Background:
Prospective longitudinal studies evaluating the relevance of “Metabolically Healthy but Obese” (MHO) phenotype at risk for type 2 diabetes mellitus (T2D) and cardiovascular diseases are ...few and results are contradictory.
Methods:
As a representative of the general population, 1051 individuals were evaluated in 1997–1998 and re-evaluated after 6 years and 11 years. Subjects without known T2D were given an oral glucose tolerance test. Anthropometric and biochemical variables were measured. Four sets of criteria were considered to define MHO subjects besides body mass index ≥30 kg/m2: A: Homeostatic Model of Assessment-Insulin Resistance Index (HOMA-IR) <90th percentile; B: HOMA-IR <90th percentile, high-density lipoprotein cholesterol >40 mg/dL in men and high-density lipoprotein cholesterol >50 mg/dL in women, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; C: HOMA-IR <90th percentile, triglycerides <150 mg/dL, fasting glucose <110 mg/dL, and blood pressure ≤140/90 mm Hg; D: HOMA-IR <90th percentile, triglycerides <150 mg/dL, and fasting glucose <110 mg/dL. Subjects with T2D at baseline were excluded from the calculations of incidence of T2D.
Results:
The baseline prevalence of MHO phenotype varied between 3.0% and 16.9%, depending on the set of criteria chosen. Metabolically nonhealthy obese subjects were at highest risk for becoming diabetic after 11 years of follow-up (odds ratio = 8.20; 95% confidence interval = 2.72–24.72; P < .0001). In MHO subjects the risk for becoming diabetic was lower than in metabolically nonhealthy obese subjects, but this risk remained significant (odds ratio = 3.13; 95% confidence interval = 1.07–9.17; P = .02). In subjects who lost weight during the study, the association between MHO phenotype and T2D incidence disappeared, even after adjusting for HOMA-IR.
Conclusions:
The results suggest that MHO is a dynamic concept that should be taken into account over time. As a clinical entity, it may be questionable.
Obesity is characterized by a chronic, low-grade inflammation, and bariatric surgery is proposed as an effective treatment for reducing the obesity-related co-morbidities. Epigenetic modifications ...could be involved in the metabolic improvement after surgery.
The main aim of this study was to evaluate whether DNA methylation pattern from genes related to inflammation and insulin response is associated with the metabolic improvement after bariatric surgery in morbidly obese patients and if these changes depend on the surgical procedure.
University hospital, Spain.
We studied 60 severely obese patients; 31 underwent Roux-en-Y gastric bypass and 29 underwent laparoscopic sleeve gastrectomy. All patients were examined before and at 6 months after bariatric surgery. DNA methylation profile of genes related to the inflammatory response and insulin sensitivity was measured by pyrosequencing.
The promoter methylation levels of the NFKB1 gene were increased significantly after surgery (2.16 ± .9 versus 2.8 ± 1.03). The decrease in blood pressure, both systolic and diastolic, after surgery was significantly associated with the changes in the promoter methylation levels of the NFKB1 gene (β = -.513, P = .003 and β = -.543, P = .004, respectively). A decrease in inflammation status, measured by high sensitivity C-reactive protein values, was associated with changes in SLC19A1 methylation levels.
Our study shows for the first time an association between NFKB1 methylation levels and blood pressure after bariatric surgery, highlighting the possible function of this gene in the regulation of arterial pressure. Regarding SLC19A1, this gene could position as a potential target linking inflammation and insulin resistance.
Objective
To analyze the reference range of thyroid‐stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism.
Methods
The study included 3,928 ...individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH <10 µUI/mL and thyroid peroxidase antibodies TPO Abs <50 IU/mL) who participated in a national, cross‐sectional, population‐based study and were representative of the adult population of Spain. Data gathered included clinical and demographic characteristics, physical examination, and blood and urine sampling. TSH, free thyroxine, free triiodothyronine, and TPO Ab were analyzed by electrochemiluminescence (E170, Roche Diagnostics, Basel, Switzerland).
Results
The reference range (p2.5‐97.5) for TSH was estimated as 0.6 to 4.8 µUI/mL in the underweight category (BMI<20 kg/m2), 0.6 to 5.5 µUI/mL in the normal‐weight category (BMI 20‐24.9 kg/m2), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25‐29.9 kg/m2), 0.5 to 5.9 µUI/mL in the obesity category (BMI 30‐39.9 kg/m2), and 0.7 to 7.5 µUI/mL in the morbid obesity category (BMI ≥40). By using the reference criteria for the normal‐weight population, the prevalence of high TSH levels increased threefold in the morbid obesity category (P < 0.01).
