Bariatric Surgery.

STUDY OBJECTIVES: Our objectives were to determine in an obese population (body mass index > 35 kg/m²) the number of patients, after gastric bypass (GBP), who no longer met French Ministry of Health criteria for utilizing positive airway pressure (PAP), and the predictive factors of obstructive sleep apnea (OSA) improvement. METHODS: Between June 2012 and August 2014 we diagnosed OSA in 129 incident patients requiring PAP therapy before GBP. A postoperative sleep recording was undertaken for 44 of these patients after a weight loss of at least 10%. RESULTS: Most of the patients showed severe OSA with a mean [standard deviation] apnea-hypopnea index (AHI) of 52.8 [23.8] events/h. The body mass index was 46.1 [5.1] kg/m². All the patients were treated via PAP and most of them via auto-titrating PAP with a range of 4-16 cmH2O. Following the GBP, in 31 patients (70.5%) OSA was improved, allowing PAP to be stopped (AHI < 15 events/h). The Epworth Sleepiness Scale score, the modified Medical Research Council dyspnea scale, the loudness of snoring, and sleep structure were improved. AHI was decreased by a mean of 40.9 [22.4] events/h (P < .001). In a multivariate logistic regression model, age (P = .018) and sleep oxygen desaturation index (P = .049) appeared to predict improvement of OSA. CONCLUSIONS: After GBP, 70.5% of the patients no longer met French Ministry of Health criteria for utilizing PAP, allowing discontinuation of this treatment. At diagnosis, a younger age and a less severe sleep oxygen desaturation were predictive factors of this improvement.

Links between traumatic experiences in childhood or early adulthood and lifetime binge eating disorder.

OBJECTIVES: To evaluate the association between childhood or early adulthood traumatic experiences and adulthood binge eating disorder (BED) in 326 male and 1158 female patients. A structured clinical interview for the DSM-IV (SCID-I/P)-adapted to lifetime exploration for the diagnosis of BED and for DSM-IV Childhood Disorders was conducted by the psychiatrist. RESULTS: Emotional neglect was the most frequent event experienced (77.8% of females vs. 63.5% of males, p < 0.0001), ahead of physical abuse (23.3%), witnessed domestic violence (17.7%) and sexual abuse (11.8% of females vs. 2.8% of males (p < 0.0001)). The prevalence rate for BED in the whole population was 34.9%. The independent predictors for BED were emotional neglect in male obese patients (OR = 3.49; IC95% (1.94-6.29); p < 0.0001) and physical abuse (OR = 1.56; IC95% (1.14-2.12); p = 0.0047), emotional neglect (OR = 1.83; IC95% (1.37-2.44); p < 0.0001), and sexual abuse (OR = 1.80; IC95% (1.22-2.65); p = 0.0029) in female patients. With a cut-off value of 17, the sensitivity of the Binge Eating Scale for BED during lifetime was 50.8% with 74.7% specificity. CONCLUSIONS: This study shows that early psychological events are independent predictors of BED in obese female and male adults. The BES questionnaire is a poor predictor of BED during lifetime and a structured clinical interview should be recommended.

Weight loss expectations and determinants in a large community-based sample.

While weight-loss expectations have primarily been studied in people enrolled in weight-loss programs, the present study explores patient expectations about weight-loss and identifies related determinants in a large, non-clinical population. 3916 volunteers (age > 18 years) participated in 2012 in a community-based survey in the French-speaking region of Belgium. Participants were asked to define "dream", "goal", "happy", "acceptable", and "disappointed" weights. Other self-reported measures were used to determine each participant's body mass index (BMI), body image discrepancy (BID), subjective norm (SN), weight loss activity, weight history, quality of life (QoL), and demographic and socioeconomic characteristics. The study focused on the determinants of unrealistic weight-loss "goal" (≥10% of initial weight). Results showed median weight loss targets ranged from 5 kg ("disappointed" weight loss) to 21 kg ("dreamed" weight loss). Respondents considered the recommended weight-loss target (5-10%) disappointing. Severe and morbid obesity categories are at high risk of unrealistic weight loss goal. Unrealistic weight-loss goals was associated with female gender, weight loss activity, overweight history and lower QoL in overweight and moderate obesity respondents. These findings confirm the urgent need to help patients accept more modest weight loss outcomes and the need for personalized care that considers the patient's specific profile and both weight loss expectations and determinants.

From therapeutic patient education principles to educative attitude: the perceptions of health care professionals - a pragmatic approach for defining competencies and resources.

