Adipose tissue secretion and expression of adipocyte-produced and stromavascular fraction-produced adipokines vary during multiple phases of weight-reducing dietary intervention in obese women.

CONTEXT: Obesity is associated with altered plasma levels of adipokines involved in the development of insulin resistance and obesity-related metabolic disturbances. OBJECTIVE: The aim was to investigate diet-induced changes in adipokine production in sc abdominal adipose tissue (SAT) during a 6-month, multiphase, weight-reducing dietary intervention. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Forty-eight obese women followed a dietary intervention consisting of a very low-calorie diet (VLCD) (1 month), followed by a weight-stabilization (WS) period, which consisted of a low-calorie diet (2 months), and a weight-maintenance diet (3 months). MAIN OUTCOME MEASURES: Before and at the end of the VLCD and WS, samples of plasma and SAT were obtained. In a subgroup of 26 women, secretion of adipokines was determined in SAT explants, and in a subgroup of 22 women, SAT mRNA expression was measured. RESULTS: Body weight decreased and insulin sensitivity increased during the intervention. Plasma levels, SAT mRNA expression, and secretion rates of adipocyte-produced adipokines (leptin, serum amyloid A, and haptoglobin) decreased during the VLCD and increased during the WS period. Adipokines produced mainly from stroma-vascular cells (IL-6, IL-8, IL-10, IL-1Ra, TNFα, plasminogen activator inhibitor-1, and monocyte chemoattractant protein-1) increased or remained unchanged during VLCD and decreased to levels equal to or lower than prediet levels during the WS period. The diet-induced changes in homeostasis model assessment of insulin resistance correlated with changes in leptin plasma levels during VLCD, WS, and the entire dietary intervention period. CONCLUSIONS: Diet-induced regulation of adipokine production in SAT differs according to their cellular origin (adipocytes vs. stroma-vascular cells) and diet phase (VLCD vs. WS). Insulin-sensitivity changes were associated only with those of plasma leptin.

Application of the Theory of Planned Behaviour to weight control in an overweight cohort. Results from a pan-European dietary intervention trial (DiOGenes).

Using the Theory of Planned Behaviour (TPB), this study investigates weight control in overweight and obese participants (27 kg/m(2)≤BMI<45 kg/m(2)) taking part in a dietary intervention trial targeted at weight loss maintenance (n=932). Respondents completed TPB measures investigating "weight gain prevention" at three time points. Correlation and regression analyses were used to investigate the relationship between TPB variables and weight regain. The TPB explained up to 27% variance in expectation, 14% in intention and 20% in desire scores. No relationship was established between intention, expectation or desire and behaviour at Time 1 or Time 2. Perceived need and subjective norm were found to be significantly related to weight regain, however, the model explained a maximum of 11% of the variation in weight regain. Better understanding of overweight individuals' trajectories of weight control is needed to help inform studies investigating people's weight regain behaviours. Future research using the TPB model to explain weight control should consider the likely behaviours being sought by individuals.

Post-prandial endothelial dysfunction is ameliorated following weight loss in obese premenopausal women.

BACKGROUND: Endothelial dysfunction and postprandial hyperglycemia represent independent risk factors for cardiovascular diseases. Obesity is connected with endothelial impairments; however, it is unclear whether weight loss can modify endothelial function during the postprandial period. The aim of this study was to evaluate endothelial response (post-ischemic forearm blood flow, PIFBF) in a fasted state and following ingestion of 75 g glucose before and after very low caloric diet (VLCD). MATERIAL/METHODS: 40 obese premenopausal women (age 39.6 ± 7.8 years, BMI 34.3 ± 3.2 kg/m2) participated in 4-week very low caloric diet (VLCD, 800 kcal/day). Before and after VLCD, the baseline blood flow and PIFBF were measured using a mercury strain gauge plethysmography in fasting state as well as 1 hour after ingestion of 75 g glucose. RESULTS: Dietary intervention resulted in a 7% weight loss (p<0.05) and a decrease in insulin resistance index HOMA-IR (2.44 ± 1.25 vs. 1.66 ± 0.81, p<0.05). Before VLCD intervention, PIFBF following oral glucose challenge decreased by 8.2 ± 9.1 ml/min/100 g tissue, while after weight loss identical stimulus increased PIFBF by 4.2 ± 8.9 ml/min/100 g tissue (p<0.05). Plasma ICAM-1 and VCAM-1 decreased by 8% and 10%, respectively, throughout the study. CONCLUSIONS: Postprandial endothelial dysfunction is ameliorated following weight loss in obese women. This finding demonstrates the beneficial effects of weight reduction on atherosclerosis risk.

Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides.

