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Gan LL, Xia C, Zhu X, Gao Y, Wu WC, Li Q, Li L, Dai Z, Yan YM. Predictive value of angiopoietin-like protein 8 in metabolic dysfunction-associated fatty liver disease and its progression: A case-control study. World J Diabetes 2024; 15:418-428. [PMID: 38591072 PMCID: PMC10999044 DOI: 10.4239/wjd.v15.i3.418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/05/2024] [Accepted: 02/18/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rapidly increasing, currently affecting approximately 25% of the global population. Liver fibrosis represents a crucial stage in the development of MAFLD, with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma. Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers. However, imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints. Consequently, it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis. AIM To investigate the predictive value of angiopoietin-like protein 8 (ANGPTL8) in MAFLD and its progression. METHODS We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department, Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology, during September 2021-July 2022. Using abdominal ultrasonography and MAFLD diagnostic criteria, among the 160 patients, 80 patients (50%) were diagnosed with MAFLD. The MAFLD group was divided into the liver fibrosis group (n = 23) and non-liver fibrosis group (n = 57) by using a cut-off fibrosis-4 index ≥ 1.45. Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression. Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression. RESULTS Compared with non-MAFLD patients, MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose (TyG) index (both P < 0.05). Serum ANGPTL8 (r = 0.576, P < 0.001) and TyG index (r = 0.473, P < 0.001) were positively correlated with MAFLD. Serum ANGPTL8 was a risk factor for MAFLD [odds ratio (OR): 1.123, 95% confidence interval (CI): 1.066-1.184, P < 0.001). Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD [area under the curve (AUC): 0.832 and 0.886, respectively; both P < 0.05]. Compared with MAFLD patients without fibrosis, those with fibrosis had higher serum ANGPTL8 and TyG index (both P < 0.05), and both parameters were positively correlated with MAFLD-associated fibrosis. Elevated serum ANGPTL8 (OR: 1.093, 95%CI: 1.044-1.144, P < 0.001) and TyG index (OR: 2.383, 95%CI: 1.199-4.736, P < 0.013) were risk factors for MAFLD-associated fibrosis. Serum ANGPTL8 and ANGPTL8 + TyG index predicted MAFLD-associated fibrosis (AUC: 0.812 and 0.835, respectively; both P < 0.05). CONCLUSION The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD. They can serve as predictors for the risk of MAFLD and liver fibrosis, with the ANGPTL8 + TyG index potentially exhibiting even higher predictive value.
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Affiliation(s)
- Lu-Lu Gan
- Medical College, Wuhan University of Science and Technology, Wuhan 430071, Hubei Province, China
- Department of Endocrinology, Xiaogan Hospital Affiliated with Wuhan University of Science and Technology, The Central Hospital of Xiaogan, Xiaogan 432000, Hubei Province, China
| | - Can Xia
- Medical College, Wuhan University of Science and Technology, Wuhan 430071, Hubei Province, China
| | - Xuan Zhu
- Medical College, Wuhan University of Science and Technology, Wuhan 430071, Hubei Province, China
| | - Yue Gao
- Medical College, Wuhan University of Science and Technology, Wuhan 430071, Hubei Province, China
| | - Wen-Chang Wu
- Medical College, Wuhan University of Science and Technology, Wuhan 430071, Hubei Province, China
| | - Qi Li
- Department of Endocrinology, Xiaogan Hospital Affiliated with Wuhan University of Science and Technology, The Central Hospital of Xiaogan, Xiaogan 432000, Hubei Province, China
| | - Ling Li
- Department of Endocrinology, Xiaogan Hospital Affiliated with Wuhan University of Science and Technology, The Central Hospital of Xiaogan, Xiaogan 432000, Hubei Province, China
| | - Zhe Dai
- Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yi-Min Yan
- Medical College, Wuhan University of Science and Technology, Wuhan 430071, Hubei Province, China
- Department of Endocrinology, Xiaogan Hospital Affiliated with Wuhan University of Science and Technology, The Central Hospital of Xiaogan, Xiaogan 432000, Hubei Province, China
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Ye H, Zong Q, Zou H, Zhang R. Emerging insights into the roles of ANGPTL8 beyond glucose and lipid metabolism. Front Physiol 2023; 14:1275485. [PMID: 38107478 PMCID: PMC10722441 DOI: 10.3389/fphys.2023.1275485] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 11/15/2023] [Indexed: 12/19/2023] Open
Abstract
Angiopoietin-like protein 8 (ANGPTL8) is a secreted protein predominantly expressed in liver and adipose tissue. ANGPTL8 modulates the clearance of triglycerides (TGs) by suppressing the activity of lipoprotein lipase (LPL) within the plasma. Previous studies found that circulating ANGPTL8 levels were significantly increased in metabolic disorder-related diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Whether ANGPTL8 has a direct pathogenic role in these diseases remains to be determined. In this review, we summarize the emerging roles of ANGPTL8 in the regulation of inflammation, tumours, circulatory system-related diseases, and ectopic lipid deposition, which may provide new insights into the diverse functions of ANGPTL8 in various diseases beyond its well-established functions in glucose and lipid metabolism.
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Affiliation(s)
- Huimin Ye
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Qunchuan Zong
- Department of Traumatology and Orthopaedics, The Affiliated Hospital of Qinghai University, Xining, China
| | - Huajie Zou
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Ruixia Zhang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
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Arikan FB, Ulas M, Ustundag Y, Boyunaga H, Badem ND. Investigation of the relationship between betatrophin and certain key enzymes involved in carbohydrate and lipid metabolism in insulin-resistant mice. Horm Mol Biol Clin Investig 2023; 44:311-320. [PMID: 36869875 DOI: 10.1515/hmbci-2022-0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 02/08/2023] [Indexed: 03/05/2023]
Abstract
OBJECTIVES The present study sought to examine the relationship of betatrophin with certain key enzymes, namely lactate dehydrogenase-5 (LDH5), citrate synthase (CS), and acetyl-CoA carboxylase-1 (ACC1), in insulin-resistant mice. METHODS Eight-week-old male C57BL6/J mice were used in this study (experimental group n=10 and control group n=10). S961 was administered using an osmotic pump to induce insulin resistance in the mice. The betatrophin, LDH5, CS, and ACC1 expression levels were determined from the livers of the mice using the real-time polymerase chain reaction (RT-PCR) method. Moreover, biochemical parameters such as the serum betatrophin, fasting glucose, insulin, triglyceride, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels were analyzed. RESULTS The betatrophin expression and serum betatrophin (p=0.000), fasting glucose, insulin, triglyceride (p≤0.001), and total cholesterol (p=0.013) levels were increased in the experimental group. In addition, the CS gene expression level was statistically significantly decreased in the experimental group (p=0.01). Although strong correlation was found between the expression and serum betatrophin and triglyceride levels, no correlation was found between the betatrophin gene expression and the LDH5, ACC1, and CS gene expression levels. CONCLUSIONS The betatrophin level appears to play an important role in the regulation of triglyceride metabolism, while insulin resistance increases both the betatrophin gene expression and serum levels and decreases the CS expression level. The findings suggest that betatrophin may not regulate carbohydrate metabolism through CS and LDH5 or lipid metabolism directly through the ACC1 enzyme.