Educative attitude is an essential, if implicit, aspect of training to acquire competency in therapeutic patient education (TPE). With multiple (or nonexistent) definitions in the literature, however, the concept needs clarification. The primary aim of this study was to analyze the representations and transformations experienced by health care professionals in the course of TPE training in order to characterize educative attitude. We conducted an exploratory qualitative study using several narrative research-based tools with participants of two TPE continuing education courses. We then performed an inductive thematic analysis. Thirty-three people participated in the study; the majority were women (n=29), nurses (n=17) working in a hospital setting (n=28). Seven categories of statements were identified: time-related ("the right moment, how much time it takes"), the benefits of TPE (to health care professionals' personal well-being), emotions and feelings (quality of exchanges, sharing), the professional nature of TPE (educational competencies required), the holistic, interdisciplinary approach (complexity of the person and value of teamwork), the educational nature of the care relationship (education an integral part of care) and the ethical dimension (introspection essential). The first three components appear fairly innovative, at least in formulation. The study's originality rests primarily in its choice of participants - highly motivated novices who expressed themselves in a completely nontheoretical way. Health models see attitude as critical for adopting a behavior. Best TPE practices should encourage personal work on this, opening professionals to the social, experiential and emotional aspects of managing chronic illness.

Perioperative thromboprophylaxis in severely obese patients undergoing bariatric surgery: insights from a French national survey.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in obese patients undergoing bariatric surgery (BS), but there is neither consensus nor high-level guidelines yet on VTE prophylaxis in this specific population. OBJECTIVE: We aimed to evaluate patterns of BS perioperative thromboprophylaxis practices. SETTING: French obesity specialized care centers (CSO), which are tertiary care referral hospitals for the most severe cases of obesity METHODS: A detailed questionnaire survey (11 opened, 15 closed questions) investigating their prophylactic schemes of anticoagulation (molecule, dose, weight-adjustment, duration, associated measures, follow-up) was sent to the 37 CSO. RESULTS: Completion rate was 92%. Over 90% of respondents indicated using low molecular weight heparin. Enoxaparin was the most commonly used molecule (89%), twice daily (71%), started mostly 6 hours after BS (74%), whereas fondaparinux (9%), dalteparin (6%), and tinzaparin (6%) were less often prescribed. Dosing varied significantly according to centers from 4000 to 12,000 IU/d, with the most commonly used dose being 8000 IU once daily, 83%, as well as treatment duration (1 week, 9%; 3 weeks, 47%). Half CSO adjusted low molecular weight heparin dose to weight. Biological monitoring was performed in 88%. Only 1 center followed systematically anti-Xa activity. Associated measures such as elastic stoking or intermittent pneumatic compression were used in 32% and 26%, respectively, and both were used in 39%. CONCLUSION: This study finds significant discrepancies in thromboprophylaxis practices in obese patients undergoing BS, particularly with respect to treatment duration and dose adjustment, highlighting the urgent need for improved implementation of existing clinical practice guidelines in this VTE high-risk population.

Body image discrepancy and subjective norm as mediators and moderators of the relationship between body mass index and quality of life.

BACKGROUND AND OBJECTIVE: Despite the strength and consistency of the relationship between body mass index (BMI) and quality of life (QoL), a reduction in BMI does not necessarily lead to an improvement in QoL. Between-subject variability indicates the presence of mediators and moderators in the BMI-QoL association. This study aimed to examine the roles of body image discrepancy (BID) and subjective norm (SN) as potential mediators and moderators. SUBJECTS AND METHODS: In 2012, 3,016 volunteers (aged ≥18 years) participated in a community-based survey conducted in the French-speaking region of Belgium. Participation was enhanced using a large multimedia campaign (which was supported by a large network of recruiters) that employed the nonstigmatizing slogan, "Whatever your weight, your opinion will count". Participants were invited to complete a web-based questionnaire on their weight-related experiences. Self-reported measures were used to calculate each participant's BMI, BID, SN, and QoL (a French obesity-specific QoL questionnaire was used to calculate the participants' physical dimension of QoL scores [PHY-QoL], psychosocial dimension of QoL scores [PSY/SOC-QoL], and their total scores). The covariates included gender, age, subjective economic status, level of education, household size, and perceived health. The mediation/moderation tests were based on Hayes' method. RESULTS: Tests showed that the relationships between BMI and PHY-QoL, PSY/SOC-QoL, and TOT-QoL were partially mediated by BID in both males and females and by SN in females. Moreover, BID was a moderator of the relationship between BMI and PSY/SOC-QoL in males and females. SN was a moderator of the relationship between BMI and PSY/SOC-QoL in males and between BMI and total scores in males (when used without BID in the models). CONCLUSION: BID and SN should be considered as important factors in obesity management strategies. The study shows that targeting BMI only is not sufficient to improve the QoL of overweight and obese subjects, and that other variables, including perceptual factors, should be considered.

[Cross-border evaluation of needs for training in therapeutic education of the patient for the management in type 2 diabetes and obesity: Survey by method of nominal group with healthcare professionals]. / Étude transfrontalière des besoins de formation en éducation thérapeutique du patient pour la prise en charge du diabète de type 2 et de l'obésité : enquête par groupes nominaux auprès des professionnels de santé.

