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Long-Term Effects of a Classic Ketogenic Diet on Ghrelin and Leptin Concentration: A 12-Month Prospective Study in a Cohort of Italian Children and Adults with GLUT1-Deficiency Syndrome and Drug Resistant Epilepsy.
De Amicis, R, Leone, A, Lessa, C, Foppiani, A, Ravella, S, Ravasenghi, S, Trentani, C, Ferraris, C, Veggiotti, P, De Giorgis, V, et al
Nutrients. 2019;(8)
Abstract
The classical ketogenic diet (cKD) is an isocaloric, high fat, very low-carbohydrate diet that induces ketosis, strongly influencing leptin and ghrelin regulation. However, not enough is known about the impact of a long-term cKD. This study evaluated the effects of a 12-month cKD on ghrelin and leptin concentrations in children, adolescents and adults affected by the GLUT1-Deficiency Syndrome or drug resistant epilepsy (DRE). We also investigated the relationship between the nutritional status, body composition and ghrelin and leptin variations. We carried out a longitudinal study on 30 patients: Twenty-five children and adolescents (15 females, 8 ± 4 years), and five adults (two females, 34 ± 16 years). After 12-monoths cKD, there were no significant changes in ghrelin and leptin, or in the nutritional status, body fat, glucose and lipid profiles. However, a slight height z-score reduction (from -0.603 ± 1.178 to -0.953 ± 1.354, p ≤ 0.001) and a drop in fasting insulin occurred. We found no correlations between ghrelin changes and nutritional status and body composition, whereas leptin changes correlated positively with variations in the weight z-score and body fat (ρ = 0.4534, p = 0.0341; ρ = 0.5901, p = 0.0135; respectively). These results suggest that a long-term cKD does not change ghrelin and leptin concentrations independently of age and neurological condition.
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The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies.
Larnkjær, A, Ong, KK, Carlsen, EM, Ejlerskov, KT, Mølgaard, C, Michaelsen, KF
Hormone research in paediatrics. 2018;(1):28-38
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Abstract
BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). METHODS Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. RESULTS At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. CONCLUSIONS Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin.
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Curcuminoids Lower Plasma Leptin Concentrations: A Meta-analysis.
Atkin, SL, Katsiki, N, Derosa, G, Maffioli, P, Sahebkar, A
Phytotherapy research : PTR. 2017;(12):1836-1841
Abstract
Curcumin is a naturally occurring polyphenol that has been suggested to improve several metabolic diseases. Leptin is an adipokine involved in metabolic status and appetite, with marked crosstalk with other systems. Available data suggest that curcumin may affect leptin levels; therefore, this meta-analysis was performed to evaluate this. A systematic review and meta-analysis were undertaken on all randomized controlled trials of curcumin studies that included the measurement of leptin. The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases. Quantitative data synthesis was performed by using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. A funnel plot, Begg's rank correlation, and Egger's weighted regression tests assessed the presence of publication bias. Four eligible articles comprising five treatment arms were selected for the meta-analysis. Meta-analysis showed a significant decrease in plasma leptin concentrations following curcumin treatment (standardized mean difference: -0.69, 95% confidence interval: -1.16, -0.23, p = 0.003; I2 = 76.53%). There was no evidence of publication bias. This meta-analysis showed that curcumin supplementation is associated with a decrease in leptin levels that may be regarded as a potential mechanism for the metabolic effects of curcumin. Copyright © 2017 John Wiley & Sons, Ltd.
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Benefits of resistance exercise in lean women with fibromyalgia: involvement of IGF-1 and leptin.
