Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

Abstract Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats

Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity.

Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance

[EN] To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin signalling and signal transducer and activator of transcription 3 (STAT3) phosphorylation and reduce AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) phosphorylation. Deltoid and vastus lateralis muscle biopsies were obtained from 20 men: 10 non-obese control subjects (mean +/- s.d. age, 31 +/- 5 years; height, 184 +/- 9 cm; weight, 91 +/- 13 kg; and percentage body fat, 24.8 +/- 5.8%) and 10 obese (age, 30 +/- 7 years; height, 184 +/- 8 cm; weight, 115 +/- 8 kg; and percentage body fat, 34.9 +/- 5.1%). Skeletal muscle OB-R170 (OB-R long isoform) protein expression was 28 and 25% lower (both P < 0.05) in arm and leg muscles, respectively, of obese men compared with control subjects. In normal-weight subjects, SOCS3 protein expression, and STAT3, AMPKalpha and ACCbeta phosphorylation, were similar in the deltoid and vastus lateralis muscles. In obese subjects, the deltoid muscle had a greater amount of leptin receptors than the vastus lateralis, whilst SOCS3 protein expression was increased and basal STAT3, AMPKalpha and ACCbeta phosphorylation levels were reduced in the vastus lateralis compared with the deltoid muscle (all P < 0.05). In summary, skeletal muscle leptin receptors and leptin signalling are reduced in obesity, particularly in the leg muscles.

Characterization of circulating steroids and endocannabinoids levels in obese subjects by liquid chromatography tandem mass spectrometry

Nowadays obesity can be defined as a global epidemic. The precise identification of circulating biomarkers involved in this pathology could be essential to early diagnose potential co-morbidities and to better address the development of future therapeutic strategies. Published evidences show that circulating steroid hormones and endocannabinoids might have a role in the physiopathology of obesity; however, a precise and reliable quantification of these molecules is still lacking. In the first part of the present thesis, we developed a sensitive, specific and accurate quantification method for nine steroid hormones using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. This method has been used first for a comparative study with immunoassays, currently used in the clinical practice to quantify these molecules and then to redefine circulating reference intervals in healthy subjects. Furthermore, we measured circulating steroid hormones in three groups of subjects: normo-weight, over-weight and obese, defining different steroid hormones profiles depending on the obesity state. The role of circulating endocannabinoids in humans is still unclear, however there are several evidences concerning their involvement in obesity. In the second part of the thesis, we determined changes of circulating endocannabinoids in obese patients after a weight loss induced by bariatric surgery, currently the most effective long-term treatment for obesity, using LC/MS-MS. We measured basal and dynamic endocannabinoids plasma levels in 12 patients with severe obesity before, one month after and six months after the Roux-en-Y gastric bypass intervention, currently one of the most performed types of bariatric surgery. All together the findings illustrated in this thesis project will help better define the role of steroid hormones and endocannabinoids in the framework of obesity in humans and the role that each type of molecule might have in its pathophysiology.

The relationship between eating behavior and psychological distress among overweight and obese people: is there a role for mindfulness?

This research based on 3 indipendent studies, sought to explore the nature of the relationship between overweight/obesity, eating behaviors and psychological distress; the construct of Mindful eating trough the validation of the Italian adaptation of the Mindful Eating Questionnaire (MEQ); the role of mindfulnessand mindful eating as respectively potential mediator and moderator between overeating behavior (binge eating and emotional overeating) and negative outcomes (psychological distress, body dissatisfaction). All the samples were divided in normal weight, overweight and obese according to BMI categories. STUDY1: In a sample of 691 subjects (69.6% female, mean aged 39.26 years) was found that BMI was not associated with psychological distress, whereas binge eating increases the psychopathological level. BMI and male gender represent negative predictors of psychological distress, but certain types of overeating (i.e., NES/grazing, overeating during or out of meals, and guilt/restraint) result as positive predictors.. STUDY 2 : A sample of 1067 subjects (61.4% female, mean aged 34 years) was analized. The Italian MEQ resulted in a 26-item 4-factor model measuring Disinhibition, Awareness, Distraction, and Emotional response. Internal consistency and test-retest reliability were acceptable MEQ correlated positively with mindfulness (FMI) and it was associated with sociodemographic variables, BMI, meditation. type of exercise and diet. STUDY 3, based on a sample of 502 subjects (68.8% female, mean aged 39.42 years) showed that MEQ and FMI negatively correlated with BES, EOQ, SCL-90-R, and BIAQ. Obese people showed lower level of mindful eating and higher levels of binge eating, emotional overeating, and body dissatisfaction, compared to the other groups Mindfulness resulted to partially mediates the relationship between a) binge eating and psychological distress, b) emotional overeating and psychological distress, c) binge eating and mental well-being, d) emotional overeating and menal well-being. Mindful eating was a moderator only in the relationship between emotional overeating and body dissatisfaction.

