Fasting Plasma Leptin Concentrations Research Articles

Effects of using cassava as an amylopectin source in low protein diets on growth performance, nitrogen efficiency, and postprandial changes in plasma glucose and related hormones concentrations of growing pigs.

This study was aimed to explore the effect of using cassava as an amylopectin source in low protein (LP) diets on growth performance, nitrogen efficiency, and postprandial changes in plasma glucose and related hormones concentrations of growing pigs. Three animal experiments were included in the present study. Treatments included corn-soybean meal LP (Corn LP), corn-cassava-soybean meal LP (Corn + Cassava LP), and cassava-soybean meal LP (Cassava LP). The in vitro digestion proved that Corn + Cassava LP and Cassava LP diets induced more rapid starch digestion and glucose release, compared with Corn LP diet. The results of animal experiments are as follows: Cassava LP diet caused the most rapid changes in plasma glucose and relevant hormones concentrations after a meal. It decreased the concentrations of fasting plasma insulin, glucagon, and leptin concentrations compared with other treatments (P < 0.05). These modulations above led to a strong desire to eat and increased feed intake and then weight gain in growing pigs fed Cassava LP diet. Besides, feeding Cassava LP diet caused diarrhea, increased noxious gas release from feces, and increased concentrations of fecal isobutyrate and isovalerate (P < 0.05). Compared with Corn LP group, Corn + Cassava LP group showed significantly decreased urinary nitrogen (P < 0.05) and improved post-absorptive amino acid utilization efficiency. In conclusion, the use of cassava as an amylopectin source in LP diets could modulate glucose absorption and related gut secreted hormones secretion, subsequently strengthened the desire to eat, improved growth performance, and enhanced nitrogen efficiency in growing pigs.

Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates

Mouse studies linking adropin, a peptide hormone encoded by the energy homeostasis-associated (ENHO) gene, to biological clocks and to glucose and lipid metabolism suggest a potential therapeutic target for managing diseases of metabolism. However, adropin's roles in human metabolism are unclear. In silico expression profiling in a nonhuman primate diurnal transcriptome atlas (GSE98965) revealed a dynamic and diurnal pattern of ENHO expression. ENHO expression is abundant in brain, including ventromedial and lateral hypothalamic nuclei regulating appetite and autonomic function. Lower ENHO expression is present in liver, lung, kidney, ileum, and some endocrine glands. Hepatic ENHO expression associates with genes involved in glucose and lipid metabolism. Unsupervised hierarchical clustering identified 426 genes co-regulated with ENHO in liver, ileum, kidney medulla, and lung. Gene Ontology analysis of this cluster revealed enrichment for epigenetic silencing by histone H3K27 trimethylation and biological processes related to neural function. Dietary intervention experiments with 59 adult male rhesus macaques indicated low plasma adropin concentrations were positively correlated with fasting glucose, plasma leptin, and apolipoprotein C3 (APOC3) concentrations. During consumption of a high-sugar (fructose) diet, which induced 10% weight gain, animals with low adropin had larger increases of plasma leptin and more severe hyperglycemia. Declining adropin concentrations were correlated with increases of plasma APOC3 and triglycerides. In summary, peripheral ENHO expression associates with pathways related to epigenetic and neural functions, and carbohydrate and lipid metabolism, suggesting co-regulation in nonhuman primates. Low circulating adropin predicts increased weight gain and metabolic dysregulation during consumption of a high-sugar diet.

Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes: a randomised cross-over trial.

