The following is a summary of “Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans,” published in the May 2023 issue of Endocrinology & Metabolism by Sommer, et al.

For a study, researchers sought to examine the impact of various factors, including glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity, on serum soluble leptin receptor (sOb-R) levels, and to investigate the potential causal relationships with type 2 diabetes (T2D).

A comprehensive analysis was conducted using a combination of cross-sectional, interventional, and Mendelian randomization study designs. Serum or plasma sOb-R levels were measured using commercial enzyme-linked immunosorbent assay kits with monoclonal antibodies in five independent clinical studies involving a range of participants (from 24 to 823). Mixed-model regression and 2-sample Mendelian randomization analyses were utilized.

Pooling the cross-sectional data, adjusting for study variations, revealed an inverse association between sOb-R levels and BMI (β [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]). In interventional studies, acute hyperinsulinemia during euglycemic glucose clamp led to a decrease in sOb-R levels in two independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), while intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]) immediately increased sOb-R levels. Mendelian randomization analysis indicated that higher fasting insulin levels and BMI causally contributed to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58] and -0.20 [-0.36 to -0.04], respectively). However, the relationship between hyperglycemia and sOb-R levels was inconsistent in cross-sectional studies and not significant in interventional studies. Mendelian randomization analysis did not support a causal effect of fasting glucose on sOb-R levels.

The findings suggested that BMI and insulin levels have a causal effect on reducing serum sOb-R levels, indicating potential involvement in the regulation of leptin signaling. Additionally, acute intensive exercise and food intake were associated with an immediate increase in sOb-R levels. The results highlighted the role of sOb-R in the short-term regulation of leptin signaling, either directly or indirectly, and propose that hyperinsulinemia may dampen leptin signaling. Further investigation was needed to fully elucidate the underlying mechanisms and long-term implications of sOb-R in T2D.

Source: academic.oup.com/jcem/article/108/5/1110/6865288