Visualizing the regulatory role of Angiopoietin-like protein 8 (ANGPTL8) in glucose and lipid metabolic pathways

Siddiqa, Amnah; Cirillo, Elisa; Tareen, Samar; Ali, Amjad; Kutmon, Martina; Eijssen, Lars; Ahmad, Jamil; Evelo, Chris T.; Coort, Susan L.

doi:10.1016/j.ygeno.2017.06.006

Cited by 33 publications

(48 citation statements)

References 68 publications

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“…A study related to human health found that inflammation had a significant contribution to metabolic diseases (Gifford et al., ), which might help to explain the effect of this gene on cattle growth development. Consistent with the studies in humans and mice (Siddiqa et al., ; Zhang, ), bovine ANGPTL8 was highly expressed in back fat and liver. Therefore, we speculate these three genes may affect the energy metabolism of cattle and thus affect the growth traits.…”

Section: Discussionsupporting

confidence: 87%

Tissue expression and variation analysis of three bovine adipokine genes revealed their effect on growth traits in native Chinese cattle

Chen

Han

et al. 2018

Reprod Domestic Animals

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Adipokines play a crucial role in the regulation of energy homeostasis; however, little is known about genetic alterations in this family that may contribute to economic traits in cattle. Therefore, this study conducts transcript profiles, variations and association studies of three major adipokines, leptin (LEP), tumour necrosis factor (TNF) and angiopoietin-like protein 8 (ANGPTL8), to evaluate their effects on native Chinese cattle. Using quantitative real-time PCR, the study revealed that the bovine LEP was expressed primarily in the back and visceral fat, while TNF was predominantly expressed in spleen and ANGPTL8 was mainly expressed in back fat and liver. Five single nucleotide polymorphisms (SNPs) including two missense SNPs (SNP1: g.12254T>C and SNP2: g.14177C>T) in LEP, a synonymous SNP (SNP3: g.2130A>G) in TNF and two SNPs (SNP4: g.629G>A and SNP5: g.884T>C) in the 5'UTR of ANGPTL8 were identified and genotyped in 537 individuals from six Chinese cattle breeds. Bioinformatics analysis revealed that SNP1 might disrupt the efficient binding of LEP to its receptor, SNP3 might affect translation efficiency of TNF, and SNP4 and SNP5 were likely to affect stability, splicing and nuclear export of ANGPTL8 mRNA. Consistently, association studies indicated that three SNPs (SNP1, SNP3 and SNP5) were significantly associated with body weight, heart girth, average daily gain, hip width and body length in 100 Nanyang cattle (p < 0.05). Overall, our results support the view that LEP, TNF and ANGPTL8 could be used as biomarkers to improve the growth performance in Chinese cattle selection programmes.

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Section: Discussionsupporting

confidence: 87%

Tissue expression and variation analysis of three bovine adipokine genes revealed their effect on growth traits in native Chinese cattle

Chen

Han

et al. 2018

Reprod Domestic Animals

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“…In animal studies, nutritional intake, lipogenesis, obesity, and insulin resistance increase ANGPTL8 mRNA expression in liver and fat tissue, whereas energy restriction and lipolysis suppress the ANGPTL8 transcript level [34,35]. In human, serum ANGPTL8 levels are increased in obesity and T2D and exert a dual role in glucose and lipids metabolism, thereby establishing it as a potential therapeutic target in the treatment of obesity and T2D [4,5,17]. Therefore, the role and regulation of ANGPTL8, particularly in relation to weight loss, have been highlighted recently.…”

Section: Discussionmentioning

confidence: 99%

“…Adipose tissue is one of the principal organs of involved in the regulation of ANGPTL8 [4,7,22,[32][33][34]. ANGPTL8 mRNA was abundantly expressed in human adipose tissue [4,7,22], and the serum levels of ANGPTL8 were found to be increased in individuals with obesity and T2D and positively correlated with waist and BMI [21,45,48]. The increase in ANGPTL8 levels can be reduced in obese or obese T2D subjects who lost significant adipose tissue after bariatric surgery [18,22].…”

Section: Discussionmentioning

confidence: 99%

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Effects of a diet with or without physical activity on angiopoietin-like protein 8 concentrations in overweight/obese patients with newly diagnosed type 2 diabetes: a randomized controlled trial

