Eating-related environmental factors in underweight eating disorders and obesity: are there common vulnerabilities during childhood and early adolescence?

OBJECTIVE: This study aimed to examine whether there is an association between individual, social and family influences and dysfunctional eating patterns early in life and the likelihood of developing a subsequent underweight eating disorder (ED) or obesity. METHOD: The total sample comprised 152 individuals (underweight ED, n = 45; obese patients, n = 65; healthy controls; n = 42) from Barcelona, Spain. The Cross-Cultural Questionnaire (CCQ) was used to assess early eating influences as well as individual and family eating patterns and attitudes towards food. RESULTS: Even though a few shared eating influences emerged for both groups, unique factors were also observed. Whereas relationship with friends, teasing about eating habits by family members and the mass media were of specific relevance to the underweight ED group, the patient's own physical appearance, body dissatisfaction, teasing about eating habits by friends, teasing about body shape by family members and dysfunctional eating patterns were unique to obesity. CONCLUSIONS: Overlapping environmental risk factors provide evidence for integral prevention and intervention approaches that simultaneously tackle a range of weight-related problems. The unique factors might be important for targeting high-risk individuals.

Obstructive sleep apnoea and metabolic impairment in severe obesity.

Obstructive sleep apnoea (OSA) seems to worsen metabolism. This effect has not been evaluated in morbid obesity (MO). We hypothesised that the metabolic profile is more impaired in MO patients with OSA than in those without, and investigated whether any specific metabolic dysfunction is related to OSA in MO. A prospective multicentre cross-sectional study was conducted in consecutive subjects before bariatric surgery. OSA was defined as apnoea/hypopnoea index (AHI) ≥15 by overnight polysomnography. Anthropometrical, blood pressure (BP) and fasting blood measurements were obtained the morning after. Metabolic syndrome (MetS) was defined according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. 159 patients were studied: 72% were female and 72% had OSA. MetS prevalence was 70% in OSA versus 36% in non-OSA (p<0.001). As AHI severity increased, metabolic parameters progressively worsened, even in those without type 2 diabetes (DM2). AHI was independently associated with systolic and diastolic BP, triglycerides and the percentage of glycosylated haemoglobin (HbA1c) in the total sample, and with systolic BP, high-density lipoprotein cholesterol and HbA1c in those samples without DM2. OSA increased the adjusted odds ratio of having MetS by 2.8 (95% CI 1.3-6.2; p=0.009). In MO, OSA is associated with major metabolic impairment caused by higher BP and poorer lipid and glucose control, independent of central obesity or DM2.

Paired subcutaneous and visceral adipose tissue aquaporin-7 expression in human obesity and type 2 diabetes: differences and similarities between depots.

CONTEXT: AQP7 is considered to be the sole adipose glycerol channel, and its regulation is crucial for glycemia control. OBJECTIVES: In this work, we aimed to further characterize AQP7 in human adipose tissue in obesity and type 2 diabetes (T2D): 1) to assess AQP7 expression levels in paired abdominal adipose tissue depots (sc and visceral); 2) to relate it with gene expression of genes involved in lipid metabolism; and 3) to confirm that AQP7 is mainly expressed in the adipocytes. DESIGN: We conducted a transversal study of gene expression in paired samples of sc adipose tissue (SAT) and visceral adipose tissue (VAT). PATIENTS: Caucasian lean and obese subjects (n = 62, matched for age and gender) and T2D subjects (n = 11, matched for age, gender, and BMI with their control group) participated in the study. MAIN OUTCOME MEASURE: We measured AQP7 expression levels in paired SAT and VAT. RESULTS: We have proved the presence of AQP7 mRNA and protein in the adipocyte rather than the stromovascular fraction of adipose tissue (P = 0.001) and in mature adipocytes when differentiated in vitro. Increased AQP7 mRNA expression levels in VAT from T2D obese subjects (P < 0.05) were found. AQP7 transcript levels ratio of SAT vs. VAT changed with the presence of obesity and T2D. Interestingly, there were positive associations between AQP7 and both lipogenic and lipolytic genes in a similar manner in both adipose depots. CONCLUSIONS: Taken together, these data suggest a subtle regulation between adipose depots of the sole adipose aquaporin, AQP7, which is unbalanced in obesity and T2D.

