Exploring new mechanisms of Imeglimin in diabetes treatment: Amelioration of mitochondrial dysfunction.

With the increasing prevalence of type 2 diabetes mellitus (T2DM), it has become critical to identify effective treatment strategies. In recent years, the novel oral hypoglycaemic drug Imeglimin has attracted much attention in the field of diabetes treatment. The mechanisms of its therapeutic action are complex and are not yet fully understood by current research. Current evidence suggests that pancreatic ß-cells, liver, and skeletal muscle are the main organs in which Imeglimin lowers blood glucose levels and that it acts mainly by targeting mitochondrial function, thereby inhibiting hepatic gluconeogenesis, enhancing insulin sensitivity, promoting pancreatic ß-cell function, and regulating energy metabolism. There is growing evidence that the drug also has a potentially volatile role in the treatment of diabetic complications, including metabolic cardiomyopathy, diabetic vasculopathy, and diabetic neuroinflammation. According to available clinical studies, its efficacy and safety profile are more evident than other hypoglycaemic agents, and it has synergistic effects when combined with other antidiabetic drugs, and also has potential in the treatment of T2DM-related complications. This review aims to shed light on the latest research progress in the treatment of T2DM with Imeglimin, thereby providing clinicians and researchers with the latest insights into Imeglimin as a viable option for the treatment of T2DM.

Corrigendum: Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.

[This corrects the article DOI: 10.3389/fendo.2023.1299206.].

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment.

BACKGROUND: Several studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. OBJECTIVE: To determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). METHODS: In this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. RESULTS: The serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. CONCLUSIONS: Our study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

Phosphatidate phosphatase Lipin1 involves in diabetic encephalopathy pathogenesis via regulating synaptic mitochondrial dynamics.

Diabetic encephalopathy (DE) is a common central nervous system complication of diabetes mellitus without effective therapy currently. Recent studies have highlighted synaptic mitochondrial damages as a possible pathological basis for DE, but the underlying mechanisms remain unclear. Our previous work has revealed that phosphatidate phosphatase Lipin1, a critical enzyme involved with phospholipid synthesis, is closely related to the pathogenesis of DE. Here, we demonstrate that Lipin1 is significantly down-regulated in rat hippocampus of DE. Knock-down of Lipin1 within hippocampus of normal rats induces dysregulation of homeostasis in synaptic mitochondrial dynamics with an increase of mitochondrial fission and a decrease of fusion, then causes synaptic mitochondrial dysfunction, synaptic plasticity deficits as well as cognitive impairments, similar to that observed in response to chronic hyperglycemia exposure. In contrast, an up-regulation of Lipin1 within hippocampus in the DE model ameliorates this cascade of dysfunction. We also find that the effect of Lipin1 that regulating mitochondrial dynamics results from maintaining appropriate phospholipid components in the mitochondrial membrane. In conclusion, alterations in hippocampal Lipin1 contribute to hippocampal synaptic mitochondrial dysfunction and cognitive deficits observed in DE. Targeting Lipin1 might be a potential therapeutic strategy for the clinical treatment of DE.

Changes in the central nervous system in diabetic neuropathy.

One of the most common chronic complications arising from diabetes is diabetic peripheral neuropathy. Depending on research statistics, approximately half of the people who have diabetes will suffer from diabetic peripheral neuropathy over time, which manifests as abnormal sensations in the distal extremities, and about 25%-50% of these patients have symptoms of neuralgia, called painful diabetic neuropathy. These patients often exhibit adverse emotional conditions, like anxiety or depression, which can reduce their quality of life. The pathogenesis of diabetic peripheral neuropathy is complex, and although persistent hyperglycemia plays a central role in the development of diabetic peripheral neuropathy, strict glycemic control does not eliminate the risk of diabetic peripheral neuropathy. This suggests the need to understand the role of the central nervous system in the development of diabetic peripheral neuropathy to modulate treatment regimens accordingly. Magnetic resonance imaging not only allows for the noninvasive detection of structural and functional alterations in the central nervous system, but also provides insight into the processing of abnormal information such as pain by the central nervous system, and most importantly, contributes to the development of more effective pain relief protocols. Therefore, this article will focus on the mechanisms and related imaging evidence of central alterations in diabetic peripheral neuropathy, especially in painful diabetic neuropathy.