Yuan

Wang

et al. 2019

Endocr J

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Angiopoietin-like protein 8 (ANGPTL8) is a newly discovered adipokine plays an important role in energy homoeostasis, obesity and type 2 diabetes (T2D). Although lifestyle modification in obesity and T2D is known to offer metabolic benefits, there is paucity of comprehensive data on change in ANGPTL8. We investigated the effect of lifestyle intervention on ANGPTL8 concentrations. 384 obese/overweight adults with newly diagnosed T2D were randomly assigned (1:1:1) to diet (n = 128), diet + activity (n = 128) or usual care (control, n = 128) groups. All patients received usual care. Besides, the diet group received a calorie-restricted diet aiming for a weight loss of 5-10%. The diet + activity group additionally received a pedometer-based walking program. Primary outcome was change in ANGPTL8 concentration at 6 months. Data were analyzed according to intention-to-treat. From baseline to 6 months, the median ANGPTL8 level changed from 804.38 pg/mL to 792.86 pg/mL in control group. Compared with control, ANGPTL8 decreased with diet (baselineadjusted between-group difference was-121.00 pg/mL, 95% CI-177.47 to-64.53; p < 0.0001) and diet + activity (-126.16 pg/mL,-181.21 to-71.11; p < 0.0001). There was no greater effect of diet + activity compared with diet (-5.16 pg/mL,-53.63 to 43.31; p = 0.8348). Both effects disappeared after adjusting for change in body fat, but did not differ significantly when adjusting for physical activity. A 6-month intervention inducing weight loss by a calorie-restricted diet or diet + activity, resulted in significant decrease on ANGPTL8 concentration. These effects were established by change in total body fat, and not by change in physical activity.

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“…[2016] [19,22]. Also, Yamada et al [2015] reported higher levels of serum betatrophin levels in cases with T2DMthan the healthy group [32]. Moreover, Abu-Farha et al…”

Section: T2dmmentioning

confidence: 99%

Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children

Mohany

Alrugaie

Al‐Wutayd

et al. 2020

Preprint

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Background: This study tested the association between serum levels of microRNA-486, -146b and -15b and betatrophin in normal and obese children with/without type 2 diabetes mellitus (T2DM).Methods: the study included 120 children; divided into three groups: G1 (50 healthy), G2 (35 obese) and G3 (35 obese with T2DM). The levels of microRNA-486, 146b and 15b and serum betatrophin were measured by their corresponding methods.Results: serum microRNA-486, -146b, -15b and betatrophin levels were significantly high in G3 followed by G2 then G1 (p=0.002, >0.001, >0.001, and >0.001, respectively). Especially in G3, these levels correlated positively with the BMI percentile (r=0.44, 0.58, 0.38, and 0.46, p=0.007, >0.001, 0.021, and 0.005, respectively), serum glucose (r=0.56, 0.49, 0.82, 0.60, and 0.42, p>0.001, 0.003, >0.001, and >0.001, respectively) and HbA1c% (r=0.56, 0.39, 0.66, and 0.42, p>0.001, 0.019, >0.001, and 0.032, respectively) while, showed negative correlations with correlated with serum insulin levels (r=-0.37, -0.42, -0.58, and -0.41, p=0.021, 0.012, >0.001 and 0.013, respectively) and with serum C-peptide levels (r=-0.76, -0.50, -0.35 and -0.42, p>0.001, 0.002, 0.036 and 0.011, respectively). Serum betatrophin levels correlated positively with microRNA-486, -146b and -15b levels in G2 (r=0.35, 0.80, and 0.67, p= 0.036, >0.001, and,>0.001, respectively), and in G3 (r=0.57, 0.36, and 0.38, p >0.001, 0.029 and, 0.023, respectively).Conclusions: Circulating microRNA-486, 146b and 15b increase significantly in obese children with T2DM and these levels correlate positively with serum betatrophin levels. Further studies are required to test the role of targeting of these microRNAs and betatrophin in the timely management of obesity and/or T2DM in children.

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Visualizing the regulatory role of Angiopoietin-like protein 8 (ANGPTL8) in glucose and lipid metabolic pathways

Cited by 33 publications

References 68 publications

Tissue expression and variation analysis of three bovine adipokine genes revealed their effect on growth traits in native Chinese cattle

Tissue expression and variation analysis of three bovine adipokine genes revealed their effect on growth traits in native Chinese cattle

Effects of a diet with or without physical activity on angiopoietin-like protein 8 concentrations in overweight/obese patients with newly diagnosed type 2 diabetes: a randomized controlled trial

Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children

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