Bjersing, JL, Larsson, A, Palstam, A, Ernberg, M, Bileviciute-Ljungar, I, Löfgren, M, Gerdle, B, Kosek, E, Mannerkorpi, K
BMC musculoskeletal disorders. 2017;(1):106
Abstract
BACKGROUND Chronic pain and fatigue improves by exercise in fibromyalgia (FM) but underlying mechanisms are not known. Obesity is increased among FM patients and associates with higher levels of pain. Symptom improvement after aerobic exercise is affected by body mass index (BMI) in FM. Metabolic factors such as insulin-like growth factor 1 (IGF-1) and leptin may be involved. In this study, the aim was to evaluate the role of metabolic factors in lean, overweight and obese women during resistance exercise, in relation to symptom severity and muscle strength in women with FM. METHODS Forty-three women participated in supervised progressive resistance exercise, twice weekly for 15-weeks. Serum free and total IGF-1, IGF-binding protein 3 (IGFBP3), adiponectin, leptin and resistin were determined at baseline and after 15-weeks. Level of current pain was rated on a visual analogue scale (0-100 mm). Level of fatigue was rated by multidimensional fatigue inventory (MFI-20) subscale general fatigue (MFIGF). Knee extension force, elbow flexion force and handgrip force were assessed by dynamometers. RESULTS Free IGF-1 (p = 0.047), IGFBP3 (p = 0.025) and leptin (p = 0.008) were significantly decreased in lean women (n = 18), but not in the overweight (n = 17) and the obese (n = 8). Lean women with FM benefited from resistance exercise with improvements in current pain (p= 0.039, n = 18), general fatigue (MFIGF, p = 0.022, n = 18) and improved elbow-flexion force (p = 0.017, n = 18). In overweight and obese women with FM there was no significant improvement in pain or fatigue but an improvement in elbow flexion (p = 0.049; p = 0.012) after 15 weeks of resistance exercise. CONCLUSION The clearest clinical response to resistance exercise was found in lean patients with FM. In these individuals, individualized resistance exercise was followed by changes in IGF-1 and leptin, reduced pain, fatigue and improved muscular strength. In overweight and obese women FM markers of metabolic signaling and clinical symptoms were unchanged, but strength was improved in the upper limb. Resistance exercise combined with dietary interventions might benefit patients with FM and overweight. TRIAL REGISTRATION The trial was registered 21 of October 2010 with ClinicalTrials.gov identification number: NCT01226784 .
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Effects of Oral L-Carnitine Supplementation on Leptin and Adiponectin Levels and Body Weight of Hemodialysis Patients: a Randomized Clinical Trial.
Ahmadi, S, Dehghan Banadaki, S, Mozaffari-Khosravi, H
Iranian journal of kidney diseases. 2016;(3):144-50
Abstract
INTRODUCTION Carnitine supplementation may improve the general health and quality of life of hemodialysis patients by improving adipokines levels. The aim of the study was to investigate the effects of L-carnitine supplementation on leptin levels, adiponectin levels, and body weight of hemodialysis patients. MATERIALS AND METHODS Fifty hemodialysis patients were randomly divided into the carnitine group, who received oral L-carnitine, 1 g/L for 3 months, and the control group. Anthropometric measurements and serum levels of adipokines were measured at baseline and at the end of the intervention. RESULTS Forty-two participants completed the study. Serum leptin concentrations decreased after 12 weeks of the intervention in both groups, but these changes were not significant. The mean change of leptin concentration were, -1.7 ± 19.0 µg/mL and -7.1 ± 20.0 µg/mL in the carnitine group and the control group, respectively (P = .39). The mean adiponectin levels at baseline and after the intervention were 8.6 ± 11.19 µg/mL and 9.8 ± 4.1 µg/mL in the carnitine group (P = .67) and 5.0 ± 2.5 µg/mL and 11.2 ± 5.4 µg/mL in the control group, respectively (P < .001). Serum adiponectin levels increased significantly in the control group only. The decrease in body mass index was not significant. CONCLUSIONS This study showed that a daily supplementation of 1000 mg oral syrup of L-carnitine for 12 weeks did not affect leptin and adiponectin levels or the body weight or body mass index of hemodialysis patients.
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Nordic walking decreased circulating chemerin and leptin concentrations in middle-aged men with impaired glucose regulation.
Venojärvi, M, Wasenius, N, Manderoos, S, Heinonen, OJ, Hernelahti, M, Lindholm, H, Surakka, J, Lindström, J, Aunola, S, Atalay, M, et al
Annals of medicine. 2013;(2):162-70
Abstract
BACKGROUND Dysfunction of adipose tissue is one of the major factors leading to insulin resistance. Altered adipokine concentration is an early sign of adipose tissue dysfunction. The aim of this study was to assess the impact of exercise intervention on adipokine profile, glycemic control, and risk factors of the metabolic syndrome (MeS) in men with impaired glucose regulation (IGR). METHODS Overweight and obese men with IGR (n =144) aged 40-65 years were studied at baseline and at 12 weeks in a randomized controlled multicenter intervention study. BMI varied from 25.1 to 34.9. The subjects were randomized into one of three groups: 1) a control group (C; n =47), 2) a Nordic walking group (NW; n =48), or 3) a resistance training group (RT; n =49). RESULTS Leptin concentrations decreased in the NW group compared to both other groups. Both types of exercise intervention significantly decreased serum chemerin concentrations compared to the C group. In the NW group also body fat percentage, fatty liver index (FLI), and total and LDL cholesterol concentrations decreased compared to the RT group. CONCLUSIONS Nordic walking intervention seems to decrease chemerin and leptin levels, and subjects in this intervention group achieved the most beneficial effects on components of MeS.
