Fasting Leptin Research Articles

FRI005 Appetite Response To Short-term Energy Restriction In Young Healthy Women

Abstract Disclosure: G.E. Choi: None. C. Okigbo: None. J. Tessa Tonleu: None. S. Shekhar: None. H.F. Leka: None. A.E. Kim: None. B. Purse: None. K.R. Hisch: None. A.E. Smith-Ryan: None. J.E. Hall: None. Short-term caloric restriction, also referred to as energy restriction (ER), is commonly used by women across the weight spectrum to address their weight or health. Chronic ER is associated with increased appetite, but the relationship is poorly characterized in short-term ER or in the absence of obesity. We investigated the impact of controlled short-term ER on appetite and relevant hormone mediators in young women. In the early follicular phase of two menstrual cycles, 19 healthy non-obese women aged 23.36 ± 2.08 years (mean ± SD) with a BMI of 23.15 ± 2.34 kg/m2 (mean ± sem) underwent two five-day diet and exercise interventions: neutral energy availability (NEA) = 45 kcal/kg lean body mass (LBM)/day and deficient energy availability (DEA) = 20 kcal/kg LBM/day. On day 5 of both interventions, a visual analog scale (VAS) appetite questionnaire, body weight, fasting leptin and orexin-A were measured. We used paired t-tests for comparisons of changes from NEA to DEA. Principal-component factor analysis divided VAS items into appetite, satiety, and hunger (Cronbach alphas >0.80). We utilized linear regression models to determine how changes (Δ) in body weight, leptin, and orexin-A affect appetite, satiety, hunger, and cravings. From NEA to DEA, appetite and hunger increased (55% vs 76%; p<0.001 and 52% vs 71%; p<0.001, respectively), while satiety and cravings decreased (42% vs 19%; p <0.01 and 49% to 38%; p<0.01, respectively). DEA resulted in a weight loss of 1.0±0.22 kg (p<0.001), a decrease in leptin of 3.13±0.95 ng/ml, p=0.002), and increased orexin-A (0.06±0.02 ng/ml, p=0.018). Δ body weight was positively associated with Δ leptin (p=0.001) but not Δ orexin-A. When adjusting for leptin and orexin-A, increased appetite was associated with weight loss (p=0.011). Δ satiety was independently correlated with Δ body weight (p=0.002) and Δ leptin (p=0.033). Δ hunger was positively correlated with Δ body weight (p=0.043), independent of Δ orexin-A). Δ leptin, orexin-A, or body weight did not correlate with Δ craving. Thus, even in non-obese women, short-term ER results in a profound effect on homeostatic mechanisms designed to maintain weight; increased appetite and decreased satiety are mediated by even a minor degree of weight loss, both independently and through decreased leptin. It is likely that changes in ghrelin also contribute to these adaptations to ER, however it was not measured in this study for technical reasons. Interestingly, the effect of short-term ER on specific food cravings is overwhelmed by the overall increase in appetite. Presentation: Friday, June 16, 2023

FRI006 Appetite And Food Intake-regulating Hormones In Patients With Craniopharyngioma

Abstract Disclosure: C.S. Martins: None. M.C. Nogueira: None. A. Bueno: None. A.S. Berbel-Júnior: None. A.C. Moreira: None. S.R. Antonini: None. M. De Castro: None. Purpose: In patients with adamantinomatous craniopharyngiomas (aCP), hypothalamic obesity may occur due to hypothalamic involvement by the tumor or therapeutic interventions. Studies on appetite sensations and modulation of orexigenic and anorexigenic hormones may contribute to understand the pathogenesis of obesity in aCP patients. Patients and Methods: Fifteen patients (9F, 6M; 31.1±12.0 years) presenting aCP submitted to surgical resection and 15 controls paired by sex, age (31±11.7 years) and Body Mass Index (BMI) were evaluated. Leptin and adiponectin were measured in basal conditions, whereas glucose, insulin, GLP-1, PYY and ghrelin levels were assessed in basal conditions and 30, 60, 120 and 180 minutes after a standard meal test consisted by 70 g of hyposodic soy protein isolate-based powder diluted in 250 mL water to be consumed in up to 10 minutes, resulting in a drink of 315 Kcal with 44.1 g carbohydrate, 10.5 g fat, and 11.0 g protein (56%, 30%, and 14% of total calories, respectively). At the same time points, sensations of hunger, fullness and prospective food consumption were measured by a Visual Analogic Scale (VAS) composed of horizontal lines. Individuals were asked to mark across the line the point correspondent to their sensations, and the distance to the left end of the line was quantified. The term “hunger” was evaluated by the question “How much hunger do you feel?” The answers at the VAS were “I’m not hungry at all” and “I’ve never been so hungry.” The feeling of fullness was evaluated by the question “How satisfied are you?” and the answers were “I am completely empty” and “I am completely full.” Prospective consumption was evaluated by the question “How much do you think you can eat?” and the answers were “nothing” and “too much”. Results: Patients’ BMI were 30.9 ± 7.6 kg/m2. In aCP patients, differently from controls, the decrease of hunger from baseline to 60 minutes after the meal was not observed, demonstrating a more transient reduction in the sensation of hunger. In addition, a decrease of fullness sensation from 30 to 120 minutes (p=0.03) was observed, demonstrating a less durable sensation of fullness. There was a tendency towards higher fasting leptin concentrations in patients with aCP (p=0.06), while adiponectin levels were lower in patients (p=0.002). Insulin (p=0.01) and HOMA-IR (p=0.001) were higher in aCP patients compared to controls at 3 hours after meal, whereas GLP-1 (P=0.03) and PYY (p=0.02) were higher at 2 hours after the meal. PYY and ghrelin showed earlier postprandial rise and fall, respectively, in aCP patients. Conclusions: After the test, aCP patients exhibited more transient reduction in the sensation of hunger and less durable sensation of fullness than controls. Changes in appetite sensations and unregulated secretion of orexigenic and anorexigenic hormones may contribute to increased food intake and to the pathogenesis of obesity in aCP patients. Presentation: Friday, June 16, 2023