BackgroundWe have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study.MethodsIn a randomised, open-label, cross-over study, 13 patients with type 2 diabetes were randomly assigned to eat a Palaeolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, or a diabetes diet designed in accordance with current diabetes dietary guidelines during two consecutive 3-month periods. The patients were recruited from primary health-care units and included three women and 10 men [age (mean ± SD) 64 ± 6 years; BMI 30 ± 7 kg/m2; diabetes duration 8 ± 5 years; glycated haemoglobin 6.6 ± 0.6 % (57.3 ± 6 mmol/mol)] with unaltered diabetes treatment and stable body weight for 3 months prior to the start of the study. Outcome variables included fasting plasma concentrations of leptin, adiponectin, adipsin, visfatin, resistin, glucagon, insulin, C-peptide, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and ghrelin. Dietary intake was evaluated by use of 4-day weighed food records.ResultsSeven participants started with the Palaeolithic diet and six with the diabetes diet. The Palaeolithic diet resulted in a large effect size (Cohen’s d = −1.26) at lowering fasting plasma leptin levels compared to the diabetes diet [mean difference (95 % CI), −2.3 (−5.1 to 0.4) ng/ml, p = 0.023]. No statistically significant differences between the diets for the other variables, analysed in this study, were observed.ConclusionsOver a 3-month study period, a Palaeolithic diet resulted in reduced fasting plasma leptin levels, but did not change fasting levels of insulin, C-peptide, glucagon, incretins, ghrelin and adipokines compared to the currently recommended diabetes diet.Trial registration: ClinicalTrials.gov NCT00435240Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0398-1) contains supplementary material, which is available to authorized users.

Plasma leptin concentrations and esophageal hypomotility in obese patients.

Although esophageal hypomotility is prevalent in obese patients, its cause remains unknown. Leptin, a hormone derived from adipose tissue, may be involved in this phenomenon because it has been shown to decrease gastric and intestinal motility in animals. It has been hypothesized that elevated plasma leptin concentration is a risk factor for esophageal dysmotility in obese patients. To determine whether plasma leptin concentrations are higher in obese patients with esophageal hypomotility than in obese patients with a normal motility profile. Fasting plasma leptin concentration (assessed by radioimmuoassay) was measured in all patients who were included in a study protocol investigating esophageal manometry before bariatric surgery. The patients completed standardized surveys regarding epidemiological data, upper gastrointestinal symptoms, medical history and medication(s). Basal levels of leptin, as well as corrected leptin scores adjusted for sex and body mass index, were compared in patients with and without esophageal dysmotility. Nine patients without dysmotility and eight with dysmotility were included. Both groups were comparable with regard to age (42±9 versus 38±9 years), sex (78% versus 75% women) and body mass index (49±10 kg⁄m2 versus 42±7 kg⁄m2). There were no significant differences regarding medication(s) and comorbidities between the two groups. When compared with normal predicted values, the corrected leptin scores were 30% higher in patients with dysmotility than in the control group with normal motility (P≤0.05). Obese patients with esophageal dysmotility exhibited elevated plasma leptin concentrations, suggesting a role for leptin in promoting esophageal hypomotility.

Insulin action on GABA neurons is a critical regulator of energy balance but not fertility in mice.

Insulin signaling in the brain plays an important role in the central regulation of energy homeostasis and fertility, such that mice exhibiting brain-specific deletion of insulin receptors (InsRs) display a diet-sensitive obesogenic phenotype and hypothalamic hypogonadism. However, the specific neurons mediating insulin's central effects on fertility remain largely unidentified. The neurotransmitters γ-aminobutyric acid (GABA) and glutamate are important modulators of fertility and energy homeostasis and are widely distributed in the hypothalamus. We therefore investigated whether insulin signaling via GABAergic or glutamatergic neurons plays an important role in the metabolic regulation of fertility. We used the Cre-loxP system to generate mice with a selective inactivation of the Insr gene from GABAergic (Vgat(+)) or glutamatergic (Vglut2(+)) cells by crossing Insr-flox mice with Vgat-Cre or Vglut2-Cre mice, respectively. Multiple reproductive and metabolic parameters were then compared between male and female Insr-flox/Vgat-Cre(+) (VgatIRKO), Insr-flox/Vglut2-Cre(+) (VglutIRKO), and Insr-flox/Cre-negative control (CON) mice. Female VgatIRKO mice exhibited a significant increase in adult body weight, abdominal fat mass, and fasting plasma insulin and leptin concentrations, but normal fasting glucose concentration and glucose tolerance compared with CON mice. Surprisingly, VgatIRKO and VglutIRKO mice exhibited normal reproductive maturation and function compared with CONs. No differences in the age of puberty onset, estrous cyclicity, or fertility were observed between VgatIRKO, VglutIRKO, and CON mice. However, male VgatIRKO mice exhibited significantly augmented LH concentration and a trend toward reduced seminal vesicle weight compared with CON mice, which may be indicative of primary hypogonadism. Our results therefore demonstrate that insulin signaling via GABAergic and glutamatergic cells is not required for fertility in mice, but show that GABAergic neurons encompass circuitry through which insulin acts to modulate energy homeostasis.

