Highlights • The link between orexin-A and sleep in anorexia nervosa has not been explored. • Anorexia nervosa patients reported overall poorer sleep versus healthy controls. • No differences were ...found between the patients and healthy controls in orexin-A. • Orexin-A concentrations and poorer sleep were related. • High orexin-A levels and inefficient sleep contributed to poor treatment outcome.
Lactoferrin is an innate immune system protein with anti-inflammatory and antioxidant activities. We aimed to evaluate circulating lactoferrin levels in association with lipid concentrations, and ...parameters of oxidative stress and inflammation in subjects with morbid obesity after an acute fat intake. The effects of a 60 g fat overload on circulating lactoferrin and antioxidant activities were evaluated in 45 severely obese patients (15 men and 30 women, BMI 53.4 ± 7.2 kg/m2). The change in circulating lactoferrin after fat overload was significantly and inversely associated with the free fatty acid (FFA) change. In those subjects with the highest increase in lactoferrin (in the highest quartile), high-density lipoprotein (HDL)-cholesterol decreased after fat overload to a lesser extent (P = 0.03). In parallel to lipid changes, circulating lactoferrin concentrations were inversely linked to the variations in catalase (CAT) and glutathione reductase (GSH-Rd). Baseline circulating lactoferrin concentration was also inversely associated with the absolute change in antioxidant activity after fat overload, and with the change in C-reactive protein (CRP). Furthermore, those subjects with higher than the median value of homeostasis model assessment of insulin secretion (HOMAIS) had significantly increased lactoferrin concentration after fat load (885 ± 262 vs. 700 ± 286 ng/ml, P = 0.03). Finally, we further explored the action of lactoferrin in vitro. Lactoferrin (10 µmol/l) led to significantly lower triglyceride (TG) concentrations and lactate dehydrogenase activity (as expression of cell viability) in the media from adipose explants obtained from severely obese subjects. In conclusion, circulating lactoferrin concentrations, both at baseline and fat-stimulated, were inversely associated with postprandial lipemia, and parameters of oxidative stress and fat-induced inflammation in severely obese subjects.
Protein expression studies based on the two major intra-abdominal human fat depots, the subcutaneous and the omental fat, can shed light into the mechanisms involved in obesity and its ...co-morbidities. Here we address, for the first time, the identification and validation of reference proteins for data standardization, which are essential for accurate comparison of protein levels in expression studies based on fat from obese and non-obese individuals.
To uncover adipose tissue proteins equally expressed either in omental and subcutaneous fat depots (study 1) or in omental fat from non-obese and obese individuals (study 2), we have reanalyzed our previously published data based on two-dimensional fluorescence difference gel electrophoresis. Twenty-four proteins (12 in study 1 and 12 in study 2) with similar expression levels in all conditions tested were selected and identified by mass spectrometry. Immunoblotting analysis was used to confirm in adipose tissue the expression pattern of the potential reference proteins and three proteins were validated: PARK7, ENOA and FAA. Western Blot analysis was also used to test customary loading control proteins. ENOA, PARK7 and the customary loading control protein Beta-actin showed steady expression profiles in fat from non-obese and obese individuals, whilst FAA maintained steady expression levels across paired omental and subcutaneous fat samples.
ENOA, PARK7 and Beta-actin are proper reference standards in obesity studies based on omental fat, whilst FAA is the best loading control for the comparative analysis of omental and subcutaneous adipose tissues either in obese and non-obese subjects. Neither customary loading control proteins GAPDH and TBB5 nor CALX are adequate standards in differential expression studies on adipose tissue. The use of the proposed reference proteins will facilitate the adequate analysis of proteins differentially expressed in the context of obesity, an aim difficult to achieve before this study.
Context:
Betatrophin is produced primarily by liver and adipose tissue and has been recently reported as a novel hormone promoting β-cell proliferation and β-cell mass and improving glucose ...tolerance.
Objective:
Because it is markedly regulated by nutritional status, we hypothesized that circulating betatrophin levels might be affected by pathophysiological conditions altering body weight.
Setting and Patients:
We analyzed circulating betatrophin levels in 149 female patients, including 99 with extreme body mass index (30 anorexia nervosa, 24 obese, 45 morbid obese, and 50 healthy eating/weight controls).
Outcome Measurements:
Serum betatrophin levels and its correlations with different anthropometric and biochemical parameters were measured.
