The Relationship between Circulating ANGPTL8/Betatrophin Concentrations and Adult Obesity: A Meta-Analysis

Ye, Jingjing; Qin, Yu; Wang, Dong; Yang, Licong; Yuan, Guoyue

doi:10.1155/2019/5096860

Cited by 15 publications

(13 citation statements)

References 39 publications

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“…49 In clinical studies, levels of ANGPTL8 in the circulation of obese and overweight patients increases significantly. 40 The T allele at rs2278426 of ANGPTL8 represents Arg59Trp replacement, but the circulating level of ANGPTL8 is not affected. 50 Bioinformatis analysis has shown that Arg59Trp replacement caused by the T allele can reduce stability of the ANGPTL8 protein.…”

Section: Discussionmentioning

confidence: 99%

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ANGPTL8 Gene Polymorphism rs2278426 Is Related to Carotid Intima–Media Thickness in T2DM

Guo¹,

Zhao²,

Ding³

et al. 2020

DMSO

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Aim: ANGPTL8 is a cytokine expressed and secreted by liver and adipose tissue, and is involved in glucose, lipid, and energy metabolism. Although studies have shown that ANGPTL8 is elevated in type 2 diabetes mellitus (T2DM) and cardiovascular disease, few have examined the association between ANGPTL8 single-nucleotide polymorphisms and the risk of macrovascular complications in T2DM patients. This study aimed to explore the relationship between rs2278426 and carotid intima-media thickening (cIMT) in T2DM. Methods: A total of 217 T2DM patients and 201 healthy control subjects with normal glucose tolerance were recruited in the study. T2DM patients were divided into two groups: T2DM patients without cIM thickening (cIMT <1 mm, 109 cases) and T2DM patients with cIM thickening (cIMT ≥1 mm, 108 cases). rs2278426 genotypes in all 418 subjects were determined and the risk of T2DM and T2DM with cIM thickening analyzed. Results: CT+TT-genotype frequency in T2DM was higher than in controls with normal glucose tolerance, and the proportion of the CT+TT genotype in the group with cIMT was higher than in the group (P<0.05). In addition, T alleles were associated with waist:hip ratio, triglycerides, high density-lipoprotein cholesterol, plasma glucose at 2 hours' oral glucose tolerance, and homeostatic model assessment of insulin resistance (P<0.05). Conclusion: Generally, carriers of the T allele at rs2278426 are more likely to develop T2DM, and the risk of cIM thickening is significantly increased for T-allele carriers with T2DM, which indicates an increased risk of macroangiopathy.

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Section: Discussionmentioning

confidence: 99%

“…31,39 Clinical studies have shown that the level of circulating ANGPTL8 in obese and overweight patients is significantly increased. 40 Therefore, ANGPTL8 may be involved in the occurrence and development of T2DM and its macrovascular lesions through its important regulatory role in glucose and lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

ANGPTL8 Gene Polymorphism rs2278426 Is Related to Carotid Intima–Media Thickness in T2DM

Guo¹,

Zhao²,

Ding³

et al. 2020

DMSO

Self Cite

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“…Early studies of betatrophin levels in various forms of human insulin resistance were quite conflictory, partly due to the differences in measurement methods[ 82 ]. Later studies using more standardized methods for measuring betatrophin were summarized by several meta-analyses on the correlation of circulating betatrophin levels and type 2 diabetes, gestational diabetes, polycystic ovary syndrome (PCOS), and obesity — all conditions with insulin resistance[ 91 - 95 ]. Xu et al [ 91 ] analyzed 25 such studies and showed a positive and significant correlation between circulating betatrophin levels and insulin resistance.…”

Section: Novel Endocrine Functions Of the Livermentioning

confidence: 99%

“…Varikasuvu et al [ 94 ] analyzed 11 studies on betatrophin in PCOS and concluded that betatrophin is significantly elevated in PCOS. Similarly, Ye et al [ 95 ] analyzed 6 studies on betatrophin in obesity and concluded that betatrophin is significantly elevated in obesity. Thus, overall, circulating betatrophin is likely a marker of insulin resistance in humans.…”