Metabolic surgery-induced changes of the growth hormone system relate to improved adipose tissue function

AimsBody weight loss improves insulin resistance and growth hormone secretion in obesity, which may be regulated by leptin according to preclinical studies. How changes in leptin, lipids and insulin sensitivity after bariatric (metabolic) surgery affect the human growth hormone system is yet unclear.Participants and methodsPeople with obesity (OBE, n = 79, BMI 50.8 ± 6.3 kg/m2) were studied before, 2, 12, 24 and 52 weeks after metabolic surgery and compared to lean healthy humans (control; CON, n = 24, BMI 24.3 ± 3.1 kg/m2). Tissue-specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps with D-[6,6-2H2]glucose. Fasting leptin, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and IGF-binding proteins (IGFBP1, IGFBP3) were measured using ELISA.ResultsAt baseline, OBE exhibited higher glycemia and leptinemia as well as pronounced peripheral, adipose tissue and hepatic insulin resistance compared to CON. GH and IGFBP1 were lower, while IGF1 was comparable between groups. At 52 weeks, OBE had lost 33% body weight and doubled their peripheral insulin sensitivity, which was paralleled by continuous increases in GH, IGF-1 and IGFBP1 as well as decrease in leptin. The rise in GH correlated with reductions in free fatty acids, adipose tissue insulin resistance and insulinemia, but not with changes in body weight, peripheral insulin sensitivity, glycemia or leptinemia. The rise in IGF-1 correlated with reduction in high-sensitive C-reactive protein.ConclusionReversal of alterations of the GH-IGF-1 axis after surgically-induced weight loss is unlikely related to improved leptin secretion and/or insulin sensitivity, but is rather associated with restored adipose tissue function and reduced low-grade inflammation.

PMON307 Adipokines and Bone Health in Hispanic Children

Abstract Introduction Leptin and adiponectin are adipocytokines with important metabolic functions. Leptin to adiponectin ratio is a marker of adipose tissue dysfunction and is associated with insulin resistance and cardiometabolic risk. We previously reported a negative effect of adiposity on bone health. We examined the relationship of adipokines to bone mass in a large cohort of Hispanic youth. We hypothesized that adipocytokine dysregulation in childhood may contribute to adverse bone health in children with obesity. Methods We studied 501 (237 males and 264 females) children and adolescents from the Viva la Familia Study. They were all pubertal; mean age (SD) 14.1 (2.5) years; 27% were normal weight (NW), 20% overweight (OW) and 53% obese (OB). They underwent measurement of body composition, total body less head bone mineral content (BMC) and density (BMD) by DXA scan; fasting leptin and adiponectin. The leptin to adiponectin ratio was calculated. Results Leptin concentration and leptin to adiponectin ratio were higher in OW and OB compared to NW (p<.001) whereas adiponectin was lower in OW and OB compared to NW (p<.001). After adjusting for sex, age, Tanner stage and lean mass, BMC was inversely related to leptin (r = -0.15, p =.001) and leptin to adiponectin ratio (r = -0.20, p <.001) but positively related to adiponectin (r = 0.12, p =.007). Similar relationships were found for BMD. In a regression model with BMC as the dependent variable, together and independently of sex, age, Tanner stage, lean mass and fat mass, leptin to adiponectin ratio negatively contributed (β = -0.060, p=.002) to the variance of BMC (R2 = 0.877, p <.001). Similar findings were seen with BMD as the dependent variable. Conclusion Elevated leptin to adiponectin ratio, a manifestation of adipokine dysregulation, may contribute negatively to bone health (BMC and BMD) in children with overweight/obesity. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

