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The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various molecules involved in bone remodeling in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic (ND) and 104 T2D. A Multiplex assay was used to assess the level of various osteogenic molecules namely osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to ND individuals (p ≤ 0.05). Using Spearman’s correlation, a positive correlation was observed between irisin and Osteoactivin as well as OPG (p < 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p < 0.05). The strong positive association shown in this study between irisin, METRNL and various molecules with osteogenic properties emphasize a possible interaction between these organs. This report suggests that having a dysregulation in the level of the aforementioned molecules could potentially affect the development of bone and muscle related complications that are associated with obesity and T2D.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p < 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p < 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

Background Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3). Objectives To study the effect of SG on the levels of proteins involved in thermogenesis process. Setting Laboratory rats at Kuwait University. Methods Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet “high-fat/carbohydrate diet” ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation. Results The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue. Conclusions Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.

Obesity and type 2 diabetes (T2D) are linked to metabolic dysregulation and chronic inflammation. Adipose tissue and skeletal muscles are key endocrine organs. Dysregulation in adipomyokines secreted by these organs could play a role in obesity-induced complications. Obesity, T2D and bone metabolism are interrelated. Our objective was to study the expression of two adipomyokines-Irisin and Meteorin-like protein (METRNL) in obesity and T2D and understand their association with various bone markers. Overall, 228 individuals were enrolled in this study, including 124 nondiabetic and 104 T2D . Plasma level of MTRNL and irisin were assessed by ELISA. Plasma level of METRNL and irisin were significantly higher in T2D (1263.5 ± 24.9 pg/ml and 623.0± 21.8 pg/ml respectively) compared to nondiabetic individuals (1198.5 ± 24.2 pg/ml for METRNL and 508.2 ± 15.3 pg/ml for irisin) p-Value < 0.05. METRNL and irisin were significantly higher in obese (1267.9 ± 24.8 pg/ml and 593.4 ± 18.1 pg/ml respectively) compared to non-obese individuals (1186.3 ± 24.2 pg/ml and 519.9 ± 19.1 respectively) p-Value < 0.05. Plasma level of bone markers Osteoactivin, Syndecan, OPG and SPARC were significantly higher in obese and T2D individuals compared to non-obese and nondiabetic individuals (P-values ≤0.01). Correlation analysis on nondiabetic population showed significant positive correlation between METRNL and irisin. Irisin showed a strong positive association with Osteoactivin, Syndecan, OPG, and SPARC. A strong positive association was observed between METRNL and Osteoactivin. The interplay between these bone markers is linked to bone remodeling. The strong positive association between the adipomyokines and bone markers suggests that, a dysregulation in the functional interaction between them may play a possible role in the development of bone related complications associated with obesity and T2D. We are currently conducting further experiments to understand mechanistically the significance of their interplay. Disclosure M. Abu-farha: None. P.T. Cherian: None. I. Al khairi: None. M. Jamal: None. S. Al-Sabah: None. H. Ali: None. C. Dsouza: None. F.K. AlOtaibi: None. W. Al-Ali: None. G.M. Al-Khaledi: None. J. Abubaker: None. F. Al-Mulla: None. Funding Dasman Diabetes Institute