Plasma chitotriosidase activity in multiple sclerosis.

A recent study has shown that chitotriosidase (Chit) may play a role in the pathogenesis of multiple sclerosis (MS). Plasma Chit activity was investigated in 219 untreated MS patients and 160 healthy controls (HC) by means of a fluorometric enzyme activity assay. Chit activity was also measured in a subgroup of 46 patients following treatment with interferon-beta (IFNbeta). Overall, plasma Chit activity was significantly increased in MS patients compared with HC, but no differences were observed between relapsing and progressive clinical forms. In addition, Chit activity was similar between patients during relapse and patients during clinical remission. Treatment with IFNbeta was associated with a significant increase in Chit activity compared with untreated patients in both responders and non-responders to treatment. Although these findings suggest a role of Chit in MS, our data do not support an association between plasma Chit activity and MS clinical course and clinical response to IFNbeta treatment.

Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro.

OBJECTIVE: To investigate fetal antigen 1 (FA1) protein within the context of human obesity and its relation with insulin sensitivity. SUBJECTS: Cross-sectional study that analyses circulating levels of FA1 in two selected human cohorts: n=127 men for the study of FA1 circulating levels in the context of obesity and insulin sensitivity (S(i)); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied. MEASUREMENTS: Anthropometrical parameters: body mass index, waist-to-hip ratio, waist circumference, fat-free mass and fat mass. Clinical parameters: lipid profile (high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides), glycemic profile (fasting glucose, insulin, S(i), HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), cytokines (sIL-6), adipokines (adiponectin) and circulating soluble fractions of tumor necrosis factor-alpha receptors 1 and 2 (sTNFR1 and sTNFR2). RESULTS: IN the obesity study, levels of FA1 in serum were found to increase with obesity. The S(i) index was negatively dependent on FA1 levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin). CONCLUSION: FA1 serum levels were increased in obese subjects and might influence S(i). The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory environment observed in obesity.

Low 25-hydroxyvitamin D concentrations in obese women: their clinical significance and relationship with anthropometric and body composition variables.

UNLABELLED: Obesity is associated with low concentrations of 25-hydroxyvitamin D [25(OH) D]. However, conflicting results have been found regarding the relationship of 25(OH) D with anthropometric and adiposity parameters. The aim of our study was to analyze the association between 25(OH) D and body fat (BF) in a homogeneous cohort of non-obese, obese, and morbidly obese Caucasian women. The study was performed in L'Hospitalet de Llobregat, a city adjacent to Barcelona with a latitude of 41 degrees, 22 minutes, and 5 seconds north. MATERIALS AND METHODS: Plasma concentrations of 25(OH) D were determined and body composition was evaluated by bioelectrical impedance in a group of 43 women with morbid obesity, 28 non-morbidly obese, and 50 non-obese women matched for age. RESULTS: Morbidly obese women showed lower 25(OH) D concentrations compared to non-morbidly and non-obese women (37.9+/-16 vs 40.2+/-13 vs 56.7+/-21 nmol/l, p=0.001). Fifty-one percent of morbidly obese women had vitamin D deficiency [25(OH) D<38 nmol/l] compared to 22% of non-obese patients, (p=0.004). In the bivariate correlation analysis 25(OH) D was inversely associated with weight (r=-0.41, p=0.001), body mass index (BMI) (r=-0.432, p=0.001), waist to hip ratio (WHR)(r=-0.40, p=0.001), BF (r=-0.53, p=0001), fat mass (r=-0.44, p=0.0001), fat-free mass (r=-0.35, p=0.001). In the multivariate general linear model analysis, 25(OH) D was associated with season of examination (p=0.001) and was negatively associated with BF (beta=-0.75, p=0.001), after adjusting for age, BMI, and WHR. CONCLUSIONS: 25(OH) D concentrations are associated with body composition variables especially by BF, independently of seasonal variability. Therefore, body adiposity should be considered when assessing vitamin D requirements in obese patients.

