Ghrelin and its endogenous antagonist liver‐expressed antimicrobial peptide‐2 (LEAP‐2) are involved in GH secretion and glucose/lipids metabolism. LEAP‐2 expression in conditions of metabolic impairment may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Adult growth hormone deficiency (aGHD) is characterized by insulin resistance, weight gain, and increased fat mass. Therefore, the primary endpoint of this cross‐sectional observational pilot study was to compare circulating LEAP‐2 and ghrelin levels in aGHD and healthy controls. Thirty patients were included in the study. Group A included adult GHD: 15 patients, 8 females, and 7 males. Median and interquartile range age of the group was 53 (41–57) years, while BMI was 27.1 (25–35) kg/m2. Group B was formed by 15 healthy controls (10 females and 5 males). Median and interquartile range age was 47 (36–57) years, while BMI 22.9 (20.8–33.1) kg/m2. They were evaluated for serum glucose and insulin, HOMA‐index, QUICKI‐index, total/LDL/HDL cholesterol, triglycerides, IGF‐1, ghrelin, and LEAP‐2. Ghrelin levels in the aGHD group were significantly lower than in healthy controls. In contrast, LEAP‐2 showed a trend toward higher levels, although the differences were not significant. However, the LEAP‐2/Ghrelin ratio was significantly higher in aGHD. No significant correlations between ghrelin and LEAP‐2 with BMI and HOMA index were found in aGHD population. However, a significant inverse correlation (r2 = 0.15, p = .047) between BMI and ghrelin was evidenced when considering the whole population. Taken together, these results may suggest a body adaptation to a metabolic scenario typical of aGHD. The decrease in ghrelin production could prevent further weight gain and fat mass increase, although losing its secretagogue effect.
Neudesin, a newly discovered peptide mainly secreted in brain and adipose tissue, is under evaluation for its possible activity as negative regulator of energy expenditure. In pre-adipocyte cultures neudesin promotes adipogenesis, while in mice model neudesin decreases food intake. Childhood overweight and obesity are among the main health issues in modern times, especially in western countries, due to the association to increased cardiovascular and oncological risk in adult age. No data on neudesin in obese and overweight children are currently available. Given that, we aim to perform an observational cross-sectional study testing the hypothesis that neudesin plasmatic levels may be affected in obese and overweight children. We also evaluated any eventual relationship between neudesin and metabolic and anthropometric parameters to gain insight on a possible role in childhood obesity. 34 children were included in the study and divided in two groups according to Cole's criteria. Group A included obese and overweight children, 23 patients, 17 females (Tanner stage 1) and 6 males, aged 4-10 years; Group B included normal-weight children, 11 patients, 7 females (Tanner stage 1) and 4 males, aged 3-10 years. Metabolic (glucose and insulin, total - LDL - HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters were evaluated. HOMA index, QUICKI index and the area under the curve (AUC) of glucose and insulin after oral glucose load were calculated in obese and overweight children. Neudesin was measured by ELISA system. Neudesin levels did not significantly differ between the two groups, even though a trend toward higher levels in group A was found (mean±SEM 3±0.32 ng/ml vs 1.98±0.15 ng/ml, p = 0.1). As expected, obese and overweight children showed significantly higher blood glucose, total and LDL cholesterol, triglycerides and leptin levels than those with normal weight. Interestingly, in obese and overweight children plasmatic neudesin levels significantly directly correlated with blood glucose and AUC of glucose. No other new significant correlation was detected in both groups. Very few data on serum neudesin levels in human are available. To note, neudesin was lower in obese adolescents compared to age-matched normal controls (1), while children affected by type 1 diabetes mellitus showed higher levels than age-matched controls (2). Taken together, these results, although preliminary, may suggest a possible age-related role of neudesin in glucose homeostasis in obese/overweight children. References 1. Celikkol A. et al, J Clin Res Pediatr Endocrinol, 2021 2. Polkowska A. et al, Biomed Res Int, 2019 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
Liver enriched antimicrobial peptide-2 (LEAP-2) is an endogenous antagonist of ghrelin, which acts as an allosteric modulator of growth hormone secretagogue receptors. It is expressed predominantly in liver, followed by kidney, jejunum, duodenum and stomach. Its expression in conditions of metabolic impairment, obesity for instance, may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Weight gain and hyperglycaemia seem to be the main trigger factors for LEAP-2 production. Adult growth hormone deficiency (aGHD) is known as a pathological condition characterized by metabolic impairment (insulin resistance, weight gain, increased fat mass, decreased lean mass). To the best of our knowledge, no study in literature deals with the problem of circulating LEAP-2 levels in GHD. Therefore, the primary endpoint of this cross-sectional observational study was to evaluate circulating LEAP-2 levels in GHD in comparison to healthy controls whether the secondary endpoint was to evaluate any possible correlation with IGF-1 and metabolic parameters in such condition. 30 patients were included in the study. Group A included adult GHD: 15 patients, 7 females and 8 males, mean±standard error of the mean (SEM) age 54.6±3.51 years, BMI 29,95±1.63 kg/m2). The etiologies of GHD were empty sella (n=6), idiopathic (n=6), post-surgical hypopituitarism (n=2), pineal cyst (n=1). Group B was formed by controls: 15 patients, 11 females and 4 males, mean±SEM age 40.33±2.61 years, BMI 24.19±1.33 kg/m2. They were evaluated for: serum glucose and insulin, HOMA-index, QUICKI-index, Total/LDL/HDL cholesterol, triglycerides, IGF-1 and LEAP-2 (measured using Human LEAP-2 ELISA kit, Phoenix Pharmaceuticals Inc, according to manufacturer’s instructions). Circulating LEAP-2 is significantly higher in GHD than in control group (26.98±3.12 vs 18.7±1.9 ng/ml, p=0.03). LEAP-2 levels in our cohort was not influenced by BMI, while a significant direct correlation between LEAP-2 and age was detected in aGHD group. A strong significative inverse correlation between LEAP-2 and IGF-1 was evidenced in aGHD (r2=0.5). Finally, in this group, LEAP-2 inversely correlates with total cholesterol (r2=0.45). As expected circulating LEAP-2 levels, in a condition of metabolic impairment such as GHD, were higher than controls even if no correlation with BMI was evidenced in our cohort. The inverse correlation between LEAP-2 and IGF-1 in GHD patients may suggest a body adjustment in a worse clinical condition. LEAP-2 may act as a brake for ghrelin production, thus preventing further weight gain and fat mass increase, although losing its secretagogue effect.
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