Conclusions
Persons with morbid obesity might be inappropriately classified if the standard ranges of normality of TSH for the normal‐weight population are applied to them.
Summary Background & aims Oxidative stress is believed to play an important role in the pathophysiology of bronchiectasis. The aims of this study were to evaluate the oxidative stress status in ...bronchiectasis patients. Methods This cross-sectional study included 90 clinically stable adults with bronchiectasis of any aetiology (36 with cystic fibrosis CF and 54 without CF) plus 50 healthy controls. Plasma and serum oxidative stress biomarkers were measured using commercial kits. Cellular oxidative stress biomarkers in white blood cells (mitochondrial membrane potential, intracellular glutathione, superoxide anion and hydrogen peroxide) were analyzed by flow cytometry. Results Compared with the control group, the catalase activity and lipid peroxidation (TBARs and 8-isoprostanes) were significantly increased in the patient group and the total antioxidant capacity and the activity of superoxide dismutase were decreased. Intracellular superoxide anion and hydrogen peroxide were significantly elevated in the patients versus the controls in total leukocytes, lymphocytes, monocytes and neutrophils. Compared to the controls, the mitochondrial membrane potential was significantly lower in neutrophils and intracellular glutathione in monocytes. No significant differences were observed between CF and non-CF bronchiectasis patients in the oxidative stress biomarkers studied. Conclusions Biomarkers of oxidative stress, both in plasma and intracellular were raised in patients with bronchiectasis compared with controls. No differences were seen in the CF patients compared with the others.
Purpose
This study examines whether G-protein coupled receptor 120 (GPR120) is involved in the pro-/anti-inflammatory effects of different types of fatty acids (FAs) in human visceral adipocytes, and ...whether these effects may be altered in obesity, a state with a chronic inflammation.
Methods
Pro-/anti-inflammatory effects of palmitic, oleic, linoleic and docosahexaenoic acids on human visceral adipocytes were tested in mature adipocytes from non-obese and morbidly obese (MO) subjects. Also, the effects of these FAs were tested when the GPR120 gene was silenced.
Results
In adipocytes from non-obese subjects, palmitic and linoleic acids increased TNF-α and IL-6 mRNA expression (
p
< 0.05), and decreased IL-10 and adiponectin expression (
p
< 0.05). However, oleic and docosahexaenoic acids (DHA) produced the opposite effect (
p
< 0.05). In adipocytes from MO subjects, all FAs used increased TNF-α and IL-6 expression (
p
< 0.05). Palmitic and linoleic acids decreased IL-10 and adiponectin expression (
p
< 0.05), but oleic acid and DHA did not have significant effects. Only oleic acid increased adiponectin expression (
p
< 0.05). The effects of FAs on TNF-α, IL-6, IL-10 and adiponectin expression in non-obese and MO subjects were significantly annulled when the GPR120 gene was silenced in visceral adipocytes differentiated from human mesenchymal stem cells.
Conclusions
FAs are capable of directly acting on visceral adipocytes to modulate differently TNF-α, IL-6, IL-10 and adiponectin expression, with a different and greater effect in MO subjects. These effects are largely annulled when GPR120 expression was silenced, which suggests that they could be mediated by GPR120.
•The scientific question asked: Is iodine intake related to male infertility, independently of thyroid hormones?.•The principal new findings: Men with higher semen iodine levels had more ...morphological alteration in spermatozoa. Men with higher urinary iodine had a lower motile sperm count.•The significance of these findings to the field: This study brings a new approach to the study of infertile couples. The cause-effect relationship needs to be explored further in other type of study.
The role that adequate iodine intake could have on the male reproductive function is not entirely known. The aim of this study is to determine whether there is a relation between male infertility and urinary and semen iodine levels in 96 couples who underwent consultation for infertility. The median of semen iodine was higher in men who consumed iodized salt than in those who consumed non-iodized salt (p=0.019). Men with a higher semen iodine level had more morphological alterations in spermatozoa (p=0.032). Men with a higher urinary iodine level had a lower motile sperm count according to the “direct swim-up” technique (p=0.044). Men >3years without successfully achieving pregnancy had a higher urinary iodine level than those with ≤ 3years (p=0.035). In conclusion, iodine may play a role in the quality of semen: an increase in semen iodine levels is associated with different variables related to male infertility.
