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Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans
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DOI：10.1210/clinem/dgac699.png)
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Abstract
En 中文
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 (beta [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.
Keywords:
hyperglycemia
hyperinsulinemia
leptin signaling
obesity
soluble leptin receptor
Journal
J
IF:
5.1
Papers:
2.1W
Citations:
7.9W