Lipin2 ameliorates diabetic encephalopathy via suppressing JNK/ERK-mediated NLRP3 inflammasome overactivation.

OBJECTIVES: Diabetic encephalopathy (DE) is a common complication of diabetes in the central nervous system, which can cause cognitive dysfunction in patients. However, its pathophysiological mechanism has not been elucidated, and thus effective prevention and treatment methods are still lacking.Previous studies reported that neuroinflammation involved in the central neuropathy, while lipin2 plays an important role in inflammatory response.Therefore, we aimed to investigate the effects of lipin2 on regulating inflammatory response in the pathogenesis of DE. METHODS: BV2 cells were treated with high glucose and infected with lipin2 overexpression or knockdown virus to observe the cell viability. Then, we constructed a mouse model of DE, and constructed a lipin2 knockdown or overexpression model by injecting lentivirus into the brain with stereotaxis. The expression of lipin2 in inflammatory bodies and related inflammatory factor signaling pathway-related proteins were examined by western blot and quantitative real-time PCR. Morris water maze was used to evaluate the spatial learning and memory of mice. RESULTS: High glucose decreased the expression of lipin2 in BV2 cells, while overexpression of lipin2 in BV2 cells significantly suppressed the inflammatory response and apoptosis induced by high glucose. Meanwhile, the expression of lipin2 was down-regulated in the hippocampus in a DE mice model. Up-regulation of lipin2 in the hippocampus of DE mice inhibited JNK/ERK signaling pathway, reduced NLRP3 inflammasome-mediated inflammatory response, down-regulated IL-1/TNF-α expression, and improved synaptic plasticity and cognitive dysfunction in mice. Conversely, knockdown of lipin2 increased NLRP3 inflammasome overactivation, caused neuronal abnormalities and cognitive impairment in mice. CONCLUSIONS: Lipin2 may play a neuroprotective role in DE by inhibiting JNK/ERK-mediated NLRP3 inflammasome overactivation and subsequent inflammatory responses. It may be a potential therapeutic target for DE therapy.

Research Progress on Lipocalin-2 in Diabetic Encephalopathy.

Diabetic encephalopathy is a central nervous complication of diabetes mellitus which is characterized by cognitive impairment and structural and neurochemical abnormalities, which is easily neglected. Lipocalin-2 (LCN2) is a 25 kDa transporter in the lipocalin family that can transport small molecules, including fatty acids, iron, steroids, and lipopolysaccharides in the circulation. Recently, LCN2 has been found to be a significant regulator of insulin resistance and glucose homeostasis. Numerous studies have shown that LCN2 is connected to central nervous system abnormalities, including neuroinflammation and neurodegeneration, while the latest researches have found that LCN2 is closely related to the development of diabetic encephalopathy. Nevertheless, its precise role in the pathogenesis of diabetic encephalopathy remains to be determined. In this paper, we review recent evidence on the role of LCN2 in diabetic encephalopathy from multiple perspectives in order to decipher the impact of LCN2 in both the aetiology and treatment of diabetic encephalopathy.

Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.

Background: Cognitive Impairment arising from type 2 diabetes mellitus (T2DM) has garnered significant attention in recent times. However, there are few studies on the identification and diagnosis of markers of cognitive impairment. Notably, alterations in the Retinal Nerve Fiber Layer's (RNFL) thickness can potentially serve as an indicative measure of central nervous system changes. Further investigations have indicated that the decline in cognitive function within T2DM patients is intricately linked to persistent systemic inflammation and the accumulation of advanced glycosylation end products. Comprehensive studies are warranted to unveil these complex associations. Objective: This study aims to explore the potential of utilizing the RNFL thickness and serological concentrations of IL-18, irisin, CML, and RAGE as diagnostic indicators for Mild Cognitive Impairment (MCI) among individuals with T2DM. Methods: The thickness of RNFL were determined in all patients and controls using optical coherence tomography (OCT). The serum levels of IL-18, irisin, CML and RAGE were detected by ELISA kit. In addition, Cognitive assessment was performed by the Mini-Mental State Examination (MMSE) and the Montreal Cognitive assessment (MoCA). Results: The average RNFL thickness in the right eye were decreased in T2DM and T2DM combined with MCI (T2DM-MCI) patients and were positively correlated with MoCA and MMSE scores. The serum levels of IL-18, CML and RAGE in T2DM and T2DM-MCI increased significantly (p<0.05) and were negative correlated with MoCA and MMSE scores. The level of irisin in T2DM and T2DM-MCI decreased significantly (p<0.05) and were positively correlated with MoCA and MMSE scores. The area under the ROC curve of T2DM-MCI predicted by the average RNFL thickness in the right eye, CML and RAGE were 0.853, 0.874 and 0.815. The diagnostic efficacy of the combination of average RNFL thickness in the right eye, CML, and RAGE for the diagnosis of T2DM-MCI was 0.969. Conclusion: The average RNFL thickness in the right eye, CML and RAGE have possible diagnostic value in T2DM-MCI patients.