OR10-2 Hormonal and Cardiometabolic Changes Associated with Diazoxide Choline Extended-Release (DCCR) Tablets in Patients with Prader-Willi Syndrome

Abstract Background Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental condition, characterized by hyperphagia, obesity, hormone deficiencies and behavioral/psychological manifestations. DCCR is under investigation as a treatment for hyperphagia in PWS through its actions on hypothalamic circuits involved in appetite regulation including NPY neurons and central inhibition of DMV neurons to improve insulin sensitivity. In addition to these effects, DCCR acts on pancreatic beta cells, to reduce glucose stimulated insulin secretion, which might have additional effects to reduce fat deposition in adipocytes, serum leptin concentrations and insulin resistance. Objectives and methods This analysis characterized changes in hormonal and cardiometabolic parameters in patients with PWS receiving oral daily DCCR. 125 participants with genetically-confirmed PWS ≥4 years old with hyperphagia were treated with DCCR in multi-center studies conducted at 29 sites in the US and the UK: a 13-week, Phase 3, double-blind, placebo-controlled study (DESTINY PWS) and its long-term, open-label extension study (analysis at 52 weeks). The target DCCR dose for these studies was ≥3.3 mg/kg with an optimal dose of 4.2 - 5.8 mg/kg. Overall, 103 patients received DCCR (100-525 mg/day) for 52 weeks. For all parameters, the baseline measurement was defined as (immediately prior to) start of DCCR treatment. Results Serum leptin, insulin, and HOMA-IR were significantly reduced following 52 weeks of DCCR administration. Results are expressed as Least square (LS) mean change from baseline [Standard Error (SE)]. There were significant decreases in: Leptin (ng/mL) = -11.08[1.26], p<0.001; Insulin (μIU/mL) = -2.5[0.69], p<0.001; and HOMA-IR = -0.5 [0.17], p=0.003. Serum adiponectin (µg/mL) was significantly increased: 1.82[0.41], p < 0.001. Fat mass measured by DXA was stable at 52 weeks. Conclusions The reductions in fasting leptin, insulin and HOMA-IR, and the increase in adiponectin with prolonged DCCR treatment in the absence of reductions in total body fat are consistent with improved insulin sensitivity that may also reflect improvement in leptin sensitivity and healthier body fat distribution, such as reduced visceral adiposity. This could result from both direct pancreatic and hypothalamus-to-periphery actions of DCCR. It remains to be determined if such beneficial metabolic changes also result in reduced systemic inflammation and cardiovascular health. DCCR administration was associated with significant reductions in leptin, insulin, and HOMA-IR, increases in adiponectin and stabilization of body fat. These and other changes in cardiometabolic parameters suggest that DCCR may have long term health benefit in patients with PWS. Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.

RF23 | PSAT266 The Relationship Between Thyroid Function and Body Mass Index, Leptin, Adiponectin, and Insulin Resistance in Euthyroid Subjects Before and After Laproscopic Sleeve Gastrectomy

Abstract The relationship between obesity and thyroid function tests (TFT) has been studied in the past decades with increasing interest, however, studies have been inconsistent . The objectives of this study were to examine the effect of weight loss induced by laparoscopic sleeve gastrectomy(LSG) on TFT in obese euthyroid subjects and to correlate that with the changes in serum leptin, adiponectin, and insulin resistance.55 euthyroid obese subjects(BMI > 30) and 52 non-obese (BMI < 30), age-matched controls were recruited at baseline. We measured body weight, BMI, body composition, thyroid-stimulating hormone (TSH), Free T4 (FT4), Free T3(FT3), fasting leptin, adiponectin. Insulin resistance was quantified by HOMA-IR. Data are presented as mean ± SEM. The same parameters were repeated at 3- and 6-months in the obese group. Obese subjects had significantly higher TSH compared to non-obese subjects, 2.7 ±0.18 V.s 1.7±0.13 (normal range 0.27-4.2 mIU/L . Mean FT3 was 3.9± 0.1pmol/L (normal 3.1-6.8) in obese subjects compared to 5.0 ± 0.1 pmol/L in the non-obese controls, respectively, P value 0.001, however, FT4 (Normal 12-22 pmol/L) was similar in the two groups.Repeated measures ANOVA showed significant reduction in body weight from 140±26.5 kg at baseline to 115.8 ± 22.3 kg at 3 months, P < 001, and 104.2 ± 21.1 kg at 6 months, P<0.001, respectively. Serum TSH (N=48) reduced from 2.6 ±0.86 at baseline, to 2.0 ± 0.85 at 3 months, P = 0.06, and was 2.2± 0.78, at 6 months, P=0.23, in comparison with baseline, N=47). Free T3 reduced from 3.7.0 ± 0.41 pmol/L at baseline to 3.2 ±0.4 at 3 months (P < 0.9) and increased to 3.9± 0.53 at 6 months, P < 0.33. Changes in FT4 were not significant at 3 and 6 months, respectively. HOMA-IR reduced within 6 months and correlated with baseline FT3 .Serum leptin (N=38) significantly reduced from 25.9 ng/ml at baseline to 17.5 ng/ml at 3 months(p=0.037) to 15.2 ng/ml at 6 months, respectively, P < 0.011 compared to baseline. On the other hand, serum adiponectin (N=22) significantly increased from the baseline value of 9.2 ng/ml to 12.4 ng/ml at 3 months (p=0.001) and 16.6 ng/ml at 6 months(p<0.001 from baseline). TSH and Free T3 tend to decrease within 6 months following weight loss with LSG in obese subjects . Serum leptin significantly decreased and serum adiponectin significantly increased following LSG, however, there were no correlations between the changes in these adipose tissue markers and TFTs . We speculate that the changes in TSH and FT3 in obese euthyroid subjects may be due to the influence of the obesity and are unlikely to be causative, since they tend to reverse after weight loss, however, further studies on larger numbers of patients are needed to further explore the relationship between obesity and TFTs. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:48 p.m. - 12:53 p.m.

