LEAP‐2/ghrelin interplay in adult growth hormone deficiency: Cause or consequence? A pilot study

Abstract

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.

Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline

“…One potential explanation of the limited impact of body weight is that none of the participants in current study carried a diagnosis of obesity and, instead, had BMIs within a lower and relatively narrow range. In addition, participants with metabolic disorders such as diabetes, hyperlipidemia, and hypercholesterolemia, as well as thyroid and hypothalamic disorders that may potentially affect LEAP2 regulation ( 72 , 73 ), were excluded. Whether this age-related upward shift in the LEAP2/ghrelin balance occurs as a natural defense against potentially deleterious, age-associated metabolic changes — perhaps at the expense of cognitive decline — is an interesting thought experiment.…”

Genetic variants of LEAP2 are associated with anthropometric traits and circulating insulin‐like growth factor‐1 concentration: A UK Biobank study

“…Notably, plasma concentrations of IGF-1 and LEAP2 increase during the pubertal growth spurt, and show a positive correlation in girls. 31 However, serum concentrations of LEAP2 and IGF-1 are not correlated in adults, 47,48 indicating that the link between these peptide hormones is dynamic and depends on the life stage. In this regard, it is interesting to mention that IGF-1 concentration is significantly associated with BMI in young (20-58 years) and old (67-86 years)…”

Preliminary study on the diagnostic value of LEAP-2 and CK18 in biopsy-proven MAFLD

“…In addition to metabolic diseases, it has also been found to be elevated in autoimmune diseases such as rheumatoid arthritis and is associated with inflammatory markers. Compared to healthy controls, the LEAP-2/Ghrelin ratio increases in patients with growth hormone deficiency [ 16 ]. Studies have also found that LEAP-2 is highly expressed in girls, especially those in the developmental stage (compared to males and pre-developmental females) [ 17 ].…”