Variation in glucocorticoid sensitivity and the relation with obesity

Abstract

Summary Increasing evidence points to a relation between increased glucocorticoid (GC) exposure and weight gain. In support, long‐term cortisol measurements using hair analysis revealed that many individuals with obesity appear to have cortisol values in the high physiological range. The mechanisms behind this relationship need to be determined in order to develop targeted therapy to reach sustainable weight loss in these subgroups. The effect of GCs is not only determined by the plasma concentration of GCs but also by individual differences in GC sensitivity and the target tissue, which can be analyzed by functional GC assays. GC sensitivity is influenced by multiple genetic and acquired (e.g., disease‐related) factors, including intracellular GC availability, hormone binding affinity, and expression levels of the GC receptors and their isoforms, as well as factors involved in the modulation of gene transcription. Interindividual differences in GC sensitivity also play a role in the response to exogenous GCs, with respect to both therapeutic and adverse effects. Accordingly, in this review, we summarize current knowledge on mechanisms that influence GC sensitivity and their relationships with obesity and discuss personalized treatment options targeting the GC receptor.

The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study

“…In addition, the parameters related to increased cardiovascular risk were associated with the presence and titer of anti-dsDNA antibodies, and the relationship was independent of the other cardiovascular risk factors ( Patiño-Trives et al, 2021 ). Certainly, glucocorticoid exposure may also play an important role in CVDs, for example, the high-dose of prednisolone promote carotid intima-media thickness progression in SLE ( Ajeganova et al, 2020 ; Lengton et al, 2021 ). It is still noteworthy that the use of glucocorticoid in SLE should be deserved attention due to the side effects of glucocorticoid in the cardiovascular risk.…”

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“…Exogenous corticoids are given to treat a broad range of immunological disorders, with similar biological effects to endogenous cortisol. 53 It is well-recognized that high glucocorticoid levels can lead to obesity, upregulate adipogenesis, and impact adipocyte metabolism. 54 In the acute setting, glucocorticoids inhibit anabolic processes and mobilize energy stores, promoting lipolysis.…”

“…Glucocorticoids are steroid hormones known for their anti‐inflammatory and immunosuppressive activity. Exogenous corticoids are given to treat a broad range of immunological disorders, with similar biological effects to endogenous cortisol 53 …”

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“…Elevated levels of glucocorticoids are directly related to weight gain. Therefore, it is advisable to analyze the mechanisms of this relationship to develop a therapeutic correction to achieve sustainable weight loss [ 23 ].…”