Influence of Training and Single Exercise on Leptin Level and Metabolism in Obese Overweight and Normal-Weight Women of Different Age.

Leptin is one of the important hormones secreted by adipose tissue. It participates in the regulation of energy processes in the body through central and peripheral mechanisms. The aim of this study was to analyse the anthropological and physical performance changes during 9 month training in women of different age and body mass. The additional aim was the analysis of leptin levels in the fasting stage and after a control exercise. Obese (O), overweight (OW), and normal-weight (N) women participated in the study. Additional subgroups of premenopausal (PRE) (<50 years) and postmenopausal (POST) (50+) women were created for leptin level analysis. The main criterion of the division into subgroups was the age of menopause in the population. The control submaximal test and maximal oxygen uptake (VO2max) according to Astrand–Rhyming procedures was performed at baseline and after 3, 6, and 9 months. Before each control test, body weight (BM), body mass index (BMI), percentage of adipose tissue (% FAT), and mass (FAT (kg)) were measured. Moreover, before and after each test, leptin level was measured. After 9 months, there was a significant decrease in BM in the O (p < 0.05) and OW (p < 0.05) groups with no significant changes in the N group. There was a decrease in BMI in both the O (p < 0.05) and the OW (p < 0.05) groups, with no changes in the N group. The % FAT reduction was noted only in the O group (p < 0.05). VO2max increased in each of the measured groups (p < 0.05). The fasting leptin level at 0, 3, 6, and 9 months were the highest in the O group. The fasting leptin level before training was highest in the O group compared to the OW group (p < 0.01) and the N group (p < 0.01). It was also higher in the OW group compared to the N group at baseline (0) (p < 0.01) and after 3 and 6 months (p < 0.01). After 9 months, the leptin concentration decreased by 20.2% in the O group, 40.7% in the OW group, and 33% in the N group. Moreover, the fasting leptin level was higher in the POST subgroup compared to the PRE group in the whole group of women (p < 0.05). After a single exercise, the level of leptin in the whole study group decreased (p < 0.05). This was clearly seen, especially in the POST group. The 9 month training had a reducing effect on the blood leptin concentration in groups O, OW, and N. This may have been a result of weight loss and the percentage of fat in the body, as well as systematically disturbed energy homeostasis.

Serum leptin and neuropeptide Y in patients with cystic fibrosis-A single center study.

Along with the significant elongation in the average life expectancy of patients with cystic fibrosis (CF), there are still significant discrepancies in the height, weight, and body mass index (BMI) of patients compared to controls without CF. The correlation between hormones that regulate appetite and body fat mass may be an additional factor in weight loss or poor weight gain in CF patients. Our objective was to estimate serum concentrations of leptin and neuropeptide Y in patients with CF as well as to assess correlations between studied hormones and the clinical parameters of CF. Leptin and neuropeptide Y serum concentrations after an overnight fast were measured using an enzyme-linked immunosorbent assay. All study participants had anthropometric tests and spirometry. In addition, fasting serum lipid profile was also analyzed. Fasting leptin levels in CF were significantly higher in patients with CF patients (13.9 ± 6.9 vs. 6.5 ± 2.6 ng/mL, p < 0.001) compared to controls. There were no differences in leptin concentration between female and male CF participants (15.7 ± 7.8 vs. 12.2 ± 5.6 ng/mL, p = 0.13). Leptin was correlated with age (R = 0.64, p < 0.001), BMI (R = 0.65, p < 0.001), spirometry results (R = −0.49, p < 0.01), and body fat (R = 0.5, p < 0.05). There were no differences in neuropeptide Y concentration between participants with CF and controls as well as neuropeptide Y was not correlated with any studied parameters. The results of our study suggest that weight loss may be associated with a decreased level of leptin, while reduced pulmonary function in CF may be related to an elevated level of leptin.