Effect of weight loss induced by gastric bypass on proinflammatory interleukin-18, soluble tumour necrosis factor-alpha receptors, C-reactive protein and adiponectin in morbidly obese patients.

OBJECTIVE: Interleukin-18 (IL-18) is a potent proinflammatory cytokine whose role in human obesity has recently been suggested. The aim of our study was to analyse in morbidly obese patients undergoing gastric bypass, the relationship of IL-18 with insulin resistance and with proinflammatory cytokines (tumour necrosis factor-alpha receptors, sTNFR), C-reactive protein (CRP) and with adiponectin. DESIGN: Observational and prospective study. PATIENTS: Sixty-five morbidly obese patients, aged 45 +/- 8.9 years, were studied before and 12 months after gastric bypass. MEASUREMENTS: We analysed plasma concentrations of IL-18, sTNFR, CRP and adiponectin. RESULTS: Plasma concentrations of sTNFR2, IL-18 and CRP were decreased and adiponectin significantly increased after bypass surgery. In the multiple regression analysis, preoperative values of IL-18 remained significantly associated with preoperative triglycerides (beta = 0.47, P = 0.005) and TNFR2 (beta = 0.47, P = 0.004). R(2) for the model = 0.38. Postoperative IL-18 concentrations in the multiple regression analysis were significantly associated with postoperative homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.092, P = 0.019) and triglycerides (beta = 0.40, P = 0.036). R(2) for the model = 0.46. IL-18 did not correlate with body mass index, fat mass, fat-free mass or body fat. No relationship was either found between adiponectin and IL-18, TNFR1 and -2 and CRP. CONCLUSIONS: Massive weight loss induced by gastric bypass reduces IL-18, TNFR2 and CRP. IL-18 might be a marker of the chronic inflammatory process underlying insulin resistance but its lack of association with anthropometric and body composition parameters does not support a major secretion by human adipocytes. IL-18 and sTNFR1 and -2 do not play a main role in the inhibition of the secretion of adiponectin.

Adipose tissue expression of the glycerol channel aquaporin-7 gene is altered in severe obesity but not in type 2 diabetes.

CONTEXT: Aquaporin-7 is required for efflux of glycerol from adipocytes and influences whole-body glucose homeostasis in animal studies. OBJECTIVE: Our objective was to test the hypothesis that AQP7 gene expression levels may be affected by presence of obesity and type 2 diabetes in humans. DESIGN: The obesity study cohort consisted of 12 lean, 22 nonseverely obese, and 13 severely obese subjects. The type 2 diabetes study cohort consisted of 17 lean and 39 obese type 2 diabetic patients. Circulating levels of plasma soluble proteins monocyte chemoattractant protein-1, TNF receptors 1 and 2, and IL-6 and glycerol were measured. The sc adipose tissue gene expression of AQP7, MCP-1, IL-6, TNFalpha, PPARgamma, and SREBP1c genes was measured by real-time PCR. AQP7 gene mutation analysis was performed. RESULTS: Severely obese women showed lower AQP7 expression levels compared with lean and nonseverely obese (P < 0.001). Moreover, circulating glycerol concentration was lower in severely obese subjects, but no correlation with AQP7 adipose tissue expression was observed. AQP7 expression was negatively related with proinflammatory genes (for monocyte chemoattractant protein-1, r = -0.203 and P = 0.044; for TNFalpha, r = -0.209 and P = 0.036). Concerning adipogenic factors, AQP7 expression levels were found to be positively determined by PPARgamma mRNA expression levels (r = 0.265; P = 0.012). AQP7 expression did not show differences regarding the presence of type 2 diabetes. CONCLUSION: Expression of AQP7 is down-regulated in women with severe obesity. The expression of this glycerol channel is not affected by type 2 diabetes.

IL-18: relationship with anthropometry, body composition parameters, leptin and arterial hypertension.