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Affiliation(s)
- Funda Bulut Arikan
- Faculty of Medicine, Department of Physiology, Kırıkkale University, Kırıkkale, Türkiye
| | - Mustafa Ulas
- Faculty of Medicine, Department of Physiology, Fırat University, Elazığ, Türkiye
| | - Yasemin Ustundag
- Faculty of Veterinary, Department of Anatomy, Dokuz Eylul University, Izmir, Türkiye
| | - Hakan Boyunaga
- Faculty of Medicine, Medical Biochemistry Department, Medipol University, Ankara, Türkiye
| | - Nermin Dindar Badem
- Department of Medical Biochemistry, Health Sciences University, Gülhane Training and Research Hospital, Ankara, Türkiye
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Mohammedsaeed W, Ahmed A, Alharbi N, Aljohani A, Alruwaithi R, Alharbi R, Alahmadi S. Evaluation of Adiponectin and ANGPTL8 in Women With Metabolic Syndrome in the Madinah Region of Saudi Arabia. Cureus 2023; 15:e44219. [PMID: 37767256 PMCID: PMC10522362 DOI: 10.7759/cureus.44219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2023] [Indexed: 09/29/2023] Open
Abstract
OBJECTIVE "Metabolic syndrome" (MetS) is a set of abnormalities that may be risk factors for cardiovascular disease (CVD) and diabetes. The current study sought to (1) determine MetS prevalence and (2) examine Adiponectin and ANGPTL8 levels in connection to MetS components and CVDs and diabetes risk in females with MetS. METHODS A total of 350, 20-35-year-old Saudi females were studied. Waist circumference (WC), body mass index (BMI), glucose, HbA1c, insulin, lipid profiles, and blood pressure (BP) were examined for MetS. ANGPTL8 and Adiponectin were also measured. RESULTS The patients were classified into two groups, namely MetS and non-MetS, according to the criteria established by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). We examined biomarker and anthropometric results between these groups. One hundred forty-four of 350 female participants (41.2%) had MetS, with a mean age of 30.5 years. Fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), ANGPTL8, adiponectin, and insulin resistance (IR) were statistically significant differences observed between the two groups. BP, BMI, WC, and Atherogenic Index of Plasma (AIP) all changed significantly (P ≤0.05). Correlation studies linked MetS components to higher ANGPTL-8 and reduced adiponectin. The levels of ANGPTL8 were shown to be influenced by the increase in FBG, TG, BP, IR, and AIP (P < 0.05). Factors such as FBG, BMI, WC, and IR have been found to have an inverse relationship with adiponectin levels. CONCLUSION 41.2% out of 350 Saudi females at Taibah University in the Madinah region had MetS, medium CVD risk, and slightly elevated BMI, TG, WC, and BP. To lower their risk of CVD and diabetes later in life, overweight young women should be evaluated for MetS. FBG and TG were substantially associated with ANGPTL8 while reducing adiponectin was associated with elevated TG and BP. Our findings may lead to ANGPTL8 and adiponectin's possible predictive function for CVD in early MetS in females.
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Affiliation(s)
- Walaa Mohammedsaeed
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Ahmed Ahmed
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Nada Alharbi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Amjaad Aljohani
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Razan Alruwaithi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Reem Alharbi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
| | - Shatha Alahmadi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Taibah University, Madinah, SAU
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Güngör Kobat S, Gül FC, Çelik F, Liman Uzun S, Kobat MA, Akkoç RF, Aydın S. Plasma and aqueous levels of subfatin, preptin and betatrophin in patients with diabetic retinopathy. BMC Ophthalmol 2023; 23:312. [PMID: 37434133 DOI: 10.1186/s12886-023-03075-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 07/09/2023] [Indexed: 07/13/2023] Open
Abstract
AIM To examine subfatin, preptin and betatrophin levels in plasma and aqueous in patients with diabetes mellitus (DM) (with and without retinopathy). MATERIAL AND METHOD Sixty patients, who were similar in terms of age and gender, and were scheduled for operation due to cataract, were included in the study. The patients were divided into three groups as Group C (20 weeks without diabetes and comorbidity), Group DM (20 patients with DM but no retinopathy) and Group DR (20 patients with diabetic retinopathy). The preoperative body mass index (BMI), fasting plasma glucose, HbA1c, lipid profile levels of all patients in the groups were examined. Blood samples were also taken for plasma subfatin, preptin and betatrophin levels. At the beginning of the cataract surgery, 0.1 ml of aqueous fluid was taken from the anterior chamber. Plasma and aqueous subfatin, preptin and betatrophin levels were analyzed by ELISA (enzyme-linked immunosorbent assays) method. RESULTS In our study results, there was a significant difference in BMI, fasting plasma glucose and hemoglobin A1c levels (p < 0.05 for all parameters). Plasma and aqueous subfatin levels were higher in Group DR compared to Group C (p < 0.001, p = 0.036, respectively). Plasma and aqueous preptin levels were higher in group DR and group DM than in group C (p = 0.001, p = 0.002, p < 0.001, p = 0.001, respectively). Plasma and aqueous betatrophin levels were higher in Group DR compared to group C (p = 0.001, p = 0.010, respectively). CONCLUSION Subfatin, preptin and betatrophin molecules may have an important role in the pathogenesis of diabetic retinopathy.
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Affiliation(s)
| | | | - Fatih Çelik
- Department of Ophthalmology, Elazıg Health Science University, Elazıg, Turkey
| | - Seda Liman Uzun
- Department of Ophthalmology, Elazıg Health Science University, Elazıg, Turkey
| | | | | | - Süleyman Aydın
- Department of Biochemistry, Firat University, Elazıg, Turkey
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Susanto H, Sugiharto, Taufiq A, Pranoto A, Dwi Trijoyo Purnomo J. Dynamic alteration of plasma levels of betatrophin in younger female onset obesity post acute moderate-intensity exercise training. Saudi J Biol Sci 2023; 30:103546. [PMID: 36624736 PMCID: PMC9823226 DOI: 10.1016/j.sjbs.2022.103546] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 11/19/2022] [Accepted: 12/17/2022] [Indexed: 12/25/2022] Open
Abstract
Obesity is a global metabolic disease anchored by a lack of physical activity lipid disturbances. Hitherto, betatrophin is a potential liver-derived hormone that regulates lipid metabolism. A total of 26 selected onset obese individuals (BMI range ± 28-31) were enrolled in this study and given moderate-intensity exercise. Importantly, our data show that acute moderate-intensity interval exercise (MIIE) and acute moderate-intensity continue to exercise (MICE) for 40 min significantly decrease the plasma level of full-length betatrophin respectively (174.18 ± 48.19 ng/mL; 182.31 ± 52.69 ng/mL), compared to the placebo (283.97 ± 32.23 ng/mL) post 10 min and 6 h exercise treatment (p ≤ 0.05). The plasma level of betatrophin was significantly and negatively correlated with BMI (r = - 0.412, p = 0.037), fasting blood glucose (r = - 0.390, p = 0.049), and positively correlated with VO2max (r = 0.456, p = 0.019). In addition, the linear and ordinal logistic regression analysis shows that betatrophin, is a potential predictor for BMI [estimate value = 0.995, p = 0.037 and OR (95 % CI) = 0.992 (0.0984-1.00), p = 0,048]. In summary, our data demonstrate that the circulating levels of betatrophin were decreased after acute moderate-intensity exercise training.
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Affiliation(s)
- Hendra Susanto
- Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Malang, East Java 65145, Indonesia,Corresponding author at: Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Semarang No. 5 Street, Malang, East Java 65145, Indonesia.
| | - Sugiharto
- Department of Sports Science, Faculty of Sports Science, Universitas Negeri Malang, Malang, East Java 65145, Indonesia
| | - Ahmad Taufiq
- Department of Physics, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Malang, East Java 65145, Indonesia
| | - Adi Pranoto
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java 60132, Indonesia
| | - Jerry Dwi Trijoyo Purnomo
- Department of Statistics, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Surabaya, East Java 60117, Indonesia
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Betatrophin and Insulin Resistance. Metabolites 2022; 12:metabo12100925. [PMID: 36295827 PMCID: PMC9610572 DOI: 10.3390/metabo12100925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/09/2022] [Accepted: 09/24/2022] [Indexed: 11/18/2022] Open
Abstract
Betatrophin (angiopoietin-like protein 8 (ANGPTL8)) is a hormone that was recently discovered in the human liver. Multiple homologous sequences have been detected in mammalian liver, white adipose, and brown adipose tissues. Betatrophin is crucial for the development of type 2 diabetes (T2D), insulin resistance, and lipid metabolism. Similar to the intake of insulin, thyroid hormones, irisin, and calories, betatrophin expression in the organism is usually attributed to energy consumption or heat generation. It can mediate the activity of lipoprotein lipase (LPL), which is the key enzyme of lipoprotein lipolysis. Due to its association with metabolic markers and the roles of glucose and lipid, the physiological function of betatrophin in glucose homeostasis and lipid metabolism can be more comprehensively understood. Betatrophin was also shown to facilitate pancreatic β-cell proliferation in a mouse model of insulin resistance. There are also reports that demonstrate that betatrophin regulates triglycerides (TGs) in the liver. Therefore, the process of regulating the physiological function by betatrophin is complicated, and its exact biological significance remains elusive. This study provides a comprehensive review of the current research, and it discusses the possible physiological functions of betatrophin, and specifically the mechanism of betatrophin in regulating blood glucose and blood lipids.