Obesity and overweight phenotypes in patients with systemic lupus erythematosus based on body mass index and serum leptin levels: a pilot cross-sectional study

Objective – to identify obesity/overweight phenotypes in patients with systemic lupus erythematosus (SLE) based on the body mass index (BMI) and serum leptin levels assessment, and to clarify the relationship of these phenotypes with different metabolic disorders.Material and methods. The study included 51 patients with SLE (48 women, 3 men) without diabetes mellitus. The median age of patients was 40 [31; 48] years, disease duration was 3.0 [0.6; 9.0] years. Glucocorticoids were received by 84% of patients, hydroxychloroquine – by 76%, immunosuppressants – by 20%, biological agents – by 10%. BMI was calculated and the fasting leptin level in serum was determined (ELISA) in all patients. Leptin concentrations &gt;11.1 ng/ml in women and &gt;5.6 ng/ml in men corresponded to hyperleptinaemia. There were three main obesity/overweight phenotypes: “classic” (BMI≥25 kg/m2 + hyperleptinemia), “healthy” (BMI≥25 kg/m2 , without hyperleptinemia), “hidden” or “latent” (BMI&lt;25 kg/m2 + hyperleptinemia), as well as “normal weight” (BMI&gt;&lt;25 kg/m2 , without hyperleptinemia).&gt;˂ 25 kg/m2 + hyperleptinemia), as well as “normal weight” (BMI˂ 25 kg/m2 , without hyperleptinemia).Results. The “classic” phenotype of obesity/overweight was diagnosed in 22 (43%) patients, the “healthy” – in 1 (2%), the “hidden” – in 14 (27.5%) patients with SLE. Insulin concentrations were: 10.0 [7.5; 17.9] μU/mL in the “classic” phenotype, 8.3 [6.0; 11.9] μU/mL in the “hidden” phenotype, and 5.3 [4.2; 6.3] μU/ml at “normal weight” (p=0.001). HOMA-IR index were: 2.18 [1.70; 4.23], 1.78 [1.23; 2.41] and 1.18 [0.95; 1.52], respectively (p=0.002). The levels of glucose, total cholesterol, ApoB did not differ in the groups. The uric acid concentrations were the highest in the “classic” phenotype group (334 [365; 388] μmol/l), the lowest in the group of “hidden” obesity/overweight (257 [214; 296] μmol/l), and intermediate in “normal weight” group (286 [236; 377] μmol/l) (p=0.04).Conclusion. The majority of SLE patients hade the “classic” obesity/overweight phenotype, while the “healthy” phenotype was extremely rare. In 27.5% of patients, the presence of a “latent” phenotype was confirmed, which, in terms of metabolic disorders, is an intermediate stage between “normal weight” and “classic” obesity. For rational and timely prevention of insulin resistance, metabolic syndrome and related complications, it is necessary to actively identify the “hidden” phenotype.

1272-P: Genomic Rearrangement in Noncoding Region of Chromosome 1 Leads to Spontaneous Obesity and Type 2 Diabetes

Obesity is a major health risk for type 2 diabetes, along with many other disease conditions. We discovered spontaneous obese mice among a conditional transgenic mouse line (Floxed-stop Overexpression of IF1, or FEI) , which was originally generated and maintained for Cre-mediated conditional transgenic IF1 expression. Severe obesity became a fixed phenotype in FEI mice after inbreeding for 5-6 generations. Targeted-Locus-Amplification (TLA) analyses revealed that a rearrangement occurred in upstream sequences (48,224,9 to 48,248,586) of the transgenic integrated site, and are duplicated downstream at a non-coding region of chromosome 1. Early-onset obesity was consistent in both male and female FEI mice with progressive weight gain from 2 months and reached 50-60 grams at 6-8 months. Body composition analyses revealed that FEI mice have markedly increased fat mass and modestly increased lean mass compared to wild-type (WT) mice. Consistently, the FEI mice exhibited increased peripheral fat pads and dyslipidemia. The FEI mice exhibited increased food intake but reduced systemic metabolic rates. Moreover, we detected increased fed and fasting blood glucose, insulin, and leptin with impaired glucose and insulin tolerance in FEI mice as early as 6 weeks of age. Histology analyses with H&amp;E staining revealed markedly enlarged adipocytes with crown-like structures on visceral white adipose tissue sections and increased fat deposition in liver sections from FEI mice. RNAseq analyses on RNA samples from subcutaneous white adipose tissues demonstrate the upregulation of adipogenesis and inflammation genes. These results indicate that the FEI mouse line is a novel obese mouse model with genomic rearrangement in a non-coding region, which may serve as cis-regulatory elements for obese genes. Further studies on these mice should yield novel and translational insight into the molecular and metabolic mechanisms underlying obesity development with complex genetic traits. Disclosure D.White: None. J.Wu: None. L.Lauterboeck: None. S.Kang: None. M.Elgazzaz: None. S.Alahari: None. E.D.Lazartigues: None. Q.Yang: None.

1046-P: Role of Serum C1q/TNF-Related Protein 9 in Predicting Gestational Diabetes Mellitus

Background/Aims: C1q/TNF-related protein 9 (CTRP9) as a member of CTRP super family, participates in the regulation of glycolipid metabolism. However information regarding the role of CTRP9 in gestational diabetes mellitus (GDM) is scarce. The current study aims to ascertain the relationship between serum CTRP9 levels and GDM. Methods: A total of 35 GDM patients and 37 normal pregnant women were enrolled in our study. Serum CTRP9 levels were measured via enzyme-linked immunosorbent assay (ELISA) . Fasting insulin (FINS) , IL-6, Leptin, MCP-1, TNF-α and IL-1β were quantified using Luminex-xMAP technology. Anthropometric data and biochemical parameters were also obtained or measured. Results: The results showed that fasting plasma glucose (FPG) , one hour plasma glucose (1-h PG) , 2 hour plasma glucose (2-h PG) , FINS, IL-6, Leptin, TNF-α and CTRP9 during GDM group were significantly higher than the control group. In addition, serum CTRP9 levels had a significantly positive correlation with FPG (r = 0.559, P &amp;lt; 0.001) , 1h-PG (r = 0.539, P &amp;lt;0.0) , 2h-PG (r = 0.378, P = 0.001) , FINS (r = 0.253, P = 0.032) , HOMA-IR (r = 0.382, P = 0.001) , IL-6 (r = 0.283, P = 0.016) , and TNF-α (r = 0.266, P = 0.024) . Furthermore, binary logistic regression demonstrated that HOMA-IR and CTRP9 were independent risk factors for GDM. The AUC-ROC indicated that the diagnostic efficiency of combined CTRP9 and HOMA-IR was much higher than a single index. Conclusions: The high level of serum CTRP9 is an independent risk factor for GDM. Moreover, the combination of serum CTRP9 and HOMA-IR were more efficient in diagnosing GDM. Key words: Gestational diabetes mellitus, CTRP9, insulin resistance Disclosure H. Zhang: None.

Fasting levels of appetite regulating hormones predict caloric intake at breakfast in a group of Chilean adolescents.

Appetite regulation is integral to food intake and is modulated by complex interactions between internal and external stimuli. Hormonal mechanisms which stimulate or inhibit intake have been characterized, but the physiologic effects of serum levels of such hormones in short-term appetite regulation have received little attention. To evaluate whether fasting levels of orexigenic/anorexigenic hormones were associated with energy intake at breakfast, served soon after drawing a fasting blood sample, in a group of adolescents. Anthropometry, body composition and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured in 655 Chilean adolescents aged 16.8 ± 0.3 years (52% males). Energy intake was measured at a semi-standardized breakfast. Associations between hormone levels and energy intake were studied using multivariate linear models. Thirty nine percent of participants were overweight/ obese. After an overnight fast, median values for leptin, insulin, ghrelin and orexin-A were 7.3 ng/mL, 6.7 IU/dL, 200.8 pg/mL, and 16.1 pg/mL, respectively. Participants ate on average 637 ± 239 calories at breakfast. In multivariable models, insulin levels were inversely and independently associated with caloric intake at breakfast (β = -18.65; p < 0.05), whereas leptin, ghrelin and orexin-A levels were positively and independently associated with intake: β= 5.56, β = 0.34 and β = 8.40, respectively, p < 0.05. Fasting leptin, ghrelin and orexin-A were positively associated with energy intake during breakfast provided soon after the blood draw. Insulin was negatively associated with energy intake. Modifiable factors influencing levels of appetite regulating hormones could be a potential target for influencing food intake.

MicroRNA profiling and the effect on metabolic biomarkers and weight loss after laparoscopic sleeve gastrectomy: A prospective cohort study