Metabolic determinants of body weight after cats were fed a low-carbohydrate high-protein diet or a high-carbohydrate low-protein diet ad libitum for 8 wk

Overweight and obese conditions are common in cats and are associated with the development of a number of diseases. Knowledge of metabolic determinants and predictors of weight gain may enable better preventative strategies for obesity in cats. Lean, healthy cats were fed either a low-carbohydrate high-protein diet (n 16) or a high-carbohydrate low-protein (n 16) diet ad libitum for 8 wk. Potential determinants and predictors of final body weight assessed were body fat and lean masses, energy required for maintenance, energy requirements above maintenance for each kilogram of weight gain, insulin sensitivity index, fasting, mean 24-h and peak plasma glucose, insulin, and leptin concentrations, and fasting and mean 24-h serum adiponectin concentrations. In cats fed the low-carbohydrate high-protein diet, after adjusting for initial body weight, those with higher energy requirements for weight gain and higher fasting glucose concentration had higher final body weights (P ≤ 0.01). Predicted final body weights using initial body weight, fasting glucose and mean 24-h insulin concentrations (partial R2 37.3%) were imprecise. An equation using just initial body weight and fasting glucose concentration would be of more practical value, but was marginally less precise. In cats fed the high-carbohydrate low-protein diet, those with lower fasting leptin concentration initially had higher final body weights (P = 0.01). Predicted final body weights using initial body weight, energy requirements for maintenance, total body fat percentage and fasting leptin concentration (partial R2 39.2%) were reasonably precise. Further studies are warranted to confirm these findings and to improve the precision of predicted final body weights.

The Beneficial Effects of Early Short‐Term Exercise in the Offspring of Obese Mothers are Accompanied by Alterations in the Hypothalamic Gene Expression of Appetite Regulators and FTO (Fat Mass and Obesity Associated) Gene

Maternal overnutrition is implicated in the development of adult metabolic disease, and has been shown to alter the expression of genes involved in energy homeostasis. In the present study, we aimed to test whether a short period of voluntary exercise, followed by a sedentary period, would regulate hypothalamic markers involved in appetite. Adult female Sprague-Dawley rats were fed either normal chow or high-fat diet (HFD) ad lib. for 5 weeks, mated and continued on their assigned diet during gestation/lactation. At weaning males, were separated into chow or HFD groups; half were exercised (running wheels), whereas the remainder were sedentary. At week 10, wheels were removed and rats remained sedentary for 5 weeks, prior to tissue collection. Maternal obesity increased offspring adiposity at 15 weeks and this was exacerbated by postnatal HFD (P < 0.05). Body weight and fat mass were reduced in offspring of obese mothers if they exercised, and this was maintained even after 5 weeks without exercise. At 15 weeks, fasting plasma insulin, leptin and triglyceride concentrations were significantly reduced by exercise in offspring of lean and obese mothers consuming chow, with little benefit in those consuming HFD. Hypothalamic mRNA expression of pro-opiomelanocortin was increased by exercise but only in offspring of lean mothers. Exercise reduced hypothalamic FTO (fat mass and obesity associated) mRNA in offspring of lean dams regardless of diet. A short period of exercise early in life had lasting beneficial effects on body weight, adiposity and hormone profile of male offspring from obese and lean dams, despite being followed by a period of inactivity. The effects of exercise on hypothalamic appetite regulators were more marked in offspring of lean dams.

