The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women

The aim of our study was to determine whether adipocyte-derived hormones leptin, adiponectin and resistin contribute to the improvement of insulin sensitivity after very-low calorie diet (VLCD). Therefore, serum levels of these hormones were measured in fourteen obese females before and after three weeks VLCD and in seventeen age- and sex-matched healthy controls. Body mass index, HOMA index, serum insulin and leptin levels in obese women before VLCD were significantly higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA 10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml, leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and soluble leptin receptors levels were significantly lower in obese women before VLCD than in the control group. No differences were found in serum glucose and resistin levels between the obese group before VLCD and the control group. VLCD significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels and increased soluble leptin receptor levels. The changes in serum adiponectin and resistin levels in obese women after VLCD did not reach statistical significance. We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not. Therefore, other mechanisms rather than changes in the endocrine function of the adipose tissue are probably involved in the VLCD-induced improvement of insulin sensitivity.     

Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans

Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-alpha). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-alpha on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% (P < 0.05) increase in plasma adiponectin and a 45% (P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% (P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-alpha (P < 0.01) and IL-6 plus its soluble receptor (P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.     

Transcriptomics applied to obesity and caloric restriction

Caloric restriction still remains the most efficient way to promote weight loss. Deciphering the molecular basis of adaptation to energy restriction is critical for the tailoring of new therapeutic strategies. This review focuses on the recent input of gene profiling on adipose tissue in obesity pathogenesis and on the new insights on adaptations occurring during very low caloric diet (VLCD) in humans. Hypocaloric diets improve a wide range of metabolic parameters including lipolytic efficiency, insulin sensitivity, and inflammatory profile. In the subcutaneous white adipose tissue (scWAT) the VLCD induced a decrease in the mRNA levels for the antilipolytic alpha2-adrenergic receptor associated with changes in catecholamine-induced adipocyte lipolytic capacity. The improvement in insulin sensitivity was not associated with a change in subcutaneous adipose tissue adiponectin gene expression or in its plasma level, suggesting that adiponectin is not involved in the regulation of VLCD-induced improvement of insulin sensitivity and that there is a small contribution of subcutaneous adipose tissue to plasma adiponectin levels. Pangenomic microarray studies in human scWAT revealed that a panel of inflammatory markers and acute phase reactants were over expressed in obese compared to lean subjects. Caloric restriction improved the inflammatory profile of obese subjects through a decrease of pro-inflammatory factors and an increase of anti-inflammatory molecules. These genes were mostly expressed in the stroma vascular fraction of the adipose tissue. Specific cell-type isolation and immunohistochemistry demonstrated that monocyte/macrophage lineage cells were responsible for the expression of both mRNA and protein inflammatory markers. The acute phase proteins serum amyloid A was highly expressed in mature adipocytes from obese subjects. Caloric restriction decreased both serum amyloid mRNA and circulating levels. Obesity now clearly appears as chronic low-grade inflammation state. Modulation of the inflammatory pathways may represent new therapeutic targets for the treatment of obesity-related complications.     

Effect of Zinc Supplementation on Inflammatory Markers and Adipokines in Young Obese Women

Obesity is a chronic inflammatory state characterized by altered adipokine production and increased levels of inflammatory cytokines. The study explored the effect of zinc supplementation on inflammatory markers and adipocyte hormones in young obese women. Twenty five non-obese women and forty obese women (body mass index ≥25 kg/m²) aged 19–28 years were recruited for this study. Twenty obese women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 obese women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Serum zinc and urinary zinc concentration were measured by Atomic Absorption Spectrophotometry. Inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 and adipocyte hormones such as lepin and adiponectin were measured by enzyme immunoassay. Inflammatory markers and leptin were significantly higher, but adiponectin was significantly lower in obese women than non-obese women. Zinc supplementation increased serum zinc by 15 % and urinary zinc by 56 % (P?<?0.05). The levels of hs-CRP (P?=?0.03) and IL-6 (P?=?0.006) significantly decreased with zinc supplementation, but not in placebo group. Serum leptin and plasma adiponectin concentration did not differ with either zinc supplementation or placebo. The levels of IL-6 and leptin were inversely associated with dietary zinc intake. These results suggest that zinc may have a favorable effect on obesity-related inflammation in young adults.     

