Endocrines, Volume 6, Issue 1 (March 2025) – 4 articles

Background: Lipocalin 2 (LCN2), also known as neutrophil gelatinase-associated lipocalin, is a 25 kDa protein involved in immune defense, inflammation, and metabolism. Results: LCN2 is widely expressed across various tissues, including immune cells, bone, adipose tissue, liver, kidneys, lung, spleen, and epithelial cells, and exhibits sex- and fat depot-specific expression patterns. Structurally, LCN2 contains a hydrophobic lipid-binding pocket and glycosylation sites, enabling it to interact with diverse ligands and form dimers. In innate immunity, LCN2 plays a critical role by sequestering iron-laden siderophores, thereby restricting bacterial growth. Beyond its role in infection control, LCN2 is implicated in metabolic inflammation and diseases such as obesity and diabetes. Recent research has highlighted a pivotal role for LCN2 in mitochondrial phospholipid metabolism and mitochondrial function. In metabolic diseases and mitochondrial metabolism, LCN2 appears to display paradoxical effects. While some studies link it to improved insulin sensitivity, glucose regulation, and mitochondrial function, others associate it with insulin resistance, obesity, and mitochondrial dysfunction. These inconsistencies may arise from differences in experimental conditions and study populations. Conclusions: This review provides an up-to-date summary of LCN2’s multifaceted roles in obesity, diabetes, energy balance, and mitochondrial function, emphasizing its context-dependent effects. LCN2 appears to have dual roles, exerting both protective and detrimental outcomes depending on the physiological or pathological context, sex, cell types, and experimental conditions. Further research is necessary to unravel its complex functions and resolve conflicting findings, particularly in metabolic disorders. Full article

Background: Type 2 Diabetes (T2D) is increasingly becoming a critical healthcare priority globally. Medical interventions are primary strategies for managing diabetes, but more recently, diet/nutrition therapy, including the use of functional food products such as cinnamon and/or cinnamon products, has garnered considerable attention. The focus of this systematic review and meta-analysis is to examine whether cinnamon improves blood glucose parameters, body mass index, and inflammatory markers in people with T2DM. Method: PRISMA and PICOS frameworks were used for the review. EBSCOhost was used to search for relevant literature in health science research databases, while EMBASE and reference lists were used to access other relevant articles. Results: For systematic review and meta-analysis, 14 and 12 studies, respectively, were included (five from Iran, two each from the USA and India, and one each from the UK, China, Germany, Portugal, and Iraq). All participants had T2DM with ages ranging from ≥30–65 years. The effect of cinnamon on glycaemic control and other parameters did not follow a regular pattern. Effect on HbA1c (nine studies and 605 participants; MD of −0.07 (95% CI, −0.13, −0.01, p = 0.02), postprandial blood glucose (PBG) and BMI showed significant (p < 0.05) reductions. However, cinnamon exhibited no significant (p > 0.05) impact on FBG (MD of −1.73 (95% CI, −3.98, 0.52, p = 0.13), CRP, TNF-α, and IL-6 in people with T2D; neither did the sensitivity test reveal any change in relation to these parameters. Conclusions: Cinnamon or cinnamon extracts/products are significantly effective in diabetes management through reduction in HbA1c, PBG, and BMI. Full article

Background: Osteoporosis is common in transplant recipients, and fracture risk is high. Standard treatment is with anti-resorptive medications. Despite high fracture rates, there are limited data on the use of anabolic bone therapies in transplant recipients. Aim: To evaluate skeletal outcomes after treatment with romosozumab for 12 months in heart and lung transplant recipients. Methods: Retrospective analysis of transplant recipients who completed 12 months of romosozumab treatment at a single centre. Results: Six transplant recipients completed 12 months of romosozumab treatment, commenced after a median of 3 years post transplant (range 2–20). Four patients (66%) were still receiving prednisolone treatment at the time of starting romosozumab. All patients had a history of fracture and had previously received anti-resorptive therapy (4 with zoledronate, 2 with denosumab for >2 years). Following completion of romosozumab treatment, all patients were consolidated with zoledronate or denosumab. Bone mineral density (BMD) was measured prior to and after completion of romosozumab treatment. The median baseline lumbar spine (LS) T-score was −2.3 SD (range −3.1 to +0.9) and total femur T-score was −2.2 SD (range −2.9 to −1.6). Most (5/6) patients experienced an increase in BMD at the LS (median change +7.1%). Most (5/6) patients did not experience clinically significant change in total femur BMD, apart from one patient who experienced a 9% gain. Three patients (50%) experienced subsequent fractures during (1/3) or after completing (2/3) romosozumab treatment. Conclusions: These cases demonstrate severe osteoporosis in transplant recipients. Most patients in our case series had improvement in LS BMD following romosozumab treatment, yet new fractures still occurred during follow-up. The appropriate use of romosozumab in heart and lung transplant patients with osteoporosis requires further study. Full article

Objective: The effect of testosterone on the development of cardiovascular disease (CVD) is of interest due to the higher risk of CVD in men. This study aims to examine the impact of testosterone depletion and supplementation on atherosclerosis progression in normoglycemic and hyperglycemic mouse models. Methods: Male apolipoprotein E-deficient (ApoE^−/−) and hyperglycemic (insulin deficient) ApoE^−/−Ins2^+/Akita mice were fed a standard chow diet and were either castrated or subjected to sham operations at 5 weeks of age. At 8 and 16 weeks of age, subsets of these mice were implanted subcutaneously with a silastic tube containing either 40 µL of dihydrotestosterone (DHT, 25 mg/mL) or sesame oil as a vehicle control. Survival was monitored and all remaining mice were sacrificed at 24 weeks of age. Blood, heart, and aortic samples were collected for analysis. Metabolic parameters were evaluated, and atherosclerotic lesion volumes were measured at the aortic sinus and in en face whole aorta mounts. Results: Castration significantly promoted atherosclerosis in normoglycemic mice, with a 3.0-fold increase (p < 0.05) at the aortic sinus and a 3.5-fold increase (p < 0.05) in en face aortas. However, in hyperglycemic mice, castration attenuated atherosclerosis in en face aortas. Supplementation with exogenous DHT led to increased atherosclerosis in hyperglycemic mice and was associated with significant cardiac-related mortality in 21–24-week-old hyperglycemic mice. Conclusions: In this mouse model, while testosterone/DHT may offer cardioprotective benefits under normoglycemic conditions, it appears to exert substantial harmful effects, such as promoting atherosclerosis and increasing the risk of myocardial infarction, in hyperglycemic conditions. Full article