Investigation of the mechanisms contributing to the compensatory increase in insulin secretion during dexamethasone-induced insulin resistance in rhesus macaques

Dexamethasone has well-described effects to induce insulin resistance and increase insulin secretion. Herein, we examined potential contributors to the effect of dexamethasone to increase insulin secretion in rhesus macaques. Six male rhesus macaques received daily injections of either saline or dexamethasone (0.25 mg/kg i.m. for 7 days) in random order with 3 weeks between treatments. At the end of the treatment period, animals were fasted overnight and underwent a feeding study the next day, during which blood samples were taken before and for 60 min after a meal in order to assess islet hormone and incretin secretion. Dexamethasone induced marked increases in fasting plasma insulin, glucagon, leptin, and adiponectin concentrations (P<0.05). Surprisingly, the glycemic response after meal ingestion was decreased twofold during dexamethasone treatment (P<0.05). Dexamethasone-treated animals exhibited a significant increase in both insulin and glucose-dependent insulinotropic polypeptide (GIP) secretion during the feeding study (P<0.05). However, glucagon-like peptide-1 secretion was significantly lower in dexamethasone-treated animals compared with controls (P<0.01). Fasting and meal-stimulated pancreatic polypeptide concentrations (an index of the parasympathetic input to the islet) did not differ between saline and dexamethasone treatments. However, the proinsulin:insulin ratio was decreased throughout the feeding study with dexamethasone treatment suggesting an improvement of β-cell function (P<0.05). In conclusion, the maintenance of euglycemia and reduction of postprandial glycemia with short-term dexamethasone treatment appears to be due to the marked elevations of fasting and meal-stimulated insulin secretion. Furthermore, increases in postprandial GIP secretion with dexamethasone treatment appear to contribute to the effect of dexamethasone treatment to increase insulin secretion.

Clinical Impact of the Leptin to Soluble Leptin Receptor Ratio on Subclinical Carotid Atherosclerosis in Patients with Type 2 Diabetes

The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes. Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin. Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.

Site-specific circadian expression of leptin and its receptor in human adipose tissue

Circadian variability of circulating leptin levels has been well established over the last decade. However, the circadian behavior of leptin in human adipose tissue remains unknown. This also applies to the soluble leptin receptor. We investigated the ex vivo circadian behavior of leptin and its receptor expression in human adipose tissue (AT). Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI ≥ 40 kg/m²). Anthropometric variables and fasting plasma glucose, leptin, lipids and lipoprotein concentrations were determined. In order to investigate rhythmic expression pattern of leptin and its receptor, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h, using quantitative real-time PCR. Leptin expression showed an oscillatory pattern that was consistent with circadian rhythm in cultured AT. Similar patterns were noted for the leptin receptor. Leptin showed its achrophase (maximum expression) during the night, which might be associated to a lower degree of fat accumulation and higher mobilization. When comparing both fat depots, visceral AT anticipated its expression towards afternoon and evening hours. Interestingly, leptin plasma values were associated with decreased amplitude of LEP rhythm. This association was lost when adjusting for waist circumference. Circadian rhythmicity has been demonstrated in leptin and its receptor in human AT cultures in a site-specific manner. This new knowledge paves the way for a better understanding of the autocrine/paracrine role of leptin in human AT.

Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis

Data from studies in patients with nonalcoholic steatohepatitis (NASH) suggest an increased hepatic fatty acid oxidation. We have previously shown higher fasting plasma bile acid concentrations in patients with NASH. In-vivo and in-vitro studies suggest that bile acids by binding to peroxisome proliferator-activated receptor α activate fibroblast growth factor 21 (FGF21) and increase hepatic fatty acid oxidation. Plasma bile acid levels were quantified in healthy controls (n=38) and patients with biopsy-proven NASH (n=36). Plasma concentration of fatty acids, β-hydroxybutyrate, insulin, glucose, leptin, alanine aminotransferase, FGF21, and 8-hydroxydeoxyguanosine, a measure of oxidative stress, were measured in 16 healthy controls and 10 patients with NASH in the fasted state and in response to 3 h of infusion of intralipid. In a subgroup of these patients (n=6 each), plasma ceramide subspecies were quantified. Fasting plasma bile acids, FGF21, and leptin concentrations were significantly higher in patients with NASH. In response to intralipid infusion there was an increase in plasma β-hydroxybutyrate and free fatty acid levels in both controls and NASH; however, the ratio of β-hydroxybutyrate/free fatty acid was higher in NASH (P=0.02). Plasma FGF21 concentration increased in response to intralipid in patients with NASH only (P<0.01). Plasma leptin, insulin, glucose, and alanine transferase concentrations did not change in either group after infusion of intralipid. Increase in total ceramides in response to intralipid was greater in NASH. Elevated bile acids and FGF21 may be responsible for the higher hepatic fatty acid oxidation in NASH.

Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis

The hormonal mediators of obesity-induced insulin resistance and compensatory hyperinsulinemia in dogs have not been identified. Plasma samples were obtained after a 24-h fast from 104 client-owned lean, overweight, and obese dogs. Plasma glucose and insulin concentrations were used to calculate insulin sensitivity and β-cell function with the use of the homeostasis model assessment (HOMA insulin sensitivity and HOMA β-cell function, respectively). Path analysis with multivariable linear regression was used to identify whether fasting plasma leptin, adiponectin, or glucagon-like peptide-1 concentrations were associated with adiposity, insulin sensitivity, and basal insulin secretion. None of the dogs were hyperglycemic. In the final path model, adiposity was positively associated with leptin ( P < 0.01) and glucagon-like peptide-1 ( P = 0.04) concentrations. No significant total effect of adiposity on adiponectin in dogs ( P = 0.24) was observed. If there is a direct effect of leptin on adiponectin, then our results indicate that this is a positive relationship, which at least partly counters a negative direct relationship between adiposity and adiponectin. Fasting plasma leptin concentration was directly negatively associated with fasting insulin sensitivity ( P = 0.01) and positively associated with β-cell function ( P < 0.01), but no direct association was observed between adiponectin concentration and either insulin sensitivity or β-cell function ( P = 0.42 and 0.11, respectively). We conclude that dogs compensate effectively for obesity-induced insulin resistance. Fasting plasma leptin concentrations appear to be associated with obesity-associated changes in insulin sensitivity and compensatory hyperinsulinemia in naturally occurring obese dogs. Adiponectin does not appear to be involved in the pathophysiology of obesity-associated changes in insulin sensitivity.

Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats

EPA or fish oil supplementation has been suggested as treatments for the prevention of type 2 diabetes mellitus (T2DM) due to their lipid-lowering and potential insulin-sensitising effects. We investigated the effects of supplementation with EPA (1 g/kg body weight per d) or fish oil (3 g/kg body weight per d) on the age of onset of T2DM and circulating glucose, insulin, lipids, leptin and adiponectin in UC Davis (UCD)-T2DM rats. Animals were divided into three groups starting at 1 month of age: control, EPA and fish oil. All the animals were followed until diabetes onset or for up to 12 months of age. Monthly fasting blood samples were collected for the measurement of glucose, lipids, hormones and C-reactive protein (CRP). Neither EPA nor fish oil delayed the onset of T2DM or altered fasting plasma glucose, insulin, CRP, adiponectin or leptin concentrations. The groups did not differ in energy intake or body weight. Fish oil treatment lowered fasting plasma TAG concentrations by 39 (sd 7) % (P < 0.001) and EPA lowered fasting plasma NEFA concentrations by 23 (sd 5) % (P < 0.05) at 4 months of age compared with the control group. EPA and fish oil lowered fasting plasma cholesterol concentrations at 4 months of age by 19 (sd 4) and 22 (sd 4) % compared with the control group, respectively (both P < 0.01). In conclusion, EPA and fish oil supplementation lowers circulating lipid concentrations, but does not delay the onset of T2DM in UCD-T2DM rats.