Background: Epigenetic changes after bariatric surgery are of increasing interest; we evaluated the levels of two circulating microRNAs (miRNA-222 and miRNA-146a) before and after the laparoscopic sleeve gastrectomy (LSG) and the effect of weight loss on the levels of metabolic biomarkers. Materials and Methods: We prospectively evaluated patients pre- and 12 months post-LSG for percent excess weight loss (%EWL), miRNAs levels, metabolic biomarkers (leptin, ghrelin, peptide YY, and glucagon peptide-1 [GLP-1]) levels from August 2019 to September 2021. Results: Significant differences were observed in the miRNA146a-3p (median: 0.64 (0.012-2.68) vs. 1.07 (0.1-3.6); P = 0.019) and miRNA222-5p (median 1.80 (0.1–3.61) vs. 1.19 (0.1-3.68); P = 0.003) levels before and after (12 months) LSG; fasting leptin, ghrelin, insulin, total cholesterol, high- and low-density lipoproteins, fasting blood sugar (FBS), and triglyceride levels also showed significant differences. Significant changes were observed in postprandial values of glucagon-like peptide l (GLP-1) (P = 0.0001) and peptide YY (P = 0.0006) 12 months after LSG. Homeostatic model assessment of insulin resistance (IR) was significantly correlated with %EWL, miRNA146a, and miRNA222-5p (P = 0.002). Postoperatively measured miR146a-39 and miRNA222-5p showed significant coefficient of determination R2 of 0.184 (P = 0.008) and 0.259, P = 0.0007 toward %EWL, respectively. Furthermore, significant correlations of miRNA146a were observed with FBS and IR. Conclusions: LSG-mediated weight loss affected the plasma levels of miR146a and miR222-5p. Due to the simultaneous decrease of ghrelin and increase of postprandial hormones (peptide YY and GLP-1), medical problems in patients with obesity were reduced. This study identified miRNAs as the new markers in the treatment, diagnosis, and therapeutic direction of patients with obesity.

Abstract 13471: HFpEF in Spontaneously Obese Mice Due to Genomic Rearrangement in Non-Coding Region of Chromosome 1

Background: Obesity is the most common comorbidity and risk factor for heart failure (HF) in patients with preserved ejection fraction (HFpEF), a subclass containing more than 50% of HF cases. However, effective treatment of HFpEF remains scarce due to the incomplete understanding of the mechanisms. Methods: A mouse line (C57/B6J) of Floxed-stop Overexpression of IF1 (FEI) was generated and maintained for Cre-mediated conditional IF1 overexpression. We observed that severe obesity became a fixed phenotype in inbred FEI mice after inbreeding for 5-6 generations. Targeted-Locus-Amplification (TLA) analyses revealed that FEI inbreeding triggered a genomic rearrangement in a non-coding region of chromosome 1. A heterozygous line with genotype and phenotype fixation was obtained via outbreeding with wild type mice. In the present study, we focus on assessing the cardiac phenotype of FEI mice using echocardiography, histology, and exercise tolerance tests. Results: The early onset of obesity was consistent in the heterozygotes of obese FEI mice with increased peripheral fats and circulating tissue lipids, as well as reduced systemic metabolic rates. FEI mice also exhibited increased food intake, fasting blood glucose, insulin, and leptin with impaired glucose/insulin tolerance. Echocardiography revealed that the FEI mice developed concentric left ventricular hypertrophy with preserved ejection fraction. However, E/A ratio results from Doppler flow measurement at mitral valve suggest diastolic dysfunction in the FEI mice. Heart weight to tibial length ratio was significantly increased in FEI compared with WT mice. H&amp;E and Trichrome blue staining on heart sections exhibited increased cardiomyocyte hypertrophy and cardiac fibrosis. Treadmill exercise tolerance test revealed a significantly decreased exercise tolerance in FEI mice. Conclusions: We conclude that the cardiac phenotypes in the obese FEI mice closely recapitulate obese patients who suffer from HFpEF. Thus, further studies on these mice should yield novel and translational insight into the molecular and metabolic mechanisms underlying the HFpEF development, leading to improved treatments.

Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy.

Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

The association between body composition, leptin levels and glucose dysregulation in youth with cystic fibrosis

BackgroundOptimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls. MethodsIn a cross-sectional study, 59 adolescents and young adults with CF and 15 healthy controls matched by age and gender, underwent body composition analysis using dual energy X-ray absorptiometry (DXA) and a 2-hour oral glucose tolerance test (OGTT). Measures of insulin sensitivity, β-cell insulin secretion and fasting leptin levels were obtained. ResultsOf the participants with CF, 62% were classified as abnormal glucose tolerant and 22% with cystic fibrosis related diabetes (CFRD). Patients with CFRD had a lower fat mass index (FMI) z-score, wt z-score and leptin levels compared to the control group (-1.86 vs. - 0.59, p=0.01; -1.86 vs 0.44, p=<0.001 and 7.9 vs vs. 27.7 µg/L, p=0.01). Leptin correlated positively with FMI z-score, BMI, weight z-score and indices of insulin secretion. FMI z-score correlated positively with higher insulin resistance (HOMA-IR), and lower insulin sensitivity (Matsuda index) (r=0.31; p =0.01 and r=-0.29; p=0.02, respectively) in the CF group. ConclusionsThis study shows that despite new therapeutic strategies, youth with CF have lower body fat, weight z-score and leptin levels, particularly in subjects with early onset CFRD.

Bariatric surgery restores visual cortical plasticity in nondiabetic subjects with obesity.

