Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase

Zhang, Yuan; Li, Shiwu; Donelan, William; Xie, Chao; Wang, Hai; Wu, Qi; Purich, Daniel L.; Reeves, Westley H.; Tang, Dongqi; Yang, Lijun

doi:10.1016/j.bbalip.2015.11.003

Cited by 41 publications

(31 citation statements)

References 41 publications

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“…Study revealed that ANGPTL8 also regulates lipid autophagy by inducing catabolism of lipid droplets in hepatocytes [35]. Furthermore, ANGPTL8 could activate ERK signaling pathway to stimulate the expression of Egr1, which in turn lead to down-regulation of adipose triglyceride lipase and subsequently lipid accumulation in adipose tissue [49]. This provides another insight of regulation of lipid metabolism by ANGPTL8 protein.…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%

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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“…In this study, we also found that correlations between betatrophin and body fat distribution indices only existed in the NGT group, not the IGT group. We speculate that the different glucose metabolic states of the patients could affect their inflammatory state, since increased inflammatory cytokine levels affect betatrophin synthesis [14,[42][43][44], accordingly the relationship between betatrophin and body fat distribution cannot be observed. It should be noted that the hypothesis requires further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Circulating betatrophin/ANGPTL8 levels correlate with body fat distribution in individuals with normal glucose tolerance but not those with glucose disorders

et al. 2020

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Background: The relationship between betatrophin/ANGPTL8 and obesity has been investigated using body mass index (BMI); however, since BMI reflects overall adiposity rather than body fat distribution, it remains unclear whether fat deposition in different areas of the body affects betatrophin expression. Here, we investigated the correlation between circulating betatrophin levels and body fat distribution in patients with different glucose tolerance. Methods: We performed a cross-sectional study in 128 participants with impaired glucose tolerance (IGT; n = 64) or normal glucose tolerance (NGT; n = 64). Circulating betatrophin levels were detected by enzyme-linked immunosorbent assay (ELISA). Body fat distribution (subcutaneous, visceral, and limb fat) was measured by magnetic resonance imaging (MRI) and a body fat meter.Results: After controlling for age, sex, and BMI, betatrophin was correlated positively with visceral adipose tissue-tosubcutaneous adipose tissue ratio (VAT/SAT ratio; r = 0.339, p = 0.009) and negatively with body fat ratio (BFR; r = − 0.275, p = 0.035), left lower limb fat ratio (LLR; r = − 0.330, p = 0.011), and right lower limb fat ratio (RLR; r = − 0.288, p = 0.027) in the NGT group, with these correlations remaining after controlling for triglycerides. VAT/SAT ratio (standardized β = 0.419, p = 0.001) was independently associated with serum betatrophin levels; however, betatrophin was not associated with body fat distribution variables in the IGT group.Conclusions: Circulating betatrophin levels correlated positively with VAT/SAT ratio and negatively with lower limb fat, but not with subcutaneous or upper limb fat, in individuals with normal glucose tolerance. Thus, betatrophin may be a potential biomarker for body fat distribution in individuals without glucose disorders.

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“…17,18 It has also been recently shown that ANGPTL8 induces intracellular TG accumulation by downregulating the adipose triglyceride lipase (ATGL). 19 Moreover, several recent studies show a positive association of serum ANGPTL8 with NAFLD, 20e22 but little is known about a potential pathogenic link between ANGPTL8 and NAFLD.…”

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confidence: 99%

Angiopoietin-Like Protein 8 Is a Novel Vitamin D Receptor Target Gene Involved in Nonalcoholic Fatty Liver Pathogenesis

García‐Monzón

Petrov

Rey

et al. 2018

The American Journal of Pathology

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Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase

Cited by 41 publications

References 41 publications

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

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

Circulating betatrophin/ANGPTL8 levels correlate with body fat distribution in individuals with normal glucose tolerance but not those with glucose disorders

Angiopoietin-Like Protein 8 Is a Novel Vitamin D Receptor Target Gene Involved in Nonalcoholic Fatty Liver Pathogenesis

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