The Legume Inflammation Feeding Experiment (LIFE): Effects of Gut Hormone Levels

The LIFE Study was designed to test the effects of a legume‐rich diet on biomarkers of insulin resistance (IR) and inflammation. A secondary objective was to test the effect of the diet on gut hormones: leptin, ghrelin (total), and cholecystokinin (CCK). Sixty‐four men (35‐75 yrs), who had undergone a screening colonoscopy within the past 2 years, were recruited in Central Pennsylvania to consume a legume diet (LG,1 1/2 cups of cooked dry beans) and an isocaloric average American diet (AA) in random order each for 4 weeks separated by a 3‐wk compliance break. Preliminary results show that fasting plasma leptin concentrations were reduced on both LG (‐0.118 ± 0.026 S.D. ng/mL, P&lt;0.0001) and AA diets (‐0.072 ± 0.019 ng/mL, P=0.0003) but the difference between diets was not statistically significant (P=0.1499). Fasting ghrelin levels slightly decreased on LG diet (‐15.289 ± 16.709 pg/mL) and increased on AA diet (19.129 ± 19.607 pg/mL); however, neither diet had an effect on ghrelin (P=0.3637 and P=0.3330, respectively). These results indicate that a legume‐rich diet may have favorable effects on lowering fasting leptin level with stable body weight. The measure and data analysis of CCK is ongoing. This study is supported by the National Cancer Institute and partial support provided by the GCRC, PSU.

Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies

IntroductionChronic low-grade inflammation is a significant factor in the development of obesity associated diabetes. This is supported by recent studies suggesting endotoxin, derived from gut flora, may be key to the development of inflammation by stimulating the secretion of an adverse cytokine profile from adipose tissue.AimsThe study investigated the relationship between endotoxin and various metabolic parameters of diabetic patients to determine if anti-diabetic therapies exerted a significant effect on endotoxin levels and adipocytokine profiles.MethodsFasting blood samples were collected from consenting Saudi Arabian patients (BMI: 30.2 ± (SD)5.6 kg/m2, n = 413), consisting of non-diabetics (ND: n = 67) and T2DM subjects (n = 346). The diabetics were divided into 5 subgroups based on their 1 year treatment regimes: diet-controlled (n = 36), metformin (n = 141), rosiglitazone (RSG: n = 22), a combined fixed dose of metformin/rosiglitazone (met/RSG n = 100) and insulin (n = 47). Lipid profiles, fasting plasma glucose, insulin, adiponectin, resistin, TNF-α, leptin, C-reactive protein (CRP) and endotoxin concentrations were determined.ResultsRegression analyses revealed significant correlations between endotoxin levels and triglycerides (R2 = 0.42; p < 0.0001); total cholesterol (R2 = 0.10; p < 0.001), glucose (R2 = 0.076; p < 0.001) and insulin (R2 = 0.032; p < 0.001) in T2DM subjects. Endotoxin showed a strong inverse correlation with HDL-cholesterol (R2 = 0.055; p < 0.001). Further, endotoxin levels were elevated in all of the treated diabetic subgroups compared with ND, with the RSG treated diabetics showing significantly lower endotoxin levels than all of the other treatment groups (ND: 4.2 ± 1.7 EU/ml, RSG: 5.6 ± 2.2 EU/ml). Both the met/RSG and RSG treated groups had significantly higher adiponectin levels than all the other groups, with the RSG group expressing the highest levels overall.ConclusionWe conclude that sub-clinical inflammation in T2DM may, in part, be mediated by circulating endotoxin. Furthermore, that whilst the endotoxin and adipocytokine profiles of diabetic patients treated with different therapies were comparable, the RSG group demonstrated significant differences in both adiponectin and endotoxin levels. We confirm an association between endotoxin and serum insulin and triglycerides and an inverse relationship with HDL. Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effect of RSG on insulin sensitivity.