INTRODUCTION: The design of continuous training programs in therapeutic patient education (ETP) should be inspired by needs shown by the professionals concerned in terms of mobilization or acquisition of skills in this domain. The objective of this study is to analyze needs expressed by healthcare professionals (HP) involved in patients' management presenting a type 2 diabetes (T2D) and/or obesity and to compare them with the existing recommendations. METHODS: One hundred and five PS (general practitioners, dietitians and nurses) of 3 frontier regions of French-speaking European countries (France, Belgium and Grand duchy of Luxembourg) were questioned in 12 monodisciplinary groups according to the technique of the nominal group. Needs expressed by the participants were classified in the categories of the reference table of skills to dispense TPE (National Institute for Health Prevention and Education [INPES], 2013). RESULTS/DISCUSSION: Among needs expressed by HP, 52 % of the votes targeted relational skills, 10 % of the skills relative to the biomedical techniques, 20 % of the skills relative to the educational techniques and 11 %, those of organization and the coordination. Seven percent of the proposals were out of the categories of the INPES. Results do not allow to establish profiles of skills according to the studied region or profession. The recognition of the TPE by the French legislation does not seem to influence in a major way the data. CONCLUSION: The needs expressed by PS in the context of this study are focused on the relation HP/patient that is the heart of the TPE. It would however be necessary to raise awareness among HP in the acquisition of the other skills which concern in particular the animation of group, the interprofessional coordination, the consideration of the environment or more generally the procedures.

Regulation of SREBPs by Sphingomyelin in Adipocytes via a Caveolin and Ras-ERK-MAPK-CREB Signaling Pathway.

Sterol response element binding protein (SREBP) is a key transcription factor in insulin and glucose metabolism. We previously demonstrated that elevated levels of membrane sphingomyelin (SM) were related to peroxisome proliferator-activated receptor-γ (PPARγ), which is a known target gene of SREBP-1 in adipocytes. However, the role of SM in SREBP expression in adipocytes remains unknown. In human abdominal adipose tissue from obese women with various concentrations of fasting plasma insulin, SREBP-1 proteins decreased in parallel with increases in membrane SM levels. An inverse correlation was found between the membrane SM content and the levels of SREBP-1c/ERK/Ras/PPARγ/CREB proteins. For the first time, we demonstrate the effects of SM and its signaling pathway in 3T3-F442A adipocytes. These cells were enriched or unenriched with SM in a range of concentrations similar to those observed in obese subjects by adding exogenous natural SMs (having different acyl chain lengths) or by inhibiting neutral sphingomyelinase. SM accumulated in caveolae of the plasma membrane within 24 h and then in the intracellular space. SM enrichment decreased SREBP-1 through the inhibition of extracellular signal-regulated protein kinase (ERK) but not JNK or p38 mitogen-activated protein kinase (MAPK). Ras/Raf-1/MEK1/2 and KSR proteins, which are upstream mediators of ERK, were down-regulated, whereas SREBP-2/caveolin and cholesterol were up-regulated. In SM-unmodulated adipocytes treated with DL-1-Phenyl-2-Palmitoylamino-3-morpholino-1-propanol (PPMP), where the ceramide level increased, the expression levels of SREBPs and ERK were modulated in an opposite direction relative to the SM-enriched cells. SM inhibited the insulin-induced expression of SREBP-1. Rosiglitazone, which is an anti-diabetic agent and potent activator of PPARγ, reversed the effects of SM on SREBP-1, PPARγ and CREB. Taken together, these findings provide novel insights indicating that excess membrane SM might be critical for regulating SREBPs in adipocytes via a MAPK-dependent pathway.

Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart.

Barker's concept of 'foetal programming' proposes that intrauterine growth restriction (IUGR) predicts complex metabolic diseases through relationships that may be further modified by the postnatal environment. Dietary restriction and deficit in methyl donors, folate, vitamin B12, and choline are used as experimental conditions of foetal programming as they lead to IUGR and decreased birth weight. Overfeeding and deficit in methyl donors increase central fat mass and lead to a dramatic increase of plasma free fatty acids (FFA) in offspring. Conversely, supplementing the mothers under protein restriction with folic acid reverses metabolic and epigenomic phenotypes of offspring. High-fat diet or methyl donor deficiency (MDD) during pregnancy and lactation produce liver steatosis and myocardium hypertrophy that result from increased import of FFA and impaired fatty acid ß-oxidation, respectively. The underlying molecular mechanisms show dysregulations related with similar decreased expression and activity of sirtuin 1 (SIRT1) and hyperacetylation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). High-fat diet and overfeeding impair AMPK-dependent phosphorylation of PGC-1α, while MDD decreases PGC-1α methylation through decreased expression of PRMT1 and cellular level of S-adenosyl methionine. The visceral manifestations of metabolic syndrome are under the influence of endoplasmic reticulum (ER) stress in overnourished animal models. These mechanisms should also deserve attention in the foetal programming effects of MDD since vitamin B12 influences ER stress through impaired SIRT1 deacetylation of HSF1. Taken together, similarities and synergies of high-fat diet and MDD suggest, therefore, considering their consecutive or contemporary influence in the mechanisms of complex metabolic diseases.