Effectiveness Evaluation of a Primary School-Based Intervention against Heatwaves in China.

BACKGROUND: Evidence of the effectiveness of intervention against extreme heat remains unclear, especially among children, one of the vulnerable populations. This study aimed to evaluate the effectiveness of a primary school-based intervention program against heatwave and climate change in China to provide evidence for development of policies for adaptation to climate change. METHODS: Two primary schools in Dongtai City, Jiangsu Province, China, were randomly selected as intervention and control schools (CTR registration number: ChiCTR2200056005). Health education was conducted at the intervention school to raise students' awareness and capability to respond to extreme heat during May to September in 2017. Knowledge, attitude, and practice (KAP) of students and their parents at both schools were investigated by questionnaire surveys before and after intervention. The changes in KAP scores after intervention were evaluated using multivariable difference-in-difference (DID) analysis, controlling for age, sex, etc. Results: The scores of knowledge, attitude, and practice of students and their parents increased by 19.9% (95%CI: 16.3%, 23.6%) and 22.5% (95%CI: 17.8%, 27.1%); 9.60% (95%CI: 5.35%, 13.9%) and 7.22% (95%CI: 0.96%, 13.5%); and 9.94% (95%CI: 8.26%, 18.3%) and 5.22% (95%CI: 0.73%, 9.71%), respectively, after intervention. The KAP score changes of boys were slightly higher than those of girls. Older students had higher score changes than younger students. For parents, the higher the education level, the greater the score change, and change in scores was greater in females than in males. All the health education activities in the program were significantly correlated with the changes in KAP scores of primary school students after intervention, especially those curricula with interesting activities and experiential learning approaches. CONCLUSIONS: Heat and health education program in primary school was an effective approach to improve cognition and behavior for both students and their parents to better adapt to heatwaves and climate change. The successful experience can be generalized to respond to the increasing extreme weather/climate events in the context of climate change, such as heatwaves, and other emergent occasions or public health education, such as the control and prevention of COVID-19.

Lipin1 Alleviates Autophagy Disorder in Sciatic Nerve and Improves Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes, and its neural mechanisms underlying the pathogenesis remain unclear. Autophagy plays an important role in neurodegenerative diseases and nerve tissue injury. Lipin1 is a phosphatidic acid phosphatase enzyme that converts phosphatidic acid (PA) into diacylglycerol (DAG), a precursor of triacylglycerol and phospholipids which plays an important role in maintaining normal peripheral nerve conduction function. However, whether Lipin1 involved in the pathogenesis of DPN via regulation of autophagy is not elucidated. Here, we show that the Lipin1 expression was downregulated in streptozotocin (STZ)-induced DPN rat model. Interestingly, STZ prevented DAG synthesis, and resulted in autophagic hyperactivity, effects which may increase the apoptosis of Schwann cells and lead to demyelination in sciatic nerve in DPN rats. More importantly, upregulation of lipin1 in the DPN rats ameliorated autophagy disorders and pathological changes of the sciatic nerve, which associated with the increase of the motor nerve conductive velocity (MNCV) in DPN rats. In contrast, knockdown of lipin1 exacerbates neuronal abnormalities and facilitates the genesis of DPN phenotypes in rats. In addition, overexpression of lipin1 in RSC96 cells also significantly decreased the autophagic hyperactivity and apoptosis induced by hyperglycemia. These results suggest that lipin1 may exert neuroprotection within the sciatic nerve anomalies and may serve as a potential therapeutic target for the treatment of DPN.

Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19.

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

Baseline characteristics and changes of biomarkers in disease course predict prognosis of patients with COVID-19.