Section: Novel Endocrine Functions Of the Livermentioning

confidence: 99%

Newly discovered endocrine functions of the liver

Rhyu¹,

Yu²

2021

WJH

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The liver, the largest solid visceral organ of the body, has numerous endocrine functions, such as direct hormone and hepatokine production, hormone metabolism, synthesis of binding proteins, and processing and redistribution of metabolic fuels. In the last 10 years, many new endocrine functions of the liver have been discovered. Advances in the classical endocrine functions include delineation of mechanisms of liver production of endocrine hormones [including 25-hydroxyvitamin D, insulin-like growth factor 1 (IGF-1), and angiotensinogen], hepatic metabolism of hormones (including thyroid hormones, glucagon-like peptide-1, and steroid hormones), and actions of specific binding proteins to glucocorticoids, sex steroids, and thyroid hormones. These studies have furthered insight into cirrhosis-associated endocrinopathies, such as hypogonadism, osteoporosis, IGF-1 deficiency, vitamin D deficiency, alterations in glucose and lipid homeostasis, and controversially relative adrenal insufficiency. Several novel endocrine functions of the liver have also been unraveled, elucidating the liver’s key negative feedback regulatory role in the pancreatic α cell-liver axis, which regulates pancreatic α cell mass, glucagon secretion, and circulating amino acid levels. Betatrophin and other hepatokines, such as fetuin-A and fibroblast growth factor 21, have also been discovered to play important endocrine roles in modulating insulin sensitivity, lipid metabolism, and body weight. It is expected that more endocrine functions of the liver will be revealed in the near future.

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“…Some studies have shown that ANGPTLs play an important role in insulin resistance, glucose metabolism, and hormone regulation [ 10 – 12 ]. Notably, ANGPTL8, also known as betatrophin, C19ORF80, or lipasin [ 13 ], regulates triglyceride metabolism by interacting with ANGPTL3 and ANGPTL4 to inhibit lipoprotein lipase (LPL) activity [ 14 – 16 ]. This further indicates that ANGPTLs are also closely related to lipid metabolism and may be an important link in metabolic syndrome [ 17 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating angiopoietin-like proteins in metabolic-associated fatty liver disease: a systematic review and meta-analysis

Liu

Zhang

et al. 2021

Lipids Health Dis

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Background Angiopoietin-like proteins (ANGPTLs) are closely related to insulin resistance and lipid metabolism, and may be a key in metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) (newly named metabolic-associated fatty liver disease (MAFLD)) is based on metabolic dysfunction. There may be some correlation between ANGPTLs and MAFLD, but the specific correlation is unclear. This study aims to explore the predictive role of ANGPTLs in MAFLD and its progression. Methods Seven databases (PubMed, EMBASE, Cochrane Library, CNKI, WANFANG, CBM and Clinicaltrials.gov) were searched with free terms and MeSH terms. The random-effects model was used to pool the data, and Standardized Mean Difference (SMD) and 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the article selection. RevMan 5.3, Stata 16 and MetaXL software were applied to analyse the data and the GRADE system was utilized to assess the certainty of evidence. Results After reviewing 823 related articles, 13 studies (854 cases and 610 controls) met the inclusion criteria, and contributed to this meta-analysis. The results showed that circulating ANGPTL8 level was significantly elevated in the MAFLD group than in the healthy control group (SMD = 0.97 pg/mL, 95%CI: 0.77, 1.18). Conversely, there was no significant difference in the ANGPTL4 (SMD = 0.11 ng/mL, 95%CI: − 0.32, 0.54) and ANGPTL3 (SMD = − 0.95 ng/mL, 95%CI: − 4.38, 2.48) between the two groups. Subgroup analysis showed that: 1) the MAFLD group had significantly higher ANGPTL8 levels than the healthy control group in Asian and other races; 2) the ANGPTL8 levels in Body Mass Index (BMI) > 25 kg/m2 patients with MAFLD were higher than those in the healthy control group; 3) the higher ANGPTL8 levels were observed in moderate to severe MAFLD group than the healthy control group. Meta-regression demonstrated that BMI might effectively explain the high heterogeneity. No significant publication bias existed (P > 0.05). The certainty of evidence was assessed as very low by the GRADE system. Conclusions The ANGPTLs may be related to MAFLD. The increased ANGPTL8 level may be positively correlated with different situations of MAFLD, which may act as a potential indicator to monitor the development trends.

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The Relationship between Circulating ANGPTL8/Betatrophin Concentrations and Adult Obesity: A Meta-Analysis

Cited by 15 publications

References 39 publications

<p><em>ANGPTL8</em> Gene Polymorphism rs2278426 Is Related to Carotid Intima–Media Thickness in T2DM</p>

<p><em>ANGPTL8</em> Gene Polymorphism rs2278426 Is Related to Carotid Intima–Media Thickness in T2DM</p>

Newly discovered endocrine functions of the liver

Circulating angiopoietin-like proteins in metabolic-associated fatty liver disease: a systematic review and meta-analysis

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