OBJECTIVE: Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine with potential atherogenic properties whose role in human obesity has been recently suggested. The aim of our study was to analyze the physiologic distribution of IL-18 among sexes and all decades of the adult life in a healthy population randomly selected and to study its relationship with anthropometric, body composition measurements and leptin concentrations. We also studied the relationship of IL-18 with smoking and arterial hypertension, known risk factors implicated in atherogenesis. MATERIALS AND METHODS: One hundred and thirty four men and 127 healthy women were included in the study. Plasma concentrations of IL-18 and leptin were determined in all subjects. Body composition was evaluated by bioelectrical impedanciometry. RESULTS: IL-18 was distributed similarly in men and women and throughout decades. No significant differences were found in IL-18 between obese and normal-weight men and women according to their body mass index and body fat content. Higher IL-18 concentrations were found in subjects with arterial hypertension. In the bivariate correlation analysis only waist to hip ratio correlated weakly with IL-18 in the whole population (r=0.12, p=0.04). In the multiple regression analysis the relationship between IL-18 and waist to hip ratio lost significance after adjusting for age, sex and body mass index. However, IL-18 remained associated with arterial hypertension (adjusted r2=0.25, p=0.023). CONCLUSIONS: The lack of correlation between IL-18 with anthropometric, body composition variables and leptin in our healthy population argues against a role of this cytokine in obesity. Moreover, our findings suggest the implication of this interleukin in the atherogenic process induced by arterial hypertension.

Expression of TWEAK and its receptor Fn14 in human subcutaneous adipose tissue. Relationship with other inflammatory cytokines in obesity.

TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.

Regression of microalbuminuria in type 1 diabetic patients: results of a sequential intervention with improved metabolic control and ACE inhibitors.

The objective was to evaluate the effect of improved metabolic control and ACE inhibition used sequentially in the treatment of type 1 diabetic patients with microalbuminuria. We studied 44 consecutive type 1 diabetic patients with microalbuminuria not previously treated with ACE inhibitors. Improved metabolic control (optimisation period) was attempted for 6-12 months and patients with persistent microalbuminuria were subsequently treated with ACE inhibitors. Stepwise logistic regression analysis included the variables age, age at diabetes onset, duration of diabetes, HbA1c, initial albumin excretion rate (AER) and mean blood pressure as predictors of final AER. Thirty per cent of patients regressed to normoalbuminuria after the optimisation period, and 58% of them maintained normal AER 4.5+/-1.3 years later (3-7 years). Patients achieving normoalbuminuria had lower baseline AER (53+/-22 vs. 94+/-63 mg/24 h, p=0.012). The initial AER level was the only factor associated with final AER (r=0.58, p=0.021). Thirty patients with persistent microalbuminuria were treated with ACE inhibitors for two years, 35.5% of whom regressed to normal AER. Patients achieving normoalbuminuria after ACE inhibitor treatment had lower baseline AER (55+/-24 vs. 132+/-75 mg/24 h, p=0.03). The initial AER was the sole predictor of final AER (r=0.51, p<0.013). Overall, the sequential use of improved metabolic control and ACE inhibitor therapy resulted in long-term normalisation of AER in 47.4% of patients. The sequential implementation of improved metabolic control and ACE inhibitor therapy had a long-term beneficial effect in type 1 diabetic patients with microalbuminuria. We propose that type 1 diabetic patients with microalbuminuria could benefit from a period of metabolic improvement before the initiation of ACE inhibitor therapy.

Streptococcus bovis meningitis in a healthy adult patient.

We describe the first case in the English language of Streptococcus bovis meningitis in a 45-y-old patient without any underlying disease or predisposing condition. S. bovis biotype II was isolated from his spinal fluid and blood. The illness was community-acquired and was clinically and biologically similar to disease caused by the classical meningeal pathogens. The patient was cured after 10 d of therapy with ceftriaxone and, 2.5 y later, is currently healthy. As a result of this case and a similar case published recently in the Spanish literature we conclude that S. bovis should be considered a microorganism capable of causing meningitis in the absence of any underlying condition or clear focus of infection.