Relationship between IL-6, leptin and adiponectin and variables of fibrinolysis in overweight and obese hypertensive patients.

Impaired fibrinolysis is a common finding in obese humans. This condition is now considered as an established risk factor for thromboembolic complications. Furthermore, obesity is characterized by a specific pattern of circulating concentrations of fat-cell products interleukin-6 (IL-6), leptin, and adiponectin. The aim of our study was to investigate the relationship between these proteins and selected variables of the fibrinolytic system in 74 mildly hypertensive, overweight subjects. Circulating IL-6 and leptin levels showed a positive association with BMI (r = 0.24, p = 0.04 and r = 0.70, p < 0.0001), whereas adiponectin was not correlated to BMI. Interestingly, IL-6 was also positively associated with t-PA/PAI-1 complexes after adjustment for BMI and other anthropometric variables. Leptin was positively correlated with PAI-1 activity and antigen (r = 0.32, p = 0.006 and r = 0.37, p < 0.001, respectively) and negatively with t-PA activity (r = -0.27, p = 0.03). However, these associations lost significance after correction for BMI or HOMA, an insulin sensitivity index. In contrast, adiponectin levels were independently and negatively correlated with PAI-1 antigen (r = -0.26, p = 0.04, after correction for BMI). In conclusion, our study provides further evidence that IL-6, leptin, and adiponectin are associated with impaired fibrinolysis in overweight hypertensive humans.     

L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice

We hypothesized that the apolipoprotein mimetic peptide L-4F, which induces arterial anti-oxidative enzymes and is vasoprotective in a rat model of diabetes, would ameliorate insulin resistance and diabetes in obese mice. L-4F (2 mg/kg/d) administered to ob/ob mice for 6 weeks limited weight gain without altering food intake, decreased visceral (P < 0.02) and subcutaneous (P < 0.045) fat content, decreased plasma IL-1beta and IL-6 levels (P < 0.05) and increased insulin sensitivity, resulting in decreased glucose (P < 0.001) and insulin (P < 0.036) levels. In addition, L-4F treatment increased aortic and bone marrow heme oxygenase (HO) activity and decreased aortic and bone marrow superoxide production (P < 0.001). L-4F treatment increased serum adiponectin levels (P < 0.037) and decreased adipogenesis in mouse bone marrow (P < 0.039) and in cultures of human bone marrow-derived mesenchymal stem cells (P < 0.022). This was manifested by reduced adiposity, improved insulin sensitivity, improved glucose tolerance, increased plasma adiponectin levels, and reduced IL-1beta and IL-6 levels in obese mice. This study highlights the existence of a temporal relationship between HO-1 and adiponectin that is positively affected by L-4F in the ob/ob mouse model of diabetes, resulting in the amelioration of the deleterious effects of diabetes.     

Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6

Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects (P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-α and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-α, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-α was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-α opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-α production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects.     

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases

Background

Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab.

Methodology/Principal Findings

11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a) levels significantly decreased.

Conclusions/Significance

Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels, which might reduce the cardiovascular risk of human subjects.     

Improvements in insulin resistance with weight loss, in contrast to rosiglitazone, are not associated with changes in plasma adiponectin or adiponectin multimeric complexes

It has been suggested that changes in adiponectin levels may contribute to improved insulin sensitivity in insulin-resistant individuals both after weight loss and after treatment with thiazolidinedione compounds. If this is correct, then changes in total circulating adiponectin and/or distribution of its multimeric complexes should coincide with improvements in insulin sensitivity after both interventions. To address this issue, fasting adiponectin concentrations and distribution of adiponectin complexes were measured in plasma samples in 24 insulin-resistant, nondiabetic subjects before and after 3-4 mo of treatment with either rosiglitazone or caloric restriction. The degree of insulin resistance in each group of 12 subjects was equal at baseline and improved to a similar extent ( approximately 30%) after each therapy. Whereas total adiponectin levels increased by nearly threefold and the relative amount of several higher molecular weight adiponectin complexes increased significantly in the rosiglitazone treatment group, there were no discernible changes in adiponectin levels or in the distribution between high or low molecular weight complexes in the weight loss group. These data indicate that, although changes in total adiponectin and several specific adiponectin complexes paralleled improvements in insulin resistance in thiazolidinedione-treated subjects, neither circulating adiponectin concentrations nor multimeric complexes changed in association with enhanced insulin sensitivity after moderate weight loss in 12 insulin-resistant, obese individuals.     

Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes

PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.     

The relationship between insulin sensitivity and serum adiponectin levels in three population groups.

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 +/- 0.99) and Asian-Indian subjects (HOMA = 3.41 +/- 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 +/- 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 +/- 4.39 microg/ml) compared to black (5.71 +/- 2.50 microg/ml) and Asian Indian (5.86 +/- 2.50 microg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.     

Circulating oxidized LDL and inflammation in extreme pediatric obesity

Oxidative stress and inflammation have not been well-characterized in extreme pediatric obesity. We compared levels of circulating oxidized low-density lipoprotein (oxLDL), C-reactive protein (CRP), and interleukin-6 (IL-6) in extremely obese (EO) children to normal weight (NW) and overweight/obese (OW/OB) children. OxLDL, CRP, IL-6, BMI, blood pressure, and fasting glucose, insulin, and lipids were obtained in 225 children and adolescents (age 13.5 ± 2.5 years; boys 55%). Participants were classified into three groups based on gender- and age-specific BMI percentile: NW (<85th, n = 127), OW/OB (85th- <1.2 times the 95th percentile, n = 64) and EO (≥1.2 times the 95th percentile or BMI ≥35 kg/m(2), n = 34). Measures were compared across groups using analysis of covariance, adjusted for gender, age, and race. Blood pressure, insulin, and lipids worsened across BMI groups (all P < 0.0001). OxLDL (NW: 40.8 ± 9.0 U/l, OW/OB: 45.7 ± 12.1 U/l, EO: 63.5 ± 13.8 U/l) and CRP (NW: 0.5 ± 1.0 mg/l, OW/OB: 1.4 ± 2.9 mg/l, EO: 5.6 ± 4.9 mg/l) increased significantly across BMI groups (all groups differed with P < 0.01). IL-6 was significantly higher in EO (2.0 ± 0.9 pg/ml) compared to OW/OB (1.3 ± 1.2 pg/ml, P < 0.001) and NW (1.1 ± 1.0 pg/ml, P < 0.0001) but was not different between NW and OW/OB. Extreme pediatric obesity, compared to milder forms of adiposity and NW, is associated with higher levels of oxidative stress and inflammation, suggesting that markers of early cardiovascular disease and type 2 diabetes mellitus are already present in this young population.     

The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance

BACKGROUND: The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. METHODS: We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. RESULTS: The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. CONCLUSIONS: These data indicate that circulating concentrations of TNF-alpha do not reflect the degree of insulin resistance in obesity and GHDA. They, however, do not exclude that TNF-alpha may induce insulin resistance at tissue level.     

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.     

Maternal and fetal leptin,adiponectin levels and associations with fetal insulin sensitivity

Objective:

It remains uncertain whether leptin and adiponectin levels are correlated in maternal vs. fetal circulations. Little is known about whether leptin and adiponectin affect insulin sensitivity during fetal life.

Design and Methods:

In a prospective singleton pregnancy cohort (n = 248), we investigated leptin and adiponectin concentrations in maternal (at 24‐28 and 32‐35 weeks of gestation) and fetal circulations, and their associations with fetal insulin sensitivity (glucose/insulin ratio, proinsulin level).

Results:

Comparing concentrations in cord vs. maternal blood, leptin levels were 50% lower, but adiponectin levels more than doubled. Adjusting for gestational age at blood sampling, consistent and similar positive correlations (correlation coefficients: 0.31‐0.34, all P < 0.0001) were observed in leptin or adiponectin levels in maternal (at 24‐28 or 32‐25 weeks of gestation) vs. fetal circulations. For each SD increase in maternal plasma concentration at 24‐28 weeks, cord plasma concentration increased by 12.7 (95% confidence interval 6.8‐18.5) ng/ml for leptin, and 2.9 (1.8‐4.0) µg/ml for adiponectin, respectively (adjusted P < 0.0001). Fetal insulin sensitivity was negatively associated with cord blood leptin (each SD increase was associated with a 5.4 (2.1‐8.7) mg/dl/µU/ml reduction in cord plasma glucose/insulin ratio, and a 5.6 (3.9, 7.4) pmol/l increase in proinsulin level, all adjusted P < 0.01) but not adiponectin (P > 0.4) levels). Similar associations were observed in nondiabetic full‐term pregnancies (n = 211).