Regulation of wingless-type MMTV integration site family (WNT) signalling in pancreatic islets from wild-type and obese mice

TCF7L2 is a type 2 diabetes susceptibility gene and downstream effector of canonical wingless-type MMTV integration site family (WNT) signalling. However, it is unknown whether this pathway is active in adult pancreatic islets in vivo, and whether it is regulated in obesity.

Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients

High protein diets have been shown to improve hepatic steatosis in rodent models and in high-fat fed humans. We therefore evaluated the effects of a protein supplementation on intrahepatocellular lipids (IHCL), and fasting plasma triglycerides in obese non diabetic women.

Decreased Detection of Hypovascular Liver Tumors With MDCT in Obese Patients: A Phantom Study

The purpose of this article is to assess the impact of large patient size on the detection of hypovascular liver tumors with MDCT and the effect of a noise filter on image quality and lesion detection in obese patients.

Effects of a 2-y dietary weight-loss intervention on cholesterol metabolism in moderately obese men

Long-term dietary weight loss results in complex metabolic changes. However, its effect on cholesterol metabolism in obese subjects is still unclear.

Effects of Aerobic Versus Resistance Exercise Without Caloric Restriction on Abdominal Fat, Intrahepatic Lipid, and Insulin Sensitivity in Obese Adolescent Boys: A Randomized, Controlled Trial

The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and secretion in youth. Forty-five obese adolescent boys were randomly assigned to one of three 3-month interventions: AE, RE, or a nonexercising control. Abdominal fat was assessed by magnetic resonance imaging, and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy. Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp. Both AE and RE prevented the significant weight gain that was observed in controls. Compared with controls, significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups. Compared with controls, a significant improvement in insulin sensitivity (27%) was observed in the RE group. Collapsed across groups, changes in visceral fat were associated with changes in intrahepatic lipid (r = 0.72) and insulin sensitivity (r = -0.47). Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys. RE but not AE is also associated with significant improvements in insulin sensitivity.

Chitinase expression in parotid glands of non-obese diabetic mice

OBJECTIVE: This investigation was a basal study that used a mouse model of xerostomia to identify protein biomarkers of xerostomia in saliva. We identified genes expressed differently in parotid glands from non-obese diabetic mice with diabetes and those from control mice; subsequently, we investigated expression of the proteins encoded by these genes in parotid glands and saliva. MATERIALS AND METHODS: DNA microarray and real-time PCR analyses were performed to detect differences between NOD/ShiJcl and C57BL/6JJcl (control) female mice in gene expression from parotid glands or parotid acinar cells. Subsequently, protein expression was assessed using immunoblotting and immunohistochemistry. Similarly, enzyme activity in saliva was assessed using zymography. RESULTS: Based on gene expression analyses, Chia expression was higher in diabetic mice than non-diabetic mice and control mice; similarly, expression of chitinase, the protein encoded by Chia, was higher in diabetic mice. Saliva from NOD/ShiJcl mice had more chitinase than saliva from control mice. CONCLUSIONS: Chitinase was highly expressed in parotid acinar cells from diabetic mice compared with non-diabetic and control mice. Increased chitinase expression and enzyme activity may characterize the autoimmune diabetes in mice; however, further investigation is required to assess its use as a biomarker of xerostomia in humans.