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ANGPTL8 is a negative regulator in pathological cardiac hypertrophy. Cell Death Dis 2022; 13:621. [PMID: 35851270 PMCID: PMC9293964 DOI: 10.1038/s41419-022-05029-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 06/09/2022] [Accepted: 06/16/2022] [Indexed: 01/21/2023]
Abstract
Pathological cardiac hypertrophy is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the role of angiopoietin-like protein 8 (ANGPTL8) in pathological cardiac hypertrophy. We found that serum ANGPTL8 levels were significantly increased in hypertensive patients with cardiac hypertrophy and in mice with cardiac hypertrophy induced by Ang II or TAC. Furthermore, the secretion of ANGPTL8 from the liver was increased during hypertrophic processes, which were triggered by Ang II. In the Ang II- and transverse aortic constriction (TAC)-induced mouse cardiac hypertrophy model, ANGPTL8 deficiency remarkably accelerated cardiac hypertrophy and fibrosis with deteriorating cardiac dysfunction. Accordingly, both recombinant human full-length ANGPTL8 (rANGPTL8) protein and ANGPTL8 overexpression significantly mitigated Ang II-induced cell enlargement in primary neonatal rat cardiomyocytes (NRCMs) and H9c2 cells. Mechanistically, the antihypertrophic effects of ANGPTL8 depended on inhibiting Akt and GSK-3β activation, and the Akt activator SC-79 abolished the antihypertrophic effects of rANGPTL8 in vitro. Moreover, we demonstrated that ANGPTL8 directly bound to the paired Ig-like receptor PIRB (LILRB3) by RNA-seq and immunoprecipitation-mass screening. Remarkably, the antihypertrophic effects of ANGPTL8 were largely blocked by anti-LILRB3 and siRNA-LILRB3. Our study indicated that ANGPTL8 served as a novel negative regulator of pathological cardiac hypertrophy by binding to LILRB3 (PIRB) and inhibiting Akt/GSK3β activation, suggesting that ANGPTL8 may provide synergistic effects in combination with AT1 blockers and become a therapeutic target for cardiac hypertrophy and heart failure.
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Rejeki PS, Baskara PG, Herawati L, Pranoto A, Setiawan HK, Lesmana R, Halim S. Moderate-intensity exercise decreases the circulating level of betatrophin and its correlation among markers of obesity in women. J Basic Clin Physiol Pharmacol 2022; 33:769-777. [PMID: 35286051 DOI: 10.1515/jbcpp-2021-0393] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 02/15/2022] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Positive energy homeostasis due to overnutrition and a sedentary lifestyle triggers obesity. Obesity has a close relationship with elevated levels of betatrophin and may increase the risk of developing metabolic syndrome. Therefore, lifestyle modification through a nonpharmacological approach based on physical exercise is the right strategy in lowering betatrophin levels. This study aimed to analyze the effect of moderate-intensity interval and continuous exercises on decreased betatrophin levels and the association between betatrophin levels and obesity markers in women. METHODS A total of 30 women aged 20-24 years old were randomly divided into three groups. Measurement of betatrophin levels using Enzyme-Linked Immunosorbent Assay (ELISA). Data analysis techniques used were one-way ANOVA and parametric linear correlation. RESULTS The results showed that the average levels of betatrophin pre-exercise were 200.40 ± 11.03 pg/mL at CON, 203.07 ± 42.48 pg/mL at MIE, 196.62 ± 21.29 pg/mL at MCE, and p=0.978. Average levels of betatrophin post-exercise were 226.65 ± 18.96 pg/mL at CON, 109.31 ± 11.23 pg/mL at MIE, 52.38 ± 8.18 pg/mL at MCE, and p=0.000. Pre-exercise betatrophin levels were positively correlated with age, BMI, FM, WHR, FBG, and PBF (p≤0.001). CONCLUSIONS Our study showed that betatrophin levels are decreased by 10 min post-MIE and post-MCE. However, moderate-intensity continuous exercise is more effective in lowering betatrophin levels than moderate-intensity interval exercise. In addition, pre-exercise betatrophin levels also have a positive correlation with obesity markers.
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Affiliation(s)
- Purwo Sri Rejeki
- Department of Medical Physiology and Biochemistry, Physiology Division, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Pradika Gita Baskara
- Sport Health Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Lilik Herawati
- Department of Medical Physiology and Biochemistry, Physiology Division, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Adi Pranoto
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Hayuris Kinandita Setiawan
- Department of Medical Physiology and Biochemistry, Physiology Division, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Ronny Lesmana
- Department of Biomedical Science, Physiology Division, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Shariff Halim
- Clinical Research Centre, Management and Science University, Shah Alam, Malaysia
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Relationship between Serum Angiopoietin-like Proteins 3 and 8 and Atherogenic Lipid Biomarkers in Non-Diabetic Adults Depends on Gender and Obesity. Nutrients 2021; 13:nu13124339. [PMID: 34959891 PMCID: PMC8709017 DOI: 10.3390/nu13124339] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/25/2021] [Accepted: 11/29/2021] [Indexed: 11/16/2022] Open
Abstract
Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25-74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.
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Abstract
ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.
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Affiliation(s)
- Chang Guo
- Department of Nephrology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, People's Republic of China
| | - Chenxi Wang
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, People's Republic of China
| | - Xia Deng
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, People's Republic of China
| | - Jianqiang He
- Department of Nephrology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, People's Republic of China
| | - Ling Yang
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, People's Republic of China
| | - Guoyue Yuan
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu, People's Republic of China
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Kucukoglu O, Sowa JP, Mazzolini GD, Syn WK, Canbay A. Hepatokines and adipokines in NASH-related hepatocellular carcinoma. J Hepatol 2021; 74:442-457. [PMID: 33161047 DOI: 10.1016/j.jhep.2020.10.030] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 10/26/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022]
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing in industrialised societies; this is likely secondary to the increasing burden of non-alcoholic fatty liver disease (NAFLD), its progressive form non-alcoholic steatohepatitis (NASH), and the metabolic syndrome. Cumulative studies suggest that NAFLD-related HCC may also develop in non-cirrhotic livers. However, prognosis and survival do not differ between NAFLD- or virus-associated HCC. Thus, research has increasingly focused on NAFLD-related risk factors to better understand the biology of hepatocarcinogenesis and to develop new diagnostic, preventive, and therapeutic strategies. One important aspect thereof is the role of hepatokines and adipokines in NAFLD/NASH-related HCC. In this review, we compile current data supporting the use of hepatokines and adipokines as potential markers of disease progression in NAFLD or as early markers of NAFLD-related HCC. While much work must be done to elucidate the mechanisms and interactions underlying alterations to hepatokines and adipokines, current data support the possible utility of these factors - in particular, angiopoietin-like proteins, fibroblast growth factors, and apelin - for detection or even as therapeutic targets in NAFLD-related HCC.
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Affiliation(s)
- Ozlem Kucukoglu
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Jan-Peter Sowa
- Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany
| | - Guillermo Daniel Mazzolini
- Laboratory of Gene Therapy, Instituto de Investigaciones en Medicina Traslacional, CONICET-Universidad Austral, Buenos Aires 999071, Argentina; Liver Unit, Hospital Universitario Austral, Universidad Austral, Argentina
| | - Wing-Kin Syn
- Section of Gastroenterology, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA; Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, 48940 Leioa, Vizcaya, Spain
| | - Ali Canbay
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
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Wang X, Wang H, Li J, Gao X, Han Y, Teng W, Shan Z, Lai Y. Combined Effects of Dyslipidemia and High Adiposity on the Estimated Glomerular Filtration Rate in a Middle-Aged Chinese Population. Diabetes Metab Syndr Obes 2021; 14:4513-4522. [PMID: 34785920 PMCID: PMC8590978 DOI: 10.2147/dmso.s337190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/04/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Some studies have reported that chronic kidney disease (CKD) or the estimated glomerular filtration rate (eGFR) is significantly associated with metabolic abnormalities. METHODS Six hundred forty-six community residents aged 45-60 years without overt renal dysfunction were recruited in this cross-sectional study. eGFR was estimated by serum creatinine measurement. The visceral fat area (VFA) and subcutaneous fat area (SFA) were assessed by magnetic resonance imaging (MRI). The body mass index (BMI) and waist-hip ratio (WHR) were also evaluated. Additionally, we tested the subjects' blood lipid levels to diagnose dyslipidemia. RESULTS Compared with the subjects with neither dyslipidemia nor obesity, men with both dyslipidemia and high obesity indices, such as BMI, WHR and VFA, showed a significantly lower mean eGFR; women with dyslipidemia with high WHR, VFA or SFA also showed a significantly lower mean eGFR. Although an independent association between the metabolic variables and eGFR was not found except for BMI, some of the combined effects of each variable were related to eGFR decline. Comorbidity of dyslipidemia and high WHR was significant risk factor for eGFR reduction (β -8.805, SD 4.116, p < 0.05). Additionally, comorbidity of dyslipidemia and high obesity indices such as BMI (β -12.942, SD 5.268, p < 0.05) and VFA (β -7.069, SD 3.394, p < 0.05) were significant risk factors for eGFR reduction in men. CONCLUSION The combined effect of dyslipidemia and high obesity indices is significantly related to the decline in eGFR. The association is more profound in men.
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Affiliation(s)
- Xichang Wang
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Haoyu Wang
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Jiashu Li
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Xiaotong Gao
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Yutong Han
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Weiping Teng
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Zhongyan Shan
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Yaxin Lai
- Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
- Correspondence: Yaxin Lai Department of Endocrinology and Metabolism and the Institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, 110001, People’s Republic of ChinaTel +86-13804048045 Email
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14
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Sadeghipour HR, Yeganeh G, Zar A, Salesi M, Akbarzadeh S, Bernardi M. The effect of 4-week endurance training on serum levels of irisin and betatrophin in streptozotocin- induced diabetic rats. Arch Physiol Biochem 2020; 129:575-581. [PMID: 33270481 DOI: 10.1080/13813455.2020.1849310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Betatrophin known as pancreatic β-cell proliferation marker is secreted as a result of the muscle irisin's expression induced by exercise. The present study aimed to investigate the effect of endurance training on serum levels of irisin and betatrophin in diabetic rats. Twenty-four Wistar rats were randomly divided into three groups of (1) healthy control group (H-CG), (2) diabetic control group (D-CG), and diabetic group submitted to endurance training (D-ETG). The D-ETG performed endurance exercise (4 week/5 days) on the rodent treadmill. For data analysis we used one-way ANOVA, Scheffe test and Pearson correlation coefficient. Irisin (p = .04) and betatrophin (p = .005) levels were significantly decreased in the D-CG. Endurance exercise only increased serum levels of irisin significantly (p = .03). There was a significant correlation was shown between serum betatrophin and beta-cell function (p = .03). It appears that a specific exercise training can increase irisin hormone, with possible impact on betatrophin expression in diabetic individuals.
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Affiliation(s)
- Hamid Reza Sadeghipour
- Department of Sport Science, School of Literature and Humanities, Persian Gulf University, Boushehr, Iran
| | - Golan Yeganeh
- Department of Biochemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Abdossaleh Zar
- Department of Sport Science, School of Literature and Humanities, Persian Gulf University, Boushehr, Iran
| | - Mohsen Salesi
- Department of Sport Science, School of Psychology and Education, Shiraz University, Shiraz, Iran
| | - Samad Akbarzadeh
- Department of Biochemistry, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Marco Bernardi
- School of Specialty in Sports Medicine and Physical Exercise; Department of Physiology and Pharmacology, "V. Erspamer"; "Sapienza", University of Rome, Rome, Italy
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Cheng Y, Li Y, Xiong Y, Zou Y, Chen S, Zhang W, Liu C, Shi Y. Liver-specific knockdown of ANGPTL8 alters the structure of the gut microbiota in mice. ANN MICROBIOL 2020. [DOI: 10.1186/s13213-020-01599-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Purpose
To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota.
Methods
We constructed mice with liver-specific ANGPTL8 knockdown by using an adeno-associated virus serotype 8 (AAV8) system harbouring an ANGPTL8 shRNA. We analysed the structure and function of the gut microbiome through pyrosequencing and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction.
Results
Compared with controls, ANGPTL8 shRNA reduced the Simpson index and Shannon index (p < 0.01) of the gut microbiota in mice. At the phylum level, the sh-ANGPTL8 group showed a healthier gut microbiota composition than controls (Bacteroidetes: controls 67.52%, sh-ANGPTL8 80.75%; Firmicutes: controls 10.96%, sh-ANGPTL8 8.58%; Proteobacteria: controls 9.29%, sh-ANGPTL8 0.98%; F/B ratio: controls 0.16, sh-ANGPTL8 0.11). PCoA and UPGMA analysis revealed a significant difference in microbiota composition, while KEGG analysis revealed a significant difference in microbiota function between controls and the sh-ANGPTL8 group.
Conclusion
Our results revealed that inhibition of ANGPTL8 signalling altered the structure of the gut microbiome, which might further affect the metabolism of mice. We have thus identified ANGPTL8 as a novel hepatogenic hormone potentially involving the liver-gut axis and regulating the structure of the gut microbiota.
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Changes in serum levels of angiopoietin-like protein-8 and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 after ezetimibe therapy in patients with dyslipidemia. Clin Chim Acta 2020; 510:675-680. [PMID: 32858055 DOI: 10.1016/j.cca.2020.08.030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/26/2020] [Accepted: 08/21/2020] [Indexed: 01/09/2023]
Abstract
Changes in serum levels of angiopoietin-like protein-8 (ANGPTL8) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) in patients with dyslipidemia after ezetimibe therapy remain to be elucidated. Thirty-eight patients who initially received ezetimibe and were followed for 16 weeks were enrolled. Various parameters were investigated before and after 16 weeks of ezetimibe treatment in all patients. In addition, the patients were also divided into metabolic syndrome (MetS) (n = 22) and Non-MetS (n = 16) groups, and various parameters were compared between these groups. ANGPTL8 was significantly positively correlated with triglyceride (TG) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) before treatment in all patients and in the MetS group. After treatment, TC and LDL-C were significantly decreased in all patients, and in both the MetS and Non-MetS groups, whereas there were no changes in TG or HDL-C. Serum levels of remnant-like particle cholesterol (RLP-C) significantly decreased in all patients and in the MetS group. The ANGPTL8 level before treatment was significantly positively associated with TG and negatively correlated with HDL-C in all patients and in the MetS group. ANGPTL8 and GPIHBP1were significantly decreased after treatment in all patients. GPIHBP1 was also significantly decreased after treatment in both groups. In conclusion, this is the first report to support the possibility of a new effect of ezetimibe therapy. Ezetimibe significantly decreased the serum level of LDL-C, but not TG or HDL-C, while reducing ANGPTL8 and GPIHBP1 in all patients with dyslipidemia. In addition, ezetimibe significantly decreased RLP-C levels in the MetS group.
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Moderate-Intensity Exercise and Musical Co-Treatment Decreased the Circulating Level of Betatrophin. Int J Endocrinol 2020. [DOI: 10.1155/2020/3098261] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Introduction. In general, the significant contribution of lack of physical activity is strongly correlated with lipid metabolism and metabolic disorder. Hitherto, betatrophin is a potential hormone that regulates the lipid profile in the body circulation-associated triglyceride level. This study was designed to evaluate the alteration of betatrophin levels in subject-onset hypertriglyceridemia with exercise intervention co-treated with music. Materials and Methods. A total of 60 nonprofessional athletes were enrolled in this study and given moderate-intensity exercise (MIE) combined with middle rhythm musical co-treatment. The ELISA method was applied to quantify the serum level of betatrophin in all samples. The statistical analysis was performed by applying the Kolmogorov–Smirnov normality test, one-way ANOVA, and parametric linear correlation and regression. Results. Interestingly, our data show that MIE decreased the circulating level of betatrophin combined with music (12.47 ± 0.40 ng/mL) compared with that without musical co-treatment (20.81 ± 1.16 ng/mL) and high-intensity exercise (26.91 ± 2.23 ng/mL). The plasma level of betatrophin was positively correlated with triglycerides (r = 0.316, p≤0.05), systolic blood pressure (r = 0.428, p≤0.01), HDL (r = 0.366, p≤0.05), energy expenditure (r = 0.586, p≤0.001), PGC-1α (r = 0.573, p≤0.001), and irisin (r = 0.863, p≤0.001). By contrast, the plasma level of betatrophin was negatively associated with age (r = −0.298, p≤0.05) and LDL cholesterol (r = −0.372, p≤0.05). Importantly, betatrophin is a significant predictor for energy expenditure (p≤0.001) and plasma triglyceride levels (p≤0.05). Conclusions. Our data demonstrate that betatrophin levels decreased the post-MIE and musical therapeutical combination. Therefore, betatrophin may provide a benefit as the potential biomarker of physiological performance-associated physical training.
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Holmannova D, Borska L, Andrys C, Borsky P, Kremlacek J, Hamakova K, Rehacek V, Malkova A, Svadlakova T, Palicka V, Krejsek J, Fiala Z. The Impact of Psoriasis and Metabolic Syndrome on the Systemic Inflammation and Oxidative Damage to Nucleic Acids. J Immunol Res 2020; 2020:7352637. [PMID: 32537470 PMCID: PMC7256681 DOI: 10.1155/2020/7352637] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 04/14/2020] [Accepted: 04/27/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Psoriasis is a chronic systemic inflammatory disease associated with a wide range of comorbidities, including metabolic syndrome (MetS). Serum calprotectin, ANGPTL8, and oxidative damage to nucleic acids might be associated with both diseases. The presented study describes the influence of psoriasis and MetS on the serum levels of markers of systemic inflammation (calprotectin and ANGPTL8) and markers of oxidative damage to nucleic acids. The applicability of serum levels of calprotectin and ANGPTL8 for monitoring of the activity of psoriasis (diagnostic markers) is also evaluated. METHODS Clinical examination (PASI score, MetS), enzyme-linked immunosorbent assay (ELISA), and Enzyme Immunoassay (EIA). Serum calprotectin, ANGPTL8, 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine. Results and Conclusions. The psoriasis significantly increased the serum level of calprotectin and the serum level of oxidative damage to nucleic acids, however not the serum level of ANGPTL8. The presence of MetS did not significantly affect the serum levels of calprotectin, ANGPTL8, and oxidative damage to nucleic acids in either psoriasis patients or controls. It seems that the serum level of calprotectin (but not the serum level of ANGPTL8) could be used as a biomarker for monitoring the activity of psoriasis.
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Affiliation(s)
- Drahomira Holmannova
- Institute of Hygiene and Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Lenka Borska
- Institute of Pathological Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Ctirad Andrys
- Institute of Clinical Immunology and Allergology, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Pavel Borsky
- Institute of Hygiene and Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
- Institute of Pathological Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Jan Kremlacek
- Institute of Pathological Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Kvetoslava Hamakova
- Clinic of Dermatology and Venereology, University Hospital Hradec Kralove, Czech Republic
| | - Vit Rehacek
- Transfusion Center, University Hospital, Hradec Kralove 500 03, Czech Republic
| | - Andrea Malkova
- Institute of Hygiene and Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Tereza Svadlakova
- Institute of Hygiene and Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
- Institute of Clinical Immunology and Allergology, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Vladimir Palicka
- Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Jan Krejsek
- Institute of Clinical Immunology and Allergology, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Zdenek Fiala
- Institute of Hygiene and Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
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Association of ANGPTL8 (Betatrophin) Gene Variants with Components of Metabolic Syndrome in Arab Adults. Sci Rep 2020; 10:6764. [PMID: 32317770 PMCID: PMC7174409 DOI: 10.1038/s41598-020-63850-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 03/31/2020] [Indexed: 12/21/2022] Open
Abstract
Angiopoietin-like protein 8 (ANGPTL8) has a role in lipid metabolism, beta-cell proliferation and diabetes progression, however, the association between different variants in the ANGPTL8 gene and metabolic syndrome (MetS) components has not been studied widely especially in Arab ethnic groups. In this study, the associations of ANGPTL8 variants on MetS risk in Saudi Arab adults were investigated. A total of 905 unrelated Saudi adults (580 healthy controls and 325 MetS) were included. MetS was screened based on the International Diabetes Federation (IDF) criteria. The genotype and allele frequency distribution of rs737337 (T/C) and rs2278426 (C/T) polymorphism in ANGPTL8 gene was studied. Participants with MetS were significantly older, had higher BMI, and rs737337 polymorphism frequency was significantly lower than in control. Furthermore, the TC + CC genotype and C allele of rs737337 (T/C) was associated with decreased risk of hypercholesterolemia and hyperglycemia [odds ratio (OR) 0.61, 95%CI 0.40-0.93, p = 0.016 and OR 0.58, 0.39-0.86, p = 0.007 respectively for hypercholesterolemia; and OR 0.66, 0.45-0.97, p = 0.032 and OR 0.65, 0.46-0.93; p = 0.016 respectively for hyperglycemia]. Similarly, CT, CT + TT genotype and T allele of rs2278426 (C/T) were associated with decreased risk of hyperglycemia (p < 0.05). In conclusion, the study suggests that the gene variants in SNPs rs 737337 (T/C) and rs 2278426 (C/T) are associated with lower risk of hypercholesterolemia and hyperglycemia. These findings supplement the growing literature supporting the role of ANGPTL8 in lipid and glucose metabolism.
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20
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Evidences for Expression and Location of ANGPTL8 in Human Adipose Tissue. J Clin Med 2020; 9:jcm9020512. [PMID: 32069954 PMCID: PMC7074245 DOI: 10.3390/jcm9020512] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 02/10/2020] [Indexed: 12/25/2022] Open
Abstract
The metabolism of triglycerides (TGs) is regulated, among others, by the lipoprotein lipase (LPL) that hydrolyses the TGs on endothelial cells. In turn, LPL is inhibited by the ANGPTLs family of proteins, such as ANGPTL3, 4, and, 8; the latter is the least known. In this work, we have tried to establish the expression and localisation of the Angiopoietin-like 8 (ANGPTL8) protein in the visceral adipose tissue (VAT) of morbid-obese and non-obese patients. 109 subjects (66 women and 43 men) undergoing laparoscopic surgery participated in this study. A blood sample and a portion of the VAT were obtained, and the patients were classified according to their Body Mass Index (BMI) as non-obese (19.5–30 kg/m2) and morbid-obese (40–50 kg/m2). No significant changes in ANGPTL8 plasma levels were determined by EIA in obese patients. The immunocytochemistry and Western blotting showed the presence of increased ANGPTL8 in morbid-obese patients (p < 0.05). In-situ hybridisation and a real time polymerase chain reaction (RT-PCR) confirmed that the mRNA that encodes ANGPTL8 was present in adipocytes, without differences in their nutritional state (p = 0.89), and even in the endothelial cells. Our data suggests that ANGPT8 plasmatic levels do not change significantly in patients with morbid obesity, although there is a modest difference related to gender. Besides, we demonstrate that in visceral adipose tissue, ANGPTL8 is well defined in the cytoplasm of adipocytes coexisting with perilipin-1 and its mRNA, also is present in endothelial cells. These findings suggest the possibility that among other functions, ANGPTL8 could perform either a paracrine and/or an endocrine role in the adipose tissue.
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Hou G, Tang Y, Ren L, Guan Y, Hou X, Song G. The ANGPTL8 rs2278426 (C/T) Polymorphism Is Associated with Prediabetes and Type 2 Diabetes in a Han Chinese Population in Hebei Province. Int J Endocrinol 2020; 2020:1621239. [PMID: 33343659 PMCID: PMC7728483 DOI: 10.1155/2020/1621239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/14/2020] [Accepted: 11/23/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Our aim was to investigate the association between the genetics of the angiopoietin protein-like 8 (ANGPTL8) rs2278426 (C/T) polymorphism with prediabetes (pre-DM) and type 2 diabetes (T2DM) in a Han Chinese population in Hebei Province, China. METHODS We enrolled 1,460 participants into this case-control study: healthy controls, n = 524; pre-DM, n = 460; and T2DM: n = 460. Ligase assays on blood samples from all participants were used to identify polymorphisms. Differences in genotype and allele distributions were compared by the chi-square test and one-way analysis of variance, and a post hoc pairwise analysis was performed using the Bonferroni test. The logistic regression technique was adjusted for age, sex, and body mass index. RESULTS The frequency of the TT (10.9%) genotype was significantly higher in pre-DM patients than in controls (odds ratio [OR] = 1.696, 95% confidence interval [CI] = 1.026-2.802, P=0.039). In the T2DM group, the CT (48%) and TT (15%) genotypes were significantly higher compared with those in the control group (CT : OR = 1.384, 95% CI = 1.013-1.890, P=0.041; TT : OR = 2.530, 95% CI = 1.476-4.334, P=0.001). The frequency of the T allele was significantly higher in the pre-DM (32.8%) and T2DM (39%) groups compared with the control group (26.9%) and was significantly associated with an increased risk of pre-DM (OR = 1.253, 95% CI = 1.017-1.544, P=0.034) and T2DM (OR = 1.518, 95% CI = 1.214-1.897, P=0.001). Furthermore, insulin levels in the pre-DM and T2DM groups were significantly decreased in those with the TT genotype compared with the CC and CT genotypes. CONCLUSION ANGPTL8 rs2278426 may be involved in the mechanism of insulin secretion and could lead to an increased risk of pre-DM and T2DM.
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Affiliation(s)
- Guangsen Hou
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Yong Tang
- Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, China
| | - Luping Ren
- Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, China
| | - Yunpeng Guan
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Xiaoyu Hou
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Guangyao Song
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China
- Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, China
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Guo C, Zhao Z, Deng X, Chen Z, Tu Z, Yuan G. Regulation of angiopoietin-like protein 8 expression under different nutritional and metabolic status. Endocr J 2019; 66:1039-1046. [PMID: 31631098 DOI: 10.1507/endocrj.ej19-0263] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing prevalence worldwide. Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein family, is involved in glucose metabolism, lipid metabolism, and energy homeostasis and believed to be associated with T2DM. Expression levels of ANGPTL8 are often significantly altered in metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus. Studies have shown that ANGPTL8, together with other members of this protein family, such as angiopoietin-like protein 3 (ANGPTL3) and angiopoietin-like protein 4 (ANGPTL4), regulates the activity of lipoprotein lipase (LPL), thereby participating in the regulation of triglyceride related lipoproteins (TRLs). In addition, members of the angiopoietin-like protein family are varyingly expressed among different tissues and respond differently under diverse nutritional and metabolic status. These findings may provide new options for the diagnosis and treatment of diabetes, metabolic syndromes and other diseases. In this review, the interaction between ANGPTL8 and ANGPTL3 or ANGPTL4, and the differential expression of ANGPTL8 responding to different nutritional and metabolic status during the regulation of LPL activity were reviewed.
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Affiliation(s)
- Chang Guo
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
| | - Zhicong Zhao
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
| | - Xia Deng
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
| | - Zian Chen
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China
| | - Zhigang Tu
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China
| | - Guoyue Yuan
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
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Thyroid Function in Patients with Type 2 Diabetes Mellitus and Diabetic Nephropathy: A Single Center Study. J Thyroid Res 2019; 2018:9507028. [PMID: 30631416 PMCID: PMC6304540 DOI: 10.1155/2018/9507028] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 10/29/2018] [Indexed: 12/12/2022] Open
Abstract
Background Diabetes mellitus is a common metabolic disease and the prevalence is increasing rapidly. Thyroid disorders including subclinical hypothyroidism (SCH) and low triiodothyronine (T3) syndrome are frequently observed in diabetic patients. We conducted a study to explore thyroid function in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods We included 103 healthy volunteers, 100 T2DM patients without DN, and 139 with DN. Physical examinations including body mass index and blood pressure and laboratory measurements including renal function, thyroid function, and glycosylated hemoglobin were conducted. Results Patients with DN had higher thyroid stimulating hormone (TSH) levels and lower free T3 (FT3) levels than those without DN (p < 0.01). The prevalence of SCH and low FT3 syndrome in patients with DN was 10.8% and 20.9%, respectively, higher than that of controls and patients without DN (p < 0.05). Through Pearson correlation or Spearman rank correlation analysis, in patients with DN, there were positive correlations in TSH with serum creatinine (r = 0.363, p = 0.013) and urinary albumin-to-creatinine ratio (r = 0.337, p = 0.004), and in FT3 with estimated glomerular filtration rate (eGFR) with statistical significance (r = 0.560, p < 0.001). Conclusions High level of TSH and low level of FT3 were observed in T2DM patients with DN. Routine monitoring of thyroid function in patients with DN is necessary, and management of thyroid dysfunction may be a potential therapeutic strategy of DN.
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Kahraman S, Altinova AE, Yalcin MM, Gulbahar O, Arslan B, Akturk M, Cakir N, Toruner FB. Association of serum betatrophin with fibroblast growth factor-21 in women with polycystic ovary syndrome. J Endocrinol Invest 2018; 41:1069-1074. [PMID: 29363048 DOI: 10.1007/s40618-018-0831-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 01/10/2018] [Indexed: 12/29/2022]
Abstract
PURPOSE Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently discovered members of hepatokine/adipokine family, have been proposed to be associated with some metabolic disorders in which insulin resistance plays a major role. METHODS We aimed to investigate serum betatrophin and FGF-21 concentrations in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, we recruited 31 women with PCOS and 34 women as healthy controls. Serum betatrophin level and its relationship with serum FGF-21 level as well as metabolic parameters were examined. RESULTS Serum betatrophin level was significantly higher in women with PCOS than the control group [1.10 (0.20-4.20) vs 0.70 (0.20-3.50) ng/ml, p = 0.004], whereas FGF-21 did not differ between the groups [74.80 (7.80-435.90) vs 119.30 (10.50-443.40) pg/ml, p = 0.13]. Serum betatrophin correlated positively with LH levels (r = 0.26, p = 0.03). After controlling BMI, there was a significant positive correlation between betatrophin and FGF-21 (r = 0.25, p = 0.04). Multivariate regression analysis revealed that FGF-21 and presence of PCOS were the significant predictors of betatrophin concentrations (R2 = 0.22, F = 2.56, p = 0.03). CONCLUSIONS Our results indicate that betatrophin levels are increased and associated with LH and FGF-21 levels, but not with insulin resistance, in women with PCOS.
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Affiliation(s)
- S Kahraman
- Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - A E Altinova
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Beşevler, 06500, Ankara, Turkey.
| | - M M Yalcin
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Beşevler, 06500, Ankara, Turkey
| | - O Gulbahar
- Department of Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - B Arslan
- Department of Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - M Akturk
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Beşevler, 06500, Ankara, Turkey
| | - N Cakir
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Beşevler, 06500, Ankara, Turkey
| | - F B Toruner
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Beşevler, 06500, Ankara, Turkey
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Wang H, Yu F, Zhang Z, Hou Y, Teng W, Shan Z, Lai Y. Effects of circulating member B of the family with sequence similarity 3 on the risk of developing metabolic syndrome and its components: A 5-year prospective study. J Diabetes Investig 2018; 9:782-788. [PMID: 29178453 PMCID: PMC6031514 DOI: 10.1111/jdi.12780] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 11/06/2017] [Accepted: 11/20/2017] [Indexed: 12/01/2022] Open
Abstract
AIMS/INTRODUCTION Member B of the family with sequence similarity 3 (FAM3B), also known as pancreatic-derived factor, is mainly synthesized and secreted by islet β-cells, and plays a role in abnormal metabolism of glucose and lipids. However, the prospective association of FAM3B with metabolic disorders remains unclear. The present study aimed to reveal the predictive relationship between pancreas-specific cytokine and metabolic syndrome (MetS). MATERIALS AND METHODS A total of 210 adults (88 men and 122 women) without MetS, aged between 40 and 65 years, were recruited and received a comprehensive health examination. Baseline serum FAM3B levels were determined by sandwich enzyme-linked immunosorbent assay. Subsequently, all participants underwent a follow-up examination after 5 years. MetS was identified in accordance with the International Diabetes Federation criteria. RESULTS During follow up, 35.7% participants developed MetS. In comparison with the non-MetS group, participants with MetS had an increased serum FAM3B at baseline (21.85 ng/mL [19.38, 24.17 ng/mL] vs 28.56 ng/mL [25.32, 38.10 ng/mL], P < 0.001). Moreover, serum FAM3B was significantly associated with variations in fasting plasma insulin (r = -0.306, P < 0.001), homeostasis model assessment of β-cell function (r = -0.328, P < 0.001) and homeostasis model assessment of insulin resistance (r = -0.191, P = 0.006). Furthermore, a positive correlation between baseline FAM3B and the incidence of MetS was observed, even after multivariable adjustment (relative risk 1.23 [1.15, 1.31], P < 0.001). Furthermore, the optimal cut-off values of FAM3B was 23.98 ng/mL for predicting MetS based on the Youden Index. CONCLUSIONS Elevated circulating FAM3B might be considered as a predictor of newly-onset MetS and its progression.
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Affiliation(s)
- Haoyu Wang
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
| | - Fadong Yu
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
| | - Zhuo Zhang
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
| | - Yuanyuan Hou
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
| | - Weiping Teng
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
| | - Zhongyan Shan
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
| | - Yaxin Lai
- Department of Endocrinology and MetabolismInstitute of EndocrinologyLiaoning Provincial Key Laboratory of Endocrine DiseasesThe First Affiliated Hospital of China Medical UniversityChina Medical UniversityShenyangLiaoningChina
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Huang Y, Chen X, Chen X, Feng Y, Guo H, Li S, Dai T, Jiang R, Zhang X, Fang C, Hu J. Angiopoietin-like protein 8 in early pregnancy improves the prediction of gestational diabetes. Diabetologia 2018; 61:574-580. [PMID: 29167926 DOI: 10.1007/s00125-017-4505-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 10/16/2017] [Indexed: 12/13/2022]
Abstract
AIMS/HYPOTHESIS Screening high-risk individuals for gestational diabetes mellitus (GDM) in early pregnancy conventionally relies on established maternal risk factors; however, the sensitivity and specificity of these factors are not satisfactory. The present study aimed to determine whether the concentration of angiopoietin-like protein 8 (ANGPTL8), either alone or combined with other risk factors in early pregnancy, could be used to predict subsequent GDM. METHODS From August 2015 to January 2016, 474 women receiving prenatal care at around 12-16 weeks of gestation were recruited into the study. ANGPTL8 levels were measured at the first prenatal visit. All the participants received a 75 g OGTT during weeks 24-28 of gestation. RESULTS ANGPTL8 levels in early pregnancy were considerably higher in women who developed GDM than those who maintained normal glucose tolerance (2822 ± 938 vs 2120 ± 1118 pg/ml, respectively; p < 0.0001). Multivariable logistic regression revealed that ANGPTL8 levels were significantly associated with risk of GDM independent of conventional risk factors. In addition, women in the highest quartile of ANGPTL8 concentration had an 8.75-fold higher risk of developing GDM compared with women in the lowest quartile (OR8.75, 95%CI 2.43, 31.58). More importantly, incorporating ANGPTL8 into the conventional prediction model significantly increased the AUC for prediction of GDM (0.772vs 0.725; p = 0.019). CONCLUSIONS Our study suggests that ANGPTL8 levels in early pregnancy are significantly and independently associated with risk of GDM at 24-28 weeks of gestation. Combining ANGPTL8 levels with conventional risk factors could thus improve the prediction of GDM.
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Affiliation(s)
- Yun Huang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Xin Chen
- Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Jiangsu, People's Republic of China
| | - Xiaohong Chen
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Yu Feng
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Heming Guo
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Sicheng Li
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Ting Dai
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Rong Jiang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Xiaoyan Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China
| | - Chen Fang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China.
| | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People's Republic of China.
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Lee SH, Rhee M, Kwon HS, Park YM, Yoon KH. Serum Betatrophin Concentrations and the Risk of Incident Diabetes: A Nested Case-Control Study from Chungju Metabolic Disease Cohort. Diabetes Metab J 2018; 42:53-62. [PMID: 29199405 PMCID: PMC5842301 DOI: 10.4093/dmj.2018.42.1.53] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/26/2017] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Betatrophin is a newly identified hormone derived from the liver and adipose tissue, which has been suggested to regulate glucose and lipid metabolism. Circulating levels of betatrophin are altered in various metabolic diseases, although the results are inconsistent. We aimed to examine whether betatrophin is a useful biomarker in predicting the development of diabetes. METHODS A nested case-control study was performed using a prospective Chungju Metabolic disease Cohort Study. During a 4-year follow-up period, we analyzed 167 individuals who converted to diabetes and 167 non-converters, who were matched by age, sex, and body mass index. Serum betatrophin levels were measured by an ELISA (enzyme-linked immunosorbent assay). RESULTS Baseline serum betatrophin levels were significantly higher in the converter group compared to the non-converter group (1,315±598 pg/mL vs. 1,072±446 pg/mL, P<0.001). After adjusting for age, sex, body mass index, fasting plasma glucose, systolic blood pressure, total cholesterol, and family history of diabetes, the risk of developing diabetes showed a stepwise increase across the betatrophin quartile groups. Subjects in the highest baseline quartile of betatrophin levels had more than a threefold higher risk of incident diabetes than the subjects in the lowest quartile (relative risk, 3.275; 95% confidence interval, 1.574 to 6.814; P=0.010). However, no significant relationships were observed between serum betatrophin levels and indices of insulin resistance or β-cell function. CONCLUSION Circulating levels of betatrophin could be a potential biomarker for predicting new-onset diabetes. Further studies are needed to understand the underlying mechanism of this association.
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Affiliation(s)
- Seung Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Marie Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyuk Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Moon Park
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | - Kun Ho Yoon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Luo M, Peng D. ANGPTL8: An Important Regulator in Metabolic Disorders. Front Endocrinol (Lausanne) 2018; 9:169. [PMID: 29719529 PMCID: PMC5913278 DOI: 10.3389/fendo.2018.00169] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 03/28/2018] [Indexed: 12/26/2022] Open
Abstract
Long-term controversy regarding the role of angiopoietin-like protein 8 (ANGPTL8) in beta-cell proliferation and diabetes progression made it a research spotlight. Recently, the controversy was resolved. Although ANGPTL8 could not control beta-cell expansion and islet function, ANGPTL8 was still considered as a novel but atypical member in the ANGPTL family because of its unique structure and crucial effects on lipid metabolism. Besides, ANGPTL8 also participated in some other disorders such as non-alcoholic fatty liver disease and renal dysfunction. Understanding the features of ANGPTL8 may offer new diagnostic and therapeutic approaches to metabolic-related diseases. Therefore, we reviewed most recent findings about ANGPTL8 and aimed to provide an integrated picture of ANGPTL8.
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Wang S, Hong X, Tu Z, Yuan G. Angiopoietin-like protein 8: An attractive biomarker for the evaluation of subjects with insulin resistance and related disorders. Diabetes Res Clin Pract 2017; 133:168-177. [PMID: 28965028 DOI: 10.1016/j.diabres.2017.08.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 08/01/2017] [Accepted: 08/30/2017] [Indexed: 12/28/2022]
Abstract
Insulin resistance is prevalent worldwide and is associated with many metabolic diseases, in particular, type 2 diabetes mellitus (T2DM), obesity, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS). Angiopoietin-like protein 8 (ANGPTL8), a newly-identified secreted protein composing of 198 amino acids, is enriched in the liver of human. Considering its promising potential for β-cell proliferation and therapeutic prospect for diabetes, ANGPTL8 has aroused extensive interests. However, a recent collaborative study confirmed that ANGPTL8 didn't stimulate dramatic β-cell regeneration. At present, a controversial scientific discussion on whether and how ANGPTL8 regulate insulin resistance has been ongoing. Interestingly, several in vitro and in vivo studies have suggested the complex roles of ANGPTL8 in insulin resistance. Data resulting from cross-sectional and longitudinal researches in human individuals involving the influence of ANGPTL8 on the development of insulin resistance were controversial. We therefore summarize currently clinical literature to exploit whether this exciting hormone could be applied for clinical application asa potential clinical biomarker to predict insulin resistance and related disorders.