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Effect of soybean protein on novel cardiovascular disease risk factors: a randomized controlled trial.
Rebholz, CM, Reynolds, K, Wofford, MR, Chen, J, Kelly, TN, Mei, H, Whelton, PK, He, J
European journal of clinical nutrition. 2013;(1):58-63
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BACKGROUND/OBJECTIVES Cardiovascular disease (CVD) is the leading cause of death in the United States and the world. Clinical trials have suggested that soybean protein lowers lipids and blood pressure. The effect of soybean protein on novel CVD risk factors has not been well studied. The objective of this study was to examine the effect of soybean protein on biomarkers of inflammation, endothelial dysfunction and adipocytokines. SUBJECTS/METHODS The effect of 8 weeks of 40 g of soybean protein supplement (89.3 mg isoflavones), 40 g of milk protein supplement and 40 g of complex carbohydrate placebo was examined in a randomized, placebo-controlled, double-blind, three-phase crossover trial among adults in New Orleans, Louisiana and Jackson, Mississippi. Plasma levels of inflammation biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-α), endothelial dysfunction biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, thrombomodulin) and adipocytokines (high-molecular weight adiponectin, leptin, resistin) were measured at baseline and at the end of each intervention using immunoturbidimetric and enzyme-linked immunosorbent assay techniques. RESULTS Soy protein supplementation resulted in a significant mean net change (95% confidence interval) in plasma E-selectin of -3.93 ng/ml (-7.05 to -0.81 ng/ml; P=0.014) compared with milk protein, and in plasma leptin of -2089.8 pg/ml (-3689.3 to -490.3 pg/ml; P=0.011) compared with carbohydrate. There were no significant changes in any other risk factors. CONCLUSIONS Soy protein supplementation may reduce levels of E-selectin and leptin. Further research is warranted to investigate the mechanisms through which protein may confer protective effects on novel CVD risk factors.
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Effects on metabolic variables after 12-month treatment with a new once-a-week sustained-release recombinant growth hormone (GH: LB03002) in patients with GH deficiency.
Roemmler, J, Gockel, A, Otto, B, Bidlingmaier, M, Schopohl, J
Clinical endocrinology. 2012;(1):88-95
Abstract
INTRODUCTION GH substitution in GH deficiency (GHD) must be subcutaneously administered daily. A new sustained-release formulation of GH (LB03002) has been developed, which has to be injected once a week. As a substudy to the phase III study, we performed this prospective study to evaluate the influence of LB03002 on metabolic variables and hormones. METHODS Eleven patients with GHD [four women/seven men, 58 years (29-69 years)] without GH therapy were included in the study. Eight patients were treated with LB03002 for 12 months and three patients received placebo for 6 months followed by LB03002 for 6 months. A 3-h oral glucose tolerance test (OGTT) was performed at study entry and at study end. Additionally, IGF-I, cholesterol, LDL, HDL, triglycerides, leptin, ghrelin, HbA1c and C-peptide were measured. Body composition was evaluated by dual-energy X-ray absorptiometry (DXA), and waist/hip ratio (WHR) and waist/height (WHtR) ratio were measured by tape and scale. RESULTS Multiple of upper limit of normal (xULN) of IGF-I (0·23 (0·09-0·4) vs 0·71 (0·4-1·04), P < 0·01), WHR (0·98 (0·86-1·04) vs 1·01 (0·86-1·05), P < 0·05) and ghrelin levels [119·8 ng/l (67·7-266·6) vs 137 ng/l (67-289·5), P < 0·05] were significantly higher, whereas fat mass (FM) [34·7% (20·4-49·2) vs 32·4% (16·7-48·5), P < 0·05] and leptin [11·2 μg/l (3·3-55·7) vs 7·05 μg/l (2·4-54·3), P < 0·05] were significantly lower at study end. Glucose, insulin, HOMA-IR, ISI, HOMA-β, C-peptide and HbA1c during OGTT were not significantly different before and after GH substitution, neither were BMI, WHtR, bone mineral density and lipid variables. CONCLUSION Substitution with LB03002 showed statistically significant reduction in FM, which reduces leptin levels and increases ghrelin levels but does not seem to influence glucose and lipid metabolism.