Hydroxypropyl methylcellulose, a viscous indigestible polysaccharide, reduces adiposity and lowers plasma leptin and resistin concentrations in rats

Previous studies in this laboratory have suggested that viscous indigestible polysaccharides reduce adiposity with little or no effect on body weight. To further understand this effect, we have examined the effect of a viscous indigestible polysaccharide, hydroxypropyl methylcellulose (HPMC) on body composition and plasma adipokines in rats. Male Wistar rats were fed either a cellulose based control diet (no viscosity) (n = 12) or HPMC‐containing diet (high viscosity) (n = 24) for 6 weeks. Body composition was measured by dual X‐ray absorptiometry (DEXA) before and after 6 weeks of feeding. Rats fed the HPMC diet had a high intestinal contents viscosity whereas rat fed cellulose diet had no intestinal contents viscosity. After statistically adjusting for slight differences in final body weight, rats fed HPMC had significantly reduced body fat mass and greater lean body mass than the cellulose group, based on DEXA scanning and lower weights of epididymal and perirenal fat pads. Rats fed HPMC had significantly lower fasting plasma leptin and resistin concentrations. However, plasma adiponectin levels did not differ between the groups. There were no significant differences between groups in fasting plasma glucose or insulin levels. These results indicate that viscous indigestible polysaccharides reduce adiposity independent of an effect on body weight. (Supported by Imagenetix Inc.)

Errata

Leptin alters pancreatic exocrine and beta-cell secretion in animal studies. We hypothesized that leptin might be important in the pathogenesis of idiopathic chronic pancreatitis (ICP) and/or the development of diabetes in ICP. Fifty patients with ICP (25 with diabetes, 25 without diabetes) and 25 healthy controls were included in a prospective, case-control study. Fasting plasma leptin concentration was measured by enzyme-linked immunosorbent assay. Exocrine and endocrine pancreatic functions were assessed by fecal chymotrypsin and serum C-peptide, respectively. Anthropometric parameters and body fat mass (FM) were measured. Patients with ICP (mean age, 30 years; 33 men) had significantly lower body mass index (19.5 +/- 2.6 kg/m2) and FM (10.6 +/- 4.2 kg) as compared with controls (body mass index, 21.7 +/- 4.1 kg/m2; FM, 19.0 +/- 16.6 kg; P < 0.01). Fecal chymotrypsin (median, 5.2 [range, 0.3-42.6] U/kg) and C-peptide (median, 1.7 [range, 0.2-9.5] ng/mL) were significantly lower in patients than in controls (12.9 [range, 2.5-33.0] U/kg and 3.5 [range, 0.3-10.3] ng/mL; P < 0.01). Plasma leptin concentration was slightly lower but statistically insignificant in patients with ICP (median, 4.0 [range, 2.0-62.5] ng/mL) as compared with controls (median, 5.0 [range, 2.0-63.0] ng/mL). Patients with and those without diabetes were also comparable with regard to their leptin concentration, pancreatic functions, and anthropometric parameters. Leptin does not seem to have a pathophysiological role in either ICP or the development of diabetes in ICP.