The outbreak of coronavirus disease (COVID-19) has brought great challenges to the world. The objectives of this study were to describe the baseline characteristics and changes of biomarkers of these COVID-19 patients and identify predictive value of the above markers for patient death. Using patient death as the observational endpoints, clinical data of inpatients in a special ward for COVID-19 in Wuhan, China were retrospectively collected. Univariate and multivariate Cox regression analyses were used to evaluate prognostic value of baseline characteristics and laboratory data changes. This study included clinical data of 75 patients. Age, c-reactive protein (CRP) and interleukin-6 levels were independent predictors of patient death. Survivors were characterized as having declining neutrophil counts, D-dimer, N-terminal pronatriuretic peptide, troponin I (TnI) and c-reactive protein levels, while counts of lymphocyte gradually came back. Non-survivors were characterized with increasing white blood cell counts (WBC) and neutrophil counts. Changes of WBC, TnI and interleukin-6 were also independently associated with patient death. Older age, baseline CRP and IL-6 levels may be used as meaningful predictors to identify patients with poor prognosis. Changes of biomarkers should be closely monitored in the management of patients with COVID-19, while constantly increasing levels of WBC, TnI and interleukin-6 in the disease course also predict patient death.

Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway.

Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.

Atypical juvenile hereditary hemochromatosis onset with positive pancreatic islet autoantibodies diabetes caused by novel mutations in HAMP and overall clinical management.

BACKGROUND: Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death. METHODS: The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype-genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype-phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464). RESULTS: Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic-onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases. CONCLUSION: It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss-of-function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH.

Abnormal liver-related biomarkers in COVID-19 patients and the role of prealbumin.

Background/Aims: We aimed to evaluate the distribution of abnormal liver-related biomarkers in patients with coronavirus disease (COVID-19) and explore the prognostic value of elevated liver enzymes and abnormal liver synthetic capacity with regards to patient mortality. Patients and Methods: This retrospective observational study included 80 laboratory-confirmed COVID-19 cases. Data were collected from the electronic medical record system by a trained team of physicians. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin, and prealbumin levels at admission and on day 7 after admission were collected. The primary outcome of the current study was patient mortality. Results: Abnormal ALT, AST, TB, albumin, and prealbumin levels were observed in 11 (13.8%), 15 (18.8%), 5 (6.3%), 22 (27.5%), and 31 (38.8%) patients, respectively. Male gender correlated with elevated ALT and AST levels (p = 0.027 and 0.036, respectively). Higher levels of AST and lower levels of albumin and prealbumin were associated with patient mortality (p = 0.009, 0.002, and 0.003, respectively). Multivariate Cox regression analysis identified patient age (p = 0.013, HR 1.108) and prealbumin levels (p = 0.015, HR 0.986) as independent predictors for patient mortality. However, changes in liver-related biomarkers were not associated with poor outcome in multivariate analysis (p > 0.05). Conclusions: Abnormalities in albumin and prealbumin levels are common among COVID-19 patients and hypoprealbuminemia independently predicts adverse outcome and should be carefully considered in clinical practice. Moreover, changes in liver-related biomarkers is not a salient feature of COVID-19.

Association between bile acid metabolism and bone mineral density in postmenopausal women.

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (ß-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with ß-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Lipin1 mediates cognitive impairment in fld mice via PKD-ERK pathway.

Lipin1 is important in lipid synthesis because of its phosphatidate phosphatase activity, and it also functions as transcriptional coactivators to regulate the expression of genes involved in lipid metabolism. We found that fld mice exhibit cognitive impairment, and it is related to the DAG-PKD-ERK pathway. We used fld mice to explore the relationship between lipin1 and cognitive function. Our results confirmed the presence of cognitive impairment in the hippocampus of lipin1-deficient mice. As shown in behavioral test, the spatial learning and memory ability of fld mice was much worse than that of wild-type mice. Electron microscopy results showed that the number of synapses in hippocampus of fld mice was significantly reduced. BDNF,SYP, PSD95 were significantly reduced. These results suggest that lipin1 impairs synaptic plasticity. Hence,a deficiency of lipin1 leads to decreased DAG levels and inhibits PKD activation, thereby affecting the phosphorylation of ERK and the CREB.

Association between bile acid metabolism and bone mineral density in postmenopausal women

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.