Obesity is a complex disease that has a strong association with diet and lifestyle. Dietary factors can influence the expression of key genes connected to insulin resistance, lipid metabolism, and ...adipose tissue composition. In this study, our objective was to determine gene expression and fatty acid (FA) profiles in visceral adipose tissue (VAT) from lean and morbidly obese individuals. We also aimed to study the agonist effect of dietary factors on glucose metabolism.
Lean and low and high insulin resistance morbidly obese subjects (LIR-MO and HIR-MO) were included in this study. The gene expression of liver X receptor type alpha (LXR-α) and glucose transporter type 4 (GLUT4) and the FA profiles in VAT were determined. Additionally, the in vivo and in vitro agonist effects of oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) by peroxisome proliferator-activated receptor type gamma 2 (PPAR-γ2) on the activity of GLUT4 were studied.
Our results showed a dysregulation of GLUT4 and LXR-α in VAT of morbidly obese subjects. In addition, a specific FA profile for morbidly obese individuals was found. Finally, AA was an PPAR-γ2 agonist that activates the expression of GLUT4.
Our study suggests a dysregulation of LXR-α and GLUT4 expression in VAT of morbidly obese individuals. FA profiles in VAT could elucidate their possible role in lipolysis and adipogenesis. Finally, AA binds to PPAR-γ2 to activate the expression of GLUT4 in the HepG2 cell line, showing an alternative insulin-independent activation of GLUT4.
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher ...number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from H
S and NH
. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.
Introduction
This study evaluates the effects of 25 mL of three types of oils extra‐virgin olive oil (EVOO), olive oil (OO), and sunflower oil (SO) on postprandial (3 h) satiety markers and variables ...related to metabolic status and inflammation in non‐obese patients (n = 6) and in those with morbid obesity (n = 6), before and 1 year after Roux‐en‐Y gastric by‐pass (RYGB).
Methods and Results
After EVOO intake, serum acylated ghrelin decreases and GLP1 increases more than with OO and SO. EVOO causes a higher increase of insulin and lower postprandial hypertriglyceridemia and free fatty acid levels than with OO and SO. EVOO decreases TNFα and IL6 expression in peripheral blood mononuclear cells, with OO inducing intermediate effects and SO inducing an increase of these proinflammatory markers. These results are observed in non‐obese patients and in those with morbid obesity after RYGB. However, patients with morbid obesity before RYGB show a profound alteration of this response.
Conclusion
EVOO produces more beneficial effects than OO, which has lower amounts of minor components, and SO, which has PUFA as its main component. RYGB produces an improvement in the metabolic response to all three types of oils in patients with morbid obesity.
Extra‐virgin olive oil produces more beneficial effects than olive oil, which has lower amounts of minor components, and sunflower oil, which has polyunsaturated fatty acids as its main component. These results are observed in non‐obese patients and in those with morbid obesity after bariatric surgery. However, patients with morbid obesity before bariatric surgery show a profound alteration of this response.
FNDC5 could be regulated by leptin in adipose tissue Gutierrez-Repiso, Carolina; Garcia-Serrano, Sara; Rodriguez-Pacheco, Francisca ...
European journal of clinical investigation,
October 2014, Letnik:
44, Številka:
10
Journal Article
Recenzirano
Introduction
Irisin activates the thermogenic function in adipose tissues. However, little is known on the association between human irisin and different cardiometabolic risk factors. We analyse the ...influence of morbid obesity on irisin levels and its relation with leptin and different cardiovascular risk factors.
Material and methods
We measured the serum irisin level and the fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue from 33 morbidly obese subjects and 12 nonobese subjects. We also studied the effect of leptin on FNDC5 expression.
Results
Serum irisin was higher in the nonobese subjects than in morbidly obese subjects, both before (P = 0·043) and after bariatric surgery (P = 0·042). The variable that best explained the serum irisin levels in a multiple linear regression model was the waist‐to‐hip ratio (WHR) (R2 = 0·201) (Beta = −0·357, P = 0·046). Those morbidly obese subjects with android‐type obesity had lower serum irisin levels than those with gynecoid‐type obesity, both before (P = 0·027) and after bariatric surgery (P = 0·006). Only the percentage change in WHR was associated with serum irisin levels after bariatric surgery (r = −0·529, P = 0·005). FNDC5 expression levels in subcutaneous adipose tissue (SAT) were higher in the nonobese than in the morbidly obese subjects (P = 0·042). In SAT explants from nonobese subjects, leptin (20 and 150 ng/mL) produced a decrease in FNDC5 expression (P = 0·009 and P = 0·037, respectively).
Conclusions
We showed decreased serum irisin levels in morbidly obese subjects, related mainly to WHR. FNDC5 expression could be regulated by leptin.
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