Subcutaneous oxygen pressure in spontaneously breathing lean and obese volunteers: a pilot study

BACKGROUND: Oxidative killing is the primary defense against surgical pathogens; risk of infection is inversely related to tissue oxygenation. Subcutaneous tissue oxygenation in obese patients is significantly less than in lean patients during general anesthesia. However, it remains unknown whether reduced intraoperative tissue oxygenation in obese patients results from obesity per se or from a combination of anesthesia and surgery. In a pilot study, we tested the hypothesis that tissue oxygenation is reduced in spontaneously breathing, unanesthetized obese volunteers. METHODS: Seven lean volunteers with a body mass index (BMI) of 22 +/- 2 kg/m(2) were compared to seven volunteers with a BMI of 46 +/- 4 kg/m(2). Volunteers were subjected to the following oxygen challenges: (1) room air; (2) 2 l/min oxygen via nasal prongs, (3) 6 l/min oxygen through a rebreathing face mask; (4) oxygen as needed to achieve an arterial oxygen pressure (arterial pO(2)) of 200 mmHg; and (5) oxygen as needed to achieve an arterial pO(2) of 300 mmHg. The oxygen challenges were randomized. Arterial pO(2) was measured with a continuous intraarterial blood gas analyzer (Paratrend 7); deltoid subcutaneous tissue oxygenation was measured with a polarographic microoxygen sensor (Licox). RESULTS: Subcutaneous tissue oxygenation was similar in lean and obese volunteers: (1) room air, 52 +/- 10 vs 58 +/- 8 mmHg; (2) 2 l/min, 77 +/- 25 vs 79 +/- 24 mmHg; (3) 6 l/min, 125 +/- 43 vs 121 +/- 25 mmHg; (4) arterial pO(2) = 200 mmHg, 115 +/- 42 vs 144 +/- 23 mmHg; (5) arterial pO(2) = 300 mmHg, 145 +/- 41 vs 154 +/- 32 mmHg. CONCLUSION: In this pilot study, we could not identify significant differences in deltoid subcutaneous tissue oxygen pressure between lean and morbidly obese volunteers.

Abdominal multislice CT for obese patients: effect on image quality and radiation dose in a phantom study

RATIONALE AND OBJECTIVES: To evaluate the effect of a modified abdominal multislice computed tomography (CT) protocol for obese patients on image quality and radiation dose. MATERIALS AND METHODS: An adult female anthropomorphic phantom was used to simulate obese patients by adding one or two 4-cm circumferential layers of fat-equivalent material to the abdominal portion. The phantom was scanned with a subcutaneous fat thickness of 0, 4, and 8 cm using the following parameters (detector configuration/beam pitch/table feed per rotation/gantry rotation time/kV/mA): standard protocol A: 16 x 0.625 mm/1.75/17.5 mm/0.5 seconds/140/380, and modified protocol B: 16 x 1.25 mm/1.375/27.5 mm/1.0 seconds/140/380. Radiation doses to six abdominal organs and the skin, image noise values, and contrast-to-noise ratios (CNRs) were analyzed. Statistical analysis included analysis of variance, Wilcoxon rank sum, and Student's t-test (P < .05). RESULTS: Applying the modified protocol B with one or two fat rings, the image noise decreased significantly (P < .05), and simultaneously, the CNR increased significantly compared with protocol A (P < .05). Organ doses significantly increased, up to 54.7%, comparing modified protocol B with one fat ring to the routine protocol A with no fat rings (P < .05). However, no significant change in organ dose was seen for protocol B with two fat rings compared with protocol A without fat rings (range -2.1% to 8.1%) (P > .05). CONCLUSIONS: Using a modified abdominal multislice CT protocol for obese patients with 8 cm or more of subcutaneous fat, image quality can be substantially improved without a significant increase in radiation dose to the abdominal organs.