Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans.
J Clin Endocrinol Metab
; 108(5): 1110-1119, 2023 04 13.
Article
in En
| MEDLINE
| ID: mdl-36459457
ABSTRACT
CONTEXT Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown. OBJECTIVE:
This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity.METHODS:
We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization.RESULTS:
In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (ß [95% CI] -0.19 [-0.21 to -0.17]), body fat (-0.12 [-0.14 to -0.10), and fasting C-peptide (-2.04 [-2.46 to -1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58], and -0.20 [-0.36 to -0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R.CONCLUSION:
BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Diabetes Mellitus, Type 2
Type of study:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2023
Document type:
Article
Affiliation country: