Intervertebral Disc and Adipokine Leptin—Loves Me, Loves Me Not

Ćurić, Goran

doi:10.3390/ijms22010375

Cited by 7 publications

(3 citation statements)

References 95 publications

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“…It also indicated that being overweight may have a modifying effect on SNP associations, which leads to a loss of the protective effect attributed to the alleles on the studied genes. However, based on a recent review by Curic, we cannot conclude whether detrimental and beneficial effects of the LEP variant exist in IVDD [ 73 ]. We suggest that detailed functional studies should be performed to investigate and understand the role of these SNPs in patients with IVDD, as well as the SNPs’ association with serum leptin levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration

Chen

Hsu

Liao

et al. 2022

IJMS

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Intervertebral disc degeneration (IVDD), for which obesity and genetics are known risk factors, is a chronic process that alters the structure and function of the intervertebral discs (IVD). Circulating leptin is positively correlated with body weight and is often measured to elucidate the pathogenesis of IVD degeneration. In this study, we examined the associations of LEP single nucleotide polymorphisms (SNPs) genetic and environmental effects with IVDD. A total of 303 Taiwanese patients with IVDD (mean age, 58.6 ± 12.7 years) undergoing cervical discectomy for neck pain or lumbar discectomy for back pain were enrolled. Commercially available enzyme-linked immunosorbent assay (ELISA) kits measured the circulating plasma leptin levels. TaqMan SNP genotyping assays genotyped the LEP SNPs rs2167270 and rs7799039. Leptin levels were significantly increased in obese individuals (p < 0.001) and non-obese or obese women (p < 0.001). In the dominant model, recoded minor alleles of rs2167270 and rs7799039 were associated with higher leptin levels in all individuals (p = 0.011, p = 0.012). Further, the association between these LEP SNPs and leptin levels was significant only in obese women (p = 0.025 and p = 0.008, respectively). There was an interaction effect between sex and obesity, particularly among obese women (interaction p = 0.04 and 0.02, respectively). Our findings demonstrate that these SNPs have sex-specific associations with BMI in IVDD patients, and that obesity and sex, particularly among obese women, may modify the LEP transcription effect.

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Section: Discussionmentioning

confidence: 99%

Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration

Chen

Hsu

Liao

et al. 2022

IJMS

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“…Leptin, beyond its well-known role in energy regulation and appetite control, influences various systemic functions, including immune response modulation, bone formation, and reproductive health (Francisco et al, 2018). In the musculoskeletal system, leptin affects chondrocyte proliferation, osteoblast activity, the synthesis of extracellular matrix proteins, and many more tissue-and cell-level functions crucial for maintaining homeostasis (Gruber et al, 2007;Li et al, 2013;Han et al, 2018;Sharma, 2018;Segar et al, 2019;Curic, 2021). Leptin's responsibilities in the IVD specifically include promoting anabolic processes and reducing catabolic activities, thereby supporting disc health (Li et al, 2013;Han et al, 2018).…”

Section: {Figure 1}mentioning

confidence: 99%

Secreted chemokines reveal diverse inflammatory and degenerative processes in the intervertebral disc of the STZ-HFD mouse model of Type 2 diabetes

Gonzalez,

Vaidya,

Clayton

et al. 2024

Preprint

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The chronic inflammation present in type 2 diabetes causes many chronic inflammatory comorbidities, including cardiovascular, renal, and neuropathic complications. Type 2 diabetes is also associated with a number of spinal pathologies, including intervertebral disc (IVD) degeneration and chronic neck and back pain. Although confounding factors such as obesity are thought to increase the loads to the musculoskeletal system and subsequent degeneration, studies have shown that even after adjusting age, body mass index, and genetics (e.g. twins), patients with diabetes suffer from disproportionately more IVD degeneration and back pain. Yet the tissue-specific responses of the IVD during diabetes remains relatively unknown. We hypothesize that chronic diabetes fosters a proinflammatory microenvironment within the IVD that accelerates degeneration and increases susceptibility to painful disorders. To test this hypothesis, we evaluated two commonly used mouse models of diabetes – the leptin-receptor deficient mouse (db/db) and the chronic high-fat diet in mice with impaired beta-cell function (STZ-HFD). The db/db is a genetic model that spontaneous develop diabetes through hyperphagia, while the STZ-HFD mouse first exhibits rapid obesity development under HFD and pronounced insulin resistance following streptozotocin administration. Both animal models were allowed to develop sustained diabetes for at least twelve weeks, as defined by elevated hemoglobin A1C, hyperglycemia, and glucose intolerance. Following the twelve-week period, the IVDs were extracted in quantified in several measures including tissue-specific secreted cytokines, viscoelastic mechanical behavior, structural composition, and histopathologic degeneration. Although there were no differences in mechanical function or the overall structure of the IVD, the STZ-HFD IVDs were more degenerated. More notably, the STZ-HFD model shows a significantly higher fold increase for eight cytokines: CXCL2, CCL2, CCL3, CCL4, CCL12 (monocyte/macrophage associated), IL-2, CXCL9 (T-cell associated), and CCL5 (pleiotropic). Correlative network analyses revealed that the expression of cytokines differentially regulated between the db/db and the STZ-HFD models. Moreover, the STZ-HFD contained a fragmented and modular cytokine network, indicating greater complexities in the regulatory network. Taken together, the STZ-HFD model of type 2 diabetes may better recapitulate the complexities of the chronic inflammatory processes in the IVD during diabetes.

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“…Intervertebral disc degeneration (IDD) is a complex and multifactorial process influenced by aging, lifestyle, high mechanical load, infection, obesity, and heredity. [1][2][3][4][5][6] These initialization factors, such as annulus fibrosus rupture and nucleus pulposus protrusion, lead to morphological changes. With the rapid development of molecular biology and molecular immunology and the in-depth study of cytokines and inflammatory mediators, more and more attention has been paid to the role of cytokines and inflammatory mediators in IDD.…”

Section: Introductionmentioning

confidence: 99%

Preoperative Lymphocyte to Monocyte Ratio as a Predictive Biomarker for Disease Severity and Spinal Fusion Failure in Lumbar Degenerative Diseases Patients Undergoing Lumbar Fusion

Guo¹,

Zhao²,

Lu³

et al. 2022

JPR

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Objective This study was designed to determine whether lymphocyte to monocyte ratio (LMR) correlated with the intervertebral disc degeneration (IDD) severity and the postoperative spinal fusion rate in patients with lumbar disc disease. Methods 303 patients undergoing posterior lumbar decompression and fusion were retrospectively analyzed. An examination of the blood count was performed before surgery. The cumulative grade was calculated by summing the pfirrmann grades of all lumbar discs. Grouping was based on the 50th percentile of cumulative grade and spinal fusion. The relationship between LMR and IDD severity and spinal fusion was explored using correlation analyses and logistic regression models. The receiver operating characteristic (ROC) curve was performed to measure model discrimination, and Hosmer-Lemeshow (H-L) test was used to measure calibration. Meanwhile, the ROC curve evaluated the discrimination ability of LMR in predicting severe degeneration and fusion failure. Results LMR was significantly lower in the severe degeneration group (cumulative grade > 18) than in the mild to moderate degeneration group (cumulative grade ≤ 18). Furthermore, the LMR of the fusion group was significantly higher than that of the non-fusion group. The multivariate binary logistic models revealed that LMR was an independently influencing factor of the severe degeneration and fusion failure (OR: 0.793, 95% CI: 0.638–0.987, p = 0.038; OR: 0.371, 95% CI: 0.258–0.532, p < 0.001). The models showed excellent discrimination and calibration. The area under the curve (AUC) of severe degeneration and fusion failure identified by LMR were 0.635 and 0.643, respectively, and the corresponding cut-off values were 3.16 and 3.90. Conclusion LMR is significantly associated with the risk of severe disc degeneration and spinal fusion failure.

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Intervertebral Disc and Adipokine Leptin—Loves Me, Loves Me Not

Cited by 7 publications

References 95 publications

Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration

Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration

Secreted chemokines reveal diverse inflammatory and degenerative processes in the intervertebral disc of the STZ-HFD mouse model of Type 2 diabetes

Preoperative Lymphocyte to Monocyte Ratio as a Predictive Biomarker for Disease Severity and Spinal Fusion Failure in Lumbar Degenerative Diseases Patients Undergoing Lumbar Fusion

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