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Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans

The journal of clinical endocrinology and metabolism, 2023-05, Vol.108 (5), p.1110-1119 [Peer Reviewed Journal]

The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. 2022 ;The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. ;COPYRIGHT 2023 Oxford University Press ;info:eu-repo/semantics/openAccess ;ISSN: 0021-972X ;EISSN: 1945-7197 ;DOI: 10.1210/clinem/dgac699 ;PMID: 36459457

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Title:
Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans
Author: Sommer, Christine ; Vangberg, Kjersti G ; Moen, Gunn-Helen ; Evans, David M ; Lee-Ødegård, Sindre ; Blom-Høgestøl, Ingvild K ; Sletner, Line ; Jenum, Anne K ; Drevon, Christian A ; Gulseth, Hanne L ; Birkeland, Kåre I
Subjects: Body fat ; Body Mass Index ; Chemical industry ; Clinical ; Cross-Sectional Studies ; Denosumab ; Dextrose ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - epidemiology ; Enzyme-linked immunosorbent assay ; Enzymes ; Epidemiology ; Exercise ; Fasting ; Food intake ; Genetics ; Glucose ; Herbicides ; Humans ; Hyperglycemia ; Hyperinsulinemia ; Insulin ; Insulin Resistance - physiology ; Leptin ; Medical equipment and supplies industry ; Medical research ; Medical test kit industry ; Medicine, Experimental ; Monoclonal antibodies ; Pesticides industry ; Physical activity ; Physical fitness ; Physical training ; Receptors, Leptin ; Statistics ; Type 2 diabetes
Is Part Of: The journal of clinical endocrinology and metabolism, 2023-05, Vol.108 (5), p.1110-1119
Description: 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 (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]). 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.
Publisher: US: Oxford University Press
Language: English;Norwegian
Identifier: ISSN: 0021-972X
EISSN: 1945-7197
DOI: 10.1210/clinem/dgac699
PMID: 36459457
Source: NORA Norwegian Open Research Archives

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Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans

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