The aim of this study was to evaluate the relative contributions of various hormones involved in the regulation of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise and to assess the impact of obesity on this regulation. Eight lean and eight obese men performed a 60-min cycle exercise bout at 50% of their peak oxygen uptake on two occasions: during intravenous infusion of octreotide (a somatostatin analog) or physiological saline (control condition). Lipolysis in SCAT was evaluated using in situ microdialysis. One microdialysis probe was perfused with the adrenergic blockers phentolamine and propranolol while another probe was perfused with the phosphodiesterase and adenosine receptor inhibitor aminophylline. Compared with the control condition, infusion of octreotide reduced plasma insulin levels in lean (from approximately 3.5 to 0.5 microU/ml) and in obese (from approximately 9 to 2 microU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects. The octreotide-induced enhancement of exercise lipolysis in lean subjects was associated with an increased exercise-induced plasma NP response. Adenosine may contribute to the inhibition of basal lipolysis in both subject groups.

Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese women.

Type 2 diabetes and obesity are associated with an enhanced release of a number of adipocytokines. Hyperinsulinemia, frequently present in type 2 diabetes and obesity, might be one of the drivers of the enhanced production of adipocytokines. The aim of this study was to investigate the interstitial levels of cytokines in subcutaneous adipose tissue (SCAT) in response to hyperinsulinemia and the effect of weight-reducing hypocaloric diet on this regulation in obese subjects. Thirteen obese premenopausal women participated in the study. Concentrations of seven cytokines were measured in plasma and in AT interstitial fluid collected by microdialysis during a euglycemic-hyperinsulinemic clamp and during control infusion of physiological saline. A subgroup of six women underwent a 4-wk very-low-calorie diet (VLCD). Microdialysis during the clamp was performed before and at the end of VLCD. Hyperinsulinemia induced an increase of monocyte chemoatractant protein (MCP-1) and IL-6 SCAT interstitial and plasma levels and elevated IL-8 levels in SCAT. The relative changes of IL-6 levels in the dialysate correlated with changes of IL-8 and MCP-1. The interstitial and plasma levels of IL-1ß, IL-10, TNFα, and plasminogen activator inhibitor (PAI-1) remained unchanged in response to hyperinsulinemia. VLCD resulted in enhancement of the hyperinsulinemia-induced augmentation of MCP-1, IL-6, and IL-8 interstitial levels. In conclusion, hyperinsulinemia upregulates the interstitial levels of MCP-1, IL-6, and IL-8 in SCAT in obese women, whereas it does not affect IL-1ß, IL-10, TNFα, and PAI-1 levels. Hypocaloric diet associated with weight reduction enhances the hyperinsulinemia-induced upregulation of MCP-1, IL-6, and IL-8 in SCAT.

Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet.

OBJECTIVE: Adiponectin is a protein abundantly secreted by the adipose tissue (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we investigated the effect of weight reducing diet on the distribution of adiponectin isoforms in plasma and on their secretion in AT explants from obese subjects. DESIGN: A total of 20 obese subjects (age 37.8+/-7.3 years, body mass index 33.9+/-5.0 kg/m(2)) underwent eight weeks of very low-calorie diet (VLCD). A needle biopsy of subcutaneous abdominal AT and blood samples were taken before and after dietary intervention. AT explants were incubated in culture medium for 4 h. ELISA assay and western blot analyses were used to identify adiponectin complexes in culture media and in plasma. RESULTS: The distribution of adiponectin polymers in plasma was different from that secreted in human AT explants. Before VLCD, the relative amount of HMW isoform was 75.5+/-9.1% of total adiponectin in culture media and 52.2+/-11.2% in plasma. Despite the diet-induced weight loss and improvement of insulin sensitivity, VLCD neither induced change in total adiponectin level nor in the ratio of HMW to total adiponectin in plasma and in culture media of AT explants. CONCLUSIONS: The profile of adiponectin polymeric isoforms secreted by AT explants into culture media differs from the plasma profile. A dietary intervention leading to weight loss and improvement of insulin sensitivity was not associated with modifications of AT secretion of total or HMW adiponectin.

Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue.

The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity.

CONTEXT: Retinol-binding protein 4 (RBP4) may play a role in the development of insulin resistance. OBJECTIVE: We investigated whether RBP4 adipose tissue mRNA expression and plasma level are related to insulin sensitivity during a diet-induced weight loss. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Obese women followed a dietary intervention composed of a 4-wk very low-calorie diet (VLCD), a 2-month low-calorie diet, and 3-4 months of a weight maintenance (WM) phase. MAIN OUTCOME MEASURES: Clinical investigation was performed before and at the end of each phase. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp. Adipose tissue mRNA and plasma levels of RBP4 were determined using reverse transcription-quantitative PCR and ELISA, respectively. RESULTS: Weight and fat mass decreased during VLCD and were stabilized during WM. Glucose disposal rate increased during VLCD and remained elevated thereafter. Plasma levels of RBP4 decreased after VLCD and, although increasing at subsequent phases, remained lower than prediet values. Adipose tissue mRNA levels were diminished after VLCD, and increased during low-calorie diet and WM to reach basal values. Basal RBP4 levels or diet-induced variations of RBP4 were not different in lean women and two groups of obese women with high- and low-insulin sensitivity. CONCLUSIONS: Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. The study does not bring evidence for a role for RBP4 in the regulation of diet-induced changes in insulin sensitivity.