Results:
Plasma betatrophin levels were significantly elevated in anorexic patients, whereas its levels were reduced in morbidly obese women when compared with normal-weight women. Plasma betatrophin correlated negatively with weight, body mass index, fat percentage, glucose, insulin, and homeostatic model assessment index and positively correlated with high-density lipoprotein.
Conclusions:
These results suggest that metabolic status is an important regulator of circulating betatrophin levels.
BackgroundAcute phase mediators promote metabolic changes by modifying circulating hormones. However, there is virtually no data about the link between glucagon and inflammatory parameters in ...obesity-related chronic low-grade inflammation.Study designWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating glucagon concentrations (ELISA), parameters of glucose and lipid metabolism, interleukin 6 (IL6), and complement factor B (CFB) were analyzed in 316 subjects (250 men and 66 women). The effects of weight loss were investigated in an independent cohort of 20 subjects.ResultsCirculating glucagon significantly correlated with glucose (r=0.407, P<0.0001), HbAlc (r=0.426, P<0.0001), fasting triglycerides (r=0.356, P=0.001), and parameters of innate immune response system such as IL6 (r=0.342, P=0.050) and CFB (r=0.404, P=0.002) in obese subjects with altered glucose tolerance, but not in individuals with normal glucose tolerance (NGT). In obese and NGT subjects, glucagon was associated with fasting triglycerides (r=0.475, P=0.003) and CFB (r=0.624, P=0.001). In obese subjects, glucagon (P=0.019) and CFB (P=0.002) independently contributed to 26% of fasting triglyceride variance (P<0.0001) after controlling for the effects of age and fasting serum glucose concentration in multiple lineal regression models. Moreover, concomitant with fat mass, fasting triglycerides, and CFB, weight loss led to significantly decreased circulating glucagon (−23.1%, P=0.004).ConclusionsAccording to the current results, acute phase reactants such as IL6 and CFB are associated with fasting glucagon in metabolically compromised subjects. This suggests that glucagon may be behind the association between inflammatory and metabolic parameters in obesity-associated chronic low-grade inflammation.
(1) The objective of this study is to analyze differences in smell–taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste ...capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC 64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls. Smell and taste assessments were performed through “Sniffin’ Sticks” and “Taste Strips,” respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract Ghrelin, peptide YY, cholecystokinin. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.
Anorexia nervosa (AN) is a severe eating disorder accompanied by alterations in endocrinological circuits and deficits in neuropsychological performance. In this study, a series of ...appetite-regulating hormones (ghrelin, leptin, cholecystokinin, PYY, adiponectin, and visfatin) were measured under fasting conditions in female patients with AN and female healthy controls. All of the participants also underwent a battery of neuropsychological assessment namely the Iowa Gambling Task (IGT), the Wisconsin Card Sorting Test (WCST), and the Stroop Color and Word Test (SCWT). As the main finding, we found that higher ghrelin levels predict better performance in the IGT. Ghrelin may be a putative mediator of decision-making, a finding that has not been described so far. The role of ghrelin in decision-making can only be described as speculative, as there are hardly any additional evidence-based data published up to date. Further studies are warranted.
•There is evidence for deficits in decision-making as assessed in the Iowa Gambling Task (IGT) in Anorexia Nervosa (AN).•Ghrelin is increased in underweight patients with AN and tends to normalize parallel to weight increase.•There is hardly evidence associating neuropsychological performance in AN with appetite-regulating hormones.•Here, higher ghrelin concentrations were associated with better performance (IGT), considering patients with AN and controls.•Ghrelin-mediated signaling may play an important part in cognitive performance.
Objective To explore the relationship between iron and infertility by investigating iron-related gene expression in granulosa and uterine cervical cells. Design Case-control study. Setting Two ...tertiary hospitals. Patient(s) Two independent cohorts of fertile (n = 18 and n = 17) and infertile (n = 31 and n = 35) women. Intervention(s) In vitro fertilization. Main Outcome Measure(s) Gene expression levels of ferritin light chain ( FTL ), ferritin heavy chain ( FTH ), transferrin receptor ( TFRC ), and ferroportin ( SLC40A1 ) mRNA were analyzed in granulosa and cervical cells. Result(s) In the first cohort, fertile and infertile women were similar in body mass index. Ferroportin mRNA levels were decreased in granulosa cells from infertile women in parallel with increased serum hepcidin levels. A positive association between ferroportin and TFRC mRNA, a gene associated with intracellular iron deficiency, was observed only in granulosa cells from fertile women. The major findings were replicated in a second independent cohort. Conclusion(s) Ferroportin mRNAs and circulating hepcidin identify a subset of infertile women and may constitute a target for therapy.