Conclusions:

The results consistently suggest a maternal impact on fetal leptin and adiponectin levels, which may be an early life pathway in maternal‐fetal transmission of the propensity to obesity and insulin resistance.     

A short-term diet and exercise intervention ameliorates inflammation and markers of metabolic health in overweight/obese children

The present study was designed to examine the effects of short-term diet and exercise on markers of metabolic health, serum-stimulated production of inflammatory biomarkers from cultured monocytes and adipocytes, and serum lipomics. Twenty-one overweight/obese children (9 boys and 12 girls, age 13.0 ± 0.5 yr, BMI 33.0 ± 1.8 kg/m(2)) were placed on a 2-wk ad libitum, high-fiber, low-fat diet and daily exercise regimen. Fasting serum samples were taken pre- and postintervention for determination of cytokines, metabolic risk markers, and lipomics. Monocytes and adipocytes were incubated with pre- and postintervention serum to investigate changes in cytokine secretion. Correlative associations were calculated, followed by hierarchical clustering to determine relationships between fatty acid (FA) species and clinical biomarkers. Despite remaining overweight/obese, interleukin (IL)-6, IL-8, TNFα, PAI-1, resistin, amylin, leptin, insulin, and IL-1ra decreased and adiponectin increased. Culture studies indicated decreases in monocyte secretion of IL-6, TNFα, and IL-1β and adipocyte secretion of IL-6. Lipomic analysis revealed a decrease in total lipids and decreases in saturated FAs and an increase in 18:1/18:0. In general, Pearson's correlations revealed that inflammatory markers are negatively associated with a cluster of polyunsaturated FAs and positively correlated with several saturated FAs. These results indicate significant modification of multiple indices of metabolic health with short-term rigorous lifestyle modification in overweight/obese children prior to obesity reversal.     

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

IntroductionObesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD).Methods22 severe obese subjects (Median Body Mass Index (BMI): 44.5 kg/m²) were included in a dietary intervention study of 6 month, consisting of a very low calorie formula diet phase (VLCD: 800 kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR).ResultsMean body weight reduction by VLCD accounted to 21.7 kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (r_S = −0.642, p = 0.001) and HOMA (r_S = −0.419, p = 0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p = 0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p = 0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (r_S = −0.650, p = 0.022) during intervention.ConclusionAnti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.     

Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced M value (4.44 vs. 6.09 mg x kg(-1) x min(-1), P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls (P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 microg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11-13%) but significantly in both groups (P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin (P < 0.05) and positively correlated with insulin sensitivity (P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.     

Improved insulin sensitivity and adiponectin level after exercise training in obese Korean youth

Objective: The objective of this study was to investigate the association among adiposity, insulin resistance, and inflammatory markers [high‐sensitivity C‐reactive protein (hs‐CRP), interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α] and adiponectin and to study the effects of exercise training on adiposity, insulin resistance, and inflammatory markers among obese male Korean adolescents. Research Methods and Procedures: Twenty‐six obese and 14 lean age‐matched male adolescents were studied. We divided the obese subjects into two groups: obese exercise group (N = 14) and obese control group (N = 12). The obese exercise group underwent 6 weeks of jump rope exercise training (40 min/d, 5 d/wk). Adiposity, insulin resistance, lipid profile, hs‐CRP, IL‐6, TNF‐α, and adiponectin were measured before and after the completion of exercise training. Results: The current study demonstrated higher insulin resistance, total cholesterol, LDL‐C levels, triglyceride, and inflammatory markers and lower adiponectin and HDL‐C in obese Korean male adolescents. Six weeks of increased physical activity improved body composition, insulin sensitivity, and adiponectin levels in obese Korean male adolescents without changes in TNF‐α, IL‐6, and hs‐CRP. Discussion: Obese Korean male adolescents showed reduced adiponectin levels and increased inflammatory cytokines. Six weeks of jump rope exercise improved triglyceride and insulin sensitivity and increased adiponectin levels.