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Adiponectin-leptin ratio: a useful estimate of insulin resistance in patients with Type 2 diabetes.
Zaletel, J, Barlovic, DP, Prezelj, J
Journal of endocrinological investigation. 2010;(8):514-8
Abstract
AIMS: Adiponectin and leptin are adipocytokines associated with insulin resistance. The objective of this study was to evaluate the performance of the adiponectin-leptin ratio as a measure of insulin resistance in comparison with other surrogate measures of insulin resistance based on fasting insulin and glucose levels [homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), fasting glucose/insulin ratio] and with measures based on fasting insulin and triglyceride levels (McAuley index) in Caucasian patients with Type 2 diabetes (T2D). METHODS In 70 patients included in DEMAND (delapril and manidipine for nephroprotection in diabetes) study, fasting samples of plasma insulin and adiponectin were determined by a radioimmunoassay, whereas plasma leptin was determined by an enzyme-linked immunosorbent assay. Insulin resistance estimates were derived by the established equations and compared with the direct measurement of insulin resistance obtained with the euglycemic hyperinsulinemic clamp. Insulin resistance estimates and the clamp derived sensitivity index were compared by correlation analysis. RESULTS The adiponectin-leptin ratio correlated best with the clamp derived sensitivity index (r=0.553, p<0.001) compared to other surrogate measures of insulin resistance. In multiple linear regression models including different surrogate measures of insulin resistance as independent predictors of the sensitivity index, the model with the adiponectin-leptin ratio accounted for the highest variability of the sensitivity index (r2=0.336, p<0.001). CONCLUSIONS The adiponectin-leptin ratio is associated with insulin resistance, measured with the euglycemic hyperinsulinemic clamp, in Caucasians with T2D. The association with clamp derived sensitivity index is even stronger than that of HOMA, QUICKI, fasting glucose/insulin ratio or McAuley index and is independent of body mass index or glycemic control. The adiponectin-leptin ratio promises to become a new laboratory marker of insulin resistance in T2D.
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Effects on serum lipid and leptin levels of three different doses of norethisterone continuously combined with a fixed dose of 17beta-estradiol for nasal administration in postmenopausal women: a controlled, double-blind study.
Castelo-Branco, C, Palacios, S, Vázquez, F, Villero, J, Ferrer, J, Ascaso, C, Balasch, J
Fertility and sterility. 2007;(2):383-9
Abstract
OBJECTIVE To evaluate the effect of intranasal continuous combined hormone therapy on serum lipids and leptin levels in healthy postmenopausal women. DESIGN Multicenter, double-blind, double-dummy, randomized, controlled study conducted in parallel groups. SETTING Outpatient clinics of three Spanish hospitals and two private health centers. PATIENT(S): A total of 333 healthy postmenopausal women aged 40 to 75 years. INTERVENTION(S): Women were randomly allocated to either one of three different doses of norethisterone (50 microg/day, 175 microg/day, or 550 microg/day) continuously combined with a fixed dose of 17beta-estradiol (350 microg/day) for nasal administration, or 17beta-estradiol at 2 mg/day combined with oral norethisterone acetate at 1 mg/day. MAIN OUTCOME MEASURE(S): Serum lipid, glucose, and leptin levels were assessed at baseline and after 12, 24, 36, and 52 weeks of treatment. RESULT(S): Overweight women (body mass index >25 kg/m(2)) had higher baseline leptin levels, but these levels increased in all groups across the study unrelated to body mass index. Both intranasal and oral therapy had the effect of increasing the levels of leptin after 24 weeks in healthy postmenopausal women. As expected, total cholesterol and low-density lipoprotein cholesterol levels decreased and high-density lipoprotein levels increased in the four groups. CONCLUSION(S): Body mass index is a strong determinant of serum leptin levels in healthy postmenopausal women; serum leptin increased in all the hormone therapy regimes.