Context:
The relationship between 25-hydroxyvitamin D 25(OH)D and obesity and type 2 diabetes is not completely understood. Vitamin D receptor (VDR) expression in adipose tissue (AT) is related to ...obesity and might be regulated by 1,25-dihydroxyvitamin D3 1,25(OH)2D3.
Objective:
To analyze serum 25(OH)D and VDR gene expression in AT according to body mass index (BMI) and glycemic status and the effect of 1,25(OH)2D3 on AT according to BMI.
Design and Patients:
Two cohorts were studied: 1) 118 subjects classified according to their BMI (lean, overweight, obese, or morbidly obese MO) and their glycemic status (normoglycemic NG and prediabetic and diabetic P&D); and 2) 30 obese subjects (BMI > 30 kg/m2) classified as NG and P&D. VDR gene expression was analyzed during preadipocyte differentiation and in vitro stimulation with 1,25(OH)2D3 of AT explants from donors with different BMI values.
Setting:
University Hospital.
Main Outcome Measures:
Serum 25(OH)D, parathyroid hormone (PTH), and AT VDR gene expression.
Results:
25(OH)D levels were lower in P&D than NG subjects, significantly so in the lean and MO groups (P < .05). 25(OH)D levels correlated negatively with homeostasis model of assessment for insulin resistance (HOMA-IR) (r = −0.200; P = .032) and glucose (r = −0.295; P = .001), but not with BMI. VDR gene expression was higher in MO than in the other BMI groups (P < .05). 1,25(OH)2D3 increased VDR gene expression in AT from obese patients (P < .05) but not from lean subjects.
Conclusions:
25(OH)D levels are diminished in P&D compared to NG subjects, independently of BMI, and are closely related to glucose metabolism variables, suggesting that vitamin D deficiency is associated more with carbohydrate metabolism than with obesity. Moreover, AT has a different response to 1,25(OH)2D3 depending on the degree of obesity.
Context: Two adipokines highly expressed in fat mass, adiponectin with antiinflammatory and antiatherogenic properties and visfatin with an insulin-mimetic effect, are potential contributors to bone ...metabolism. In acromegaly, data on adiponectin are contradictory, and there are no data on visfatin.
Objectives: The aim of the study was to evaluate adiponectin and visfatin in acromegaly, compared to control subjects, and to analyze their relationship with body composition and bone markers.
Methods: Bone markers osteocalcin, total amino-terminal propeptide of type 1 procollagen (total P1NP), carboxy-terminal telopeptide (β-Crosslaps), body composition (by dual-energy x-ray absorptiometry), adiponectin (by ELISA), and visfatin (by immunoanalysis) were evaluated in 60 acromegalic patients (24 males and 36 females) and in 105 age- and gender-matched healthy controls (33 males and 72 females). Acromegalic patients were classified as controlled, with normal IGF-I and nadir GH no greater than 1 μg/liter (n = 41), or active (n = 19).
Results: Acromegalic patients had lower adiponectin (P < 0.01), more lean body mass (P < 0.01), more total body mass (P < 0.01), higher bone formation markers (osteocalcin and total P1NP, P < 0.05 and P < 0.01, respectively), but less bone resorption markers (β-Crosslaps, P < 0.001) than controls. No differences in visfatin and BMD were found between patients and controls. Adiponectin correlated negatively with BMD (r = −0.374; P < 0.05) and lean mass (r = −0.301; P < 0.05) and positively with age (r = 0.341; P < 0.001) in acromegaly. Visfatin correlated negatively with BMD (r = −0.359; P < 0.05). BMD was the predictor for adiponectin and visfatin.
Conclusions: Acromegalic patients present hypoadiponectinemia and a favorable bone marker profile. Adiponectin and visfatin could be a link between fat mass and bone in acromegaly.
Bone mineral density is correlated negatively with, and is a predictor for, adiponectin and visfatin in patients with acromegaly.
PDF