Obesity leads to changes in synaptic plasticity. We aimed at investigating the impact of bariatric surgery (RYGB) on visual neural plasticity (NP) and its relationship with the main gut peptides, leptin, and brain-derived neurotrophic factor (BDNF). NP was assessed testing binocular rivalry before and after 2 h of monocular deprivation (index of visual brain plasticity) in 15 subjects with obesity (age 42.3 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) before and after RYGB. Gut peptides, leptin, and BDNF were obtained at baseline and 6 months after surgery in 13 subjects. A significant reduction in BMI (p < 0.001 vs. baseline) and a significant increase of disposition index (DI, p = 0.02 vs baseline) were observed after RYGB. Total and active GLP-1 release in response to glucose ingestion significantly increased after RYGB, while no changes occurred in VIP, GIP, and BDNF levels. Fasting leptin concentration was lower after RYGB (p = 0.001 vs. baseline). Following RYGB, NP was progressively restored (p < 0.002). NP was correlated with DI and fasting glucose at baseline (r = 0.75, p = 0.01; r = -0.7, p = 0.02; respectively), but not with BMI. A positive correlation between post-pre-RYGB changes in AUCactive GLP-1 and NP was observed (r = 0.70, p < 0.01). Leptin was inversely correlated with NP 6 months after surgery (r = -0.63, p = 0.02). No correlation was observed between GIP, VIP, BDNF, and NP. Visual plasticity is altered in subjects with obesity, and it can be restored after RYGB. The improvement may be mediated by amelioration of insulin sensitivity, increased GLP-1 levels, and reduced leptin levels.

A Novel Variant of the SH2B1 Gene in an Obese Child With Type 2 Diabetes

Obesity in children and adolescents is at epidemic levels in the United States and creates high risk for comorbidities later in life. Childhood obesity is thought to be the result of behavioral and nutritional problems. Although genetic factors may play a role in the etiology of obesity, monogenic forms of obesity are rare. We present a child with obesity, behavioral problems, leptin resistance, and type 2 diabetes who also carries a mutation of Sarcoma Homologous 2B adapter protein 1 (SH2B1). The subject was evaluated at 13 7/12 years old. He had polyphagia, learning disability, aggressive behavior and marked obesity. At ages 9,11, and 13 years respectively, his BMI was 9%, 16%, and 52% above the 95th percentile. At 13 7/12 years old, his height was at the 80th percentile and BMI was 66% above the 95th percentile. He had marked acanthosis nigricans and he was prepubertal. Fasting blood glucose and insulin levels were 116 mg/dl and 592 mIU/L, respectively. Hemoglobin A1c was 6.5% and metformin therapy was initiated for type 2 diabetes. Fasting leptin level (41.5 ng/mL) was markedly elevated indicating leptin resistance. DNA methylation study excluded Prader-Willi syndrome. DNA sequencing indicated a novel heterozygous c.1555G>T variant of SH2B1 gene, which is predicted to result in the amino acid substitution p. Asp519Tyr. The analysis by PolyPhen-2 and MutationTaster predicts that the variant is a pathogenic mutation affecting protein functions. SH2B1 interacts with JAK2 and may play a role in insulin signaling. Pathogenic heterozygous variants in SH2B1 have been associated with obesity, insulin resistance and maladaptive behavior phenotypes (Pearce et al, 2014). Sh2b1-null mice develop severe leptin resistance, obesity, and type 2 diabetes. Our report underscores the importance of investigating monogenic causes of obesity in subjects who present severe obesity, diabetes, and behavioral problems. Additional studies are needed to determine the association between this novel mutation and the clinical features of this patient.

Maternal glucose in pregnancy is associated with child's adiposity and leptin at 5 years of age.

Exposure to maternal hyperglycaemia in pregnancy has been associated with childhood obesity. Leptin regulation might be involved in this 'adiposity programming' and may depend on timing of exposure. To investigate associations of maternal glycaemia at different periods in pregnancy with childhood adiposity and leptin levels at 5 years of age. In a prospective pre-birth cohort, we measured maternal glucose levels after a 50 g oral glucose challenge test at first trimester (9.8± 2.3 weeks) and during a 75 g oral glucose tolerance test at second trimester (26.5± 0.9 weeks). We followed up children at 5 years; we measured anthropometry and body composition using dual-energy X-ray absorptiometry (DXA). We measured fasting leptin levels using immunoassays (Luminex) in 328 children. We conducted linear regression analyses, adjusting for potential confounders. Maternal glycaemia at first trimester was associated with childhood leptin levels at 5 years, independently of maternal pre-pregnancy BMI and other confounders (β= .09 ± .04; P= .03). Higher post-load glucose levels at second trimester were associated with greater total body fat percentage measured by DXA (1hour-glucose: β= .010 ± .004; P= .03 and 2hours-glucose: β= .016 ± .005; P= .002), but not with leptin levels. Our results suggest that programming of leptin regulation may be sensitive to maternal hyperglycaemia specifically in early pregnancy.

Fasting leptin and acyl ghrelin levels in obese and lean female

Fasting leptin and acyl ghrelin levels in obese and lean female