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Affiliation(s)
- Su Wang
- Department of Endocrinology, Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China; Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Xiafei Hong
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Zhigang Tu
- Institute of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Guoyue Yuan
- Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
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Wang H, Liu A, Zhao T, Gong X, Pang T, Zhou Y, Xiao Y, Yan Y, Fan C, Teng W, Lai Y, Shan Z. Comparison of anthropometric indices for predicting the risk of metabolic syndrome and its components in Chinese adults: a prospective, longitudinal study. BMJ Open 2017; 7:e016062. [PMID: 28928179 PMCID: PMC5623484 DOI: 10.1136/bmjopen-2017-016062] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVES Our study aimed to distinguish the ability of anthropometric indices to assess the risk of metabolic syndrome (MetS). DESIGN Prospective cohort study. SETTING Shenyang, China. PARTICIPANTS A total of 379 residents aged between 40 and 65 were enrolled. 253 of them were free of MetS and had been followed up for 4.5 years. METHODS At baseline, all the participants underwent a thorough medical examination. A variety of anthropometric parameters were measured and calculated, including waist circumference (WC), body mass index (BMI), a body shape index (ABSI), abdominal volume index (AVI), body adiposity index, body roundness index, conicity index, waist-to-hip ratio and visceral adiposity index (VAI). After 4.5 year follow-up, we re-examined whether participants were suffering from MetS. A receiver operating characteristic (ROC) curve was applied to examine the potential of the above indices to identify the status and risk of MetS. OUTCOMES Occurrence of MetS. RESULTS At baseline, 33.2% participants suffered from MetS. All of the anthropometric indices showed clinical significance, and VAI was superior to the other indices as it was found to have the largest area under the ROC curve. After a 4.5 year follow-up, 37.8% of men and 23.9% of women developed MetS. ROC curve analysis suggested that baseline BMI was the strongest predictor of MetS for men (0.77 (0.68-0.85)), and AVI was the strongest for women (0.72 (0.64-0.79)). However, no significant difference was observed between WC and both indices. In contrast, the baseline ABSI did not predict MetS in both genders. CONCLUSIONS The present study indicated that these different indices derived from anthropometric parameters have different discriminatory abilities for MetS. Although WC did not have the largest area under the ROC curve for diagnosing and predicting MetS, it may remain a better index of MetS status and risk because of its simplicity and wide use.
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Affiliation(s)
- Haoyu Wang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Aihua Liu
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Tong Zhao
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Xun Gong
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Tianxiao Pang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Yingying Zhou
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Yue Xiao
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Yumeng Yan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Chenling Fan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Weiping Teng
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Yaxin Lai
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
| | - Zhongyan Shan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China
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Wang H, Liu A, Zhou Y, Xiao Y, Yan Y, Zhao T, Gong X, Pang T, Fan C, Zhao J, Teng W, Shan Z, Lai Y. The correlation between serum free thyroxine and regression of dyslipidemia in adult males: A 4.5-year prospective study. Medicine (Baltimore) 2017; 96:e8163. [PMID: 28953665 PMCID: PMC5626308 DOI: 10.1097/md.0000000000008163] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests that a more flexible lipid-lowering therapy may be appropriate for patients with high-normal FT4.
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Affiliation(s)
- Haoyu Wang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Aihua Liu
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Yingying Zhou
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Yue Xiao
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Yumeng Yan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Tong Zhao
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Xun Gong
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Tianxiao Pang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Chenling Fan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University
- Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Weiping Teng
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Zhongyan Shan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
| | - Yaxin Lai
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning
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Liu D, Li S, He H, Yu C, Li X, Liang L, Chen Y, Li J, Li J, Sun X, Tian H, An Z. Increased circulating full-length betatrophin levels in drug-naïve metabolic syndrome. Oncotarget 2017; 8:17510-17517. [PMID: 28177922 PMCID: PMC5392266 DOI: 10.18632/oncotarget.15102] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 01/23/2017] [Indexed: 02/05/2023] Open
Abstract
Betatrophin is a newly identified circulating adipokine playing a role in the regulation of glucose homeostasis and lipid metabolism. But its role in metabolic syndrome (MetS) remains unknown. Therefore, we aimed to compare the circulating betatrophin concentrations between patients with MetS and healthy controls. We recruited 47 patients with MetS and 47 age and sex matched healthy controls. Anthropometric and biochemical measurements were performed, and serum betatrophin levels were detected by ELISA. Full-length betatrophin levels in patients with MetS were significantly higher than those in controls (694.84 ± 365.51 pg/ml versus 356.64 ± 287.92 pg/ml; P <0.001). While no significant difference of total betatrophin levels was found between the two groups (1.20 ± 0.79 ng/ml versus 1.31 ± 1.08 ng/ml; P = 0.524). Full-length betatrophin level was positively correlated with fasting plasma glucose (FPG) (r = 0.357, P = 0.014) and 2-hour plasma glucose (2hPG) (r = 0.38, P <0.01). Binary logistic regression models indicated that subjects in the tertile of the highest full-length betatrophin level experienced higher odds of having MetS (OR, 8.6; 95% CI 2.8-26.8; P <0.001). Our study showed that full-length betatrophin concentrations were increased in drug-naïve MetS patients.
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Affiliation(s)
- Dan Liu
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Sheyu Li
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - He He
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chuan Yu
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaodan Li
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Libo Liang
- Department of General Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yi Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jianwei Li
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jianshu Li
- Department of Biomedical Polymer and Artificial Organs, College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan, China
| | - Xin Sun
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Haoming Tian
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhenmei An
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Lai Y, Wang H, Xia X, Wang Z, Fan C, Wang H, Zhang H, Ding S, Teng W, Shan Z. Serum fibroblast growth factor 19 is decreased in patients with overt hypothyroidism and subclinical hypothyroidism. Medicine (Baltimore) 2016; 95:e5001. [PMID: 27684859 PMCID: PMC5265952 DOI: 10.1097/md.0000000000005001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
As a newly emerging metabolic regulator, accumulating evidence suggests that the circulating fibroblast growth factor 19 (FGF19) level correlated with lipid and glucose metabolism. Several independent groups have found that FGF19 was highly likely associated with multiple metabolic disorders. Thyroid dysfunction is believed to be associated with metabolism diseases. However, to date, few studies have investigated the role of FGF19 in patients with thyroid dysfunctions. For this purpose, a cross-sectional study was done to estimate the role of FGF19 in patients with different thyroid functions. Compared with the healthy control, the present study revealed that serum FGF19 levels were significantly decreased in overt hypothyroidism patients (78.7 [52.7-121.2] vs 292.4 [210.2-426.5] pg/mL, P <0.001). FGF19 concentration was also lower in the subclinical hypothyroidism group than it was in the healthy control group (95.8 [71.7-126.3] vs 292.4 [210.2-426.5] pg/mL, P <0.001). However, there was no significant difference in FGF19 level between the isolated thyroid autoantibody positive group and the healthy control group (252.0 [205.9-353.5] vs 292.4 [210.2-426.5] pg/mL, P >0.05). Also, serum thyroid stimulating hormone (TSH) was an independent predictor of FGF19. In conclusion, thyroid insufficiency but not thyroid autoimmunity may have impacted serum FGF19 concentrations. As the role of FGF19 is becoming more and more important in the pathogenesis of many metabolic diseases, we proposed that the thyroid hormone level should be taken into account when the serum concentration is explained. Further studies are needed to elucidate the role of FGF19 in the development of hypothyroidism.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Zhongyan Shan
- The Liaoning Provincial Key Laboratory of Endocrine Disease, Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China
- Correspondence: Zhongyan Shan, The Liaoning Provincial Key Laboratory of Endocrine Disease, Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, 110001, P.R. China (e-mail: )
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