Corrections

HomeHypertensionVol. 49, No. 2Corrections Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrections Originally published26 Dec 2006https://doi.org/10.1161/01.HYP.0000255633.14303.3aHypertension. 2007;49:e14This article corrects the followingAdiponectin Replenishment Ameliorates Obesity-Related HypertensionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 26, 2006: Previous Version 1 In a Hypertension article by K Ohashi et al (Ohashi K, Kihra S, Ouchi N, Kumada M, Fujita K, Hiuge A, Hibuse T, Ryo M, Nishizawa H, Maeda N, Shibata R, Walsh K, Funahashi T, Shimomura I. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006;47:1108–1116), there was a mistake in describing plasma adiponectin levels before adenovirus injection in Table 1. On day 11 post-injection of Ad-APN, plasma adiponectin concentrations were 56.8±5.0 μg/mL in KKAy/Ad-APN and 9.8±1.0 μg/mL in KKAy/Ad-β gal, as mentioned in the text. As a matter of course, the plasma adiponectin levels were significantly higher in KKAy/Ad-APN than in KKAy/Ad-β gal. Therefore, the correct Table 1 is shown here. The authors regret the error. TABLE 1. Characterization of Ad-β gal- and Ad-APN–Treated KKAy Mice. Plasma Concentrations of Adiponectin, Fasting Plasma Glucose (FPG), Insulin RI (IRI), HOMA-IR, Total Cholesterol (T-chol), Triglyceride (TG), Angiotensin II, Aldosterone, and Leptin Concentrations in Ad-β gal- and Ad-APN-Treated KKAy MiceVariablesAd-β gal (n=9)Ad-APN (n=9)PNS, not significant. Data are mean±SEM.Adiponectin, μg/mL9.8±1.056.8±5.0<0.01FPG, mmol/L10.35±0.8211.16±0.82NSIRI, μU/mL392.8±88.9352.3±38.8NSHOMA-IR183.0±20.1197.3±17.1NST-chol, mmol/L3.53±0.283.36±0.17NSTriglyceride, mmol/L1.55±0.161.67±0.15NSAngiotensin II, pg/mL172.7±83.5174.0±75.2NSAldosterone, pg/mL488.8±105.0412.7±147.1NSLeptin, ng/mL34.88±2.8131.08±2.76NS Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesAdiponectin Replenishment Ameliorates Obesity-Related HypertensionKoji Ohashi, et al. Hypertension. 2006;47:1108-1116 February 2007Vol 49, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/01.HYP.0000255633.14303.3a Originally publishedDecember 26, 2006 PDF download Advertisement

Insulin resistance, physical fitness, body composition and leptin concentration in 7–8 year-old children

The aim of this study was to investigate the association between insulin resistance and physical fitness, leptin concentration, body composition and family history for diabetes in non-selected young children. Physical fitness, fasting plasma glucose, insulin and leptin concentrations, anthropometric characteristics and medical history were available in two hundred and fifty-seven 7-year-old Dutch children. Correlations with the homeostasis model assessment (HOMA) index for insulin resistance were studied. A multiple regression model was calculated for HOMA. The differences between children with or without a family history for diabetes were not significant. Boys scored higher on glucose concentration and aerobic fitness and lower on sum of skin folds and leptin concentration (p<.05). After adjustment for sum of skin folds, HOMA was significantly associated with leptin in both genders (boys r=.184 p=.031; girls r=.430 p=.000). The association between physical fitness and HOMA was mediated by sum of skin folds. The associations were stronger in girls than in boys. In the regression model (R(2)=.205) the leptin concentration was the only significant predictor for HOMA. The influence of family history for diabetes on insulin resistance is shown as a trend at this age. Our findings suggest that plasma leptin concentration is independently associated with the development of insulin resistance in a non-selected prepubertal population. The association of physical fitness with insulin resistance seems to be mediated by the sum of skin folds.

Relationships between plasma leptin concentrations and human brain structure: A voxel-based morphometric study

We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioural processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32 ± 1 years, body fat 29 ± 1%, mean ± S.E.) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with GM volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen ( P < 0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness.