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Last update 08 May 2025

ANGPTL8

Last update 08 May 2025

Basic Info

Synonyms

angiopoietin like 8, Angiopoietin-like protein 8, ANGPTL8

+ [6]

Introduction

Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels (PubMed:22569073, PubMed:22809513, PubMed:23150577). May be involved in the metabolic transition between fasting and refeeding: required to direct fatty acids to adipose tissue for storage in the fed state (By similarity).

Drugs associated with ANGPTL8

ANGPTL8 siRNA(Eli Lilly)

Target

ANGPTL8

Mechanism

ANGPTL8 antagonists

Active Org.

Eli Lilly & Co.

Originator Org.

Eli Lilly & Co.

Active Indication

Nonalcoholic Steatohepatitis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WO2024138111

Patent Mining

Target

ANGPTL8

Mechanism-

Active Org.

Eli Lilly & Co.

Originator Org.

Eli Lilly & Co.

Active Indication

Cardiovascular Diseases [+3]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LY-3475766

Target

ANGPTL3 x ANGPTL8

Mechanism

ANGPTL3 inhibitors [+1]

Active Org.-

Originator Org.

Eli Lilly & Co.

Active Indication-

Inactive Indication

Dyslipidemias

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ANGPTL8

NCT04052594

/ CompletedPhase 1

A Randomized, Double-Blind, Single Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3475766

This study will evaluate the safety and tolerability of LY3475766 when given to participants with high levels of blood fat called triglycerides. It will also investigate how the body processes the study drug and the effect of the study drug on the body. Information about any side effects will be documented. This study will last up to 16 weeks for each participant.

Start Date03 Sep 2019

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with ANGPTL8

100 Translational Medicine associated with ANGPTL8

0 Patents (Medical) associated with ANGPTL8

479

Literatures (Medical) associated with ANGPTL8

21 Apr 2025·Endocrine, Metabolic & Immune Disorders - Drug Targets

Evaluation of Betatrophin, Chemerin, and Kisspeptin Levels in Acromegaly Patients

Article

Author: Avci, Esin ; Cayan, Dondu Aysegul ; Topsakal, Senay

Background:Acromegaly is a chronic disorder characterized by excessive growth hormone (GH) secretion from pituitary somatotroph cells, resulting in metabolic complications and increased morbidity. Elevated levels of GH and insulin-like growth factor 1 (IGF-1) contribute to various metabolic and morphological abnormalities. Betatrophin, produced in the liver and adipose tissue, plays a significant role in regulating glucose and lipid metabolism. Chemerin, an adipokine, influences insulin sensitivity, lipid metabolism, and inflammation. Additionally, kisspeptin, a neuropeptide, stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) through the hypothalamic-pituitary-gonadal axis.Objective:This study aimed to investigate the levels of betatrophin, chemerin, and kisspeptin in acromegaly patients and their potential relationship with dyslipidemia and diabetes.Methods:This study included 40 patients diagnosed with acromegaly and 40 healthy controls. GH and IGF-1 levels were measured, and venous blood samples were analyzed for betatrophin, chemerin, and kisspeptin levels using ELISA.Results:The analysis revealed no significant difference in betatrophin levels between acromegaly patients and controls (p>0.05). However, significantly lower levels of chemerin and kisspeptin were observed in patients with acromegaly (p<0.001). Furthermore, a significant correlation was identified between IGF-1 and kisspeptin levels, indicating a potential pathway for future research in diagnostics and therapy.Conclusion:This study highlights the altered levels of chemerin and kisspeptin in acromegaly patients, suggesting their involvement in metabolic dysregulation associated with the condition. Further investigation into the correlation between IGF-1 and kisspeptin could provide insights into developing targeted therapeutic strategies.

01 Apr 2025·Cell Death & Differentiation

Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates

Article

Author: You, Hui-Juan ; Xu, Li ; Huang, Kun ; Zheng, Ling ; Hu, De-Sheng ; Xiao, Yu-Shuo ; Zhou, Yi-Hao ; Wan, Shi-Yuan ; Petersen, Robert B ; Zhang, Yong-Hui ; Xie, Yun-Hao ; Liu, Xin-Ran ; Wan, Jun ; Song, Qiu-Yi ; Zhang, Zi-Tong ; Chen, Hong ; Li, Xi ; Zhang, Yu ; Yang, Jing

Upon genotoxic stresses, cells employ various DNA damage responses (DDRs), including DNA damage repair or apoptosis, to safeguard genome integrity. However, the determinants among different DDRs choices are largely unknown. Here, we report angiopoietin-like protein 8 (ANGPTL8), a secreted regulator of lipid metabolism, localizes to the nucleus and acts as a dynamic switch that directs DDRs towards apoptosis rather than DNA repair after genotoxin exposure. ANGPTL8 deficiency alleviates DNA damage and apoptosis in cells exposed to genotoxins, as well as in the liver or kidney of mice injured by hepatic ischemia/reperfusion or cisplatin treatment. Mechanistically, ANGPTL8 physically interacts with Poly (ADP-ribose) polymerase 1 (PARP1), in a PARylation-independent manner, and reduces the fluidity of PARP1-DNA condensates, thereby enhancing the pro-apoptotic accumulation of PARP1 and PAR chains on DNA lesions. However, the transcription of ANGPTL8 is gradually decreased following genotoxin treatment, partly due to downregulation of CCAAT enhancer binding protein alpha (CEBPA), presumably to avoid further cytotoxicity. Together, we provide new insights by which genotoxic stress induced DDRs are channeled to suicidal apoptosis to safeguard genome integrity.

01 Apr 2025·Domestic Animal Endocrinology

Alterations in serum concentrations of visfatin and betatrophin in dogs with diabetes mellitus

Article

Author: Mazaki-Tovi, Michal ; Slon, Alexandra

Canine diabetes mellitus (DM) is associated with hyperglycemia and hyperlipidemia. Visfatin and betatrophin are adipokines involved in the pathophysiology of insulin resistance and deranged lipid metabolism, and are also altered in obesity. We hypothesized that visfatin and betatrophin serum concentrations are altered in diabetic dogs, irrespective of their body condition. The study included 23 newly-diagnosed DM (NDDM) dogs, 34 insulin-treated DM (ITDM) dogs and 24 healthy dogs. Body condition score was determined and fasted serum samples were collected for measurement of betatrophin, visfatin and insulin serum concentrations. Visfatin concentrations (mean, 95% CI) were lower in overweight NDDM (4.5 ng/mL, 2.5-8.1, P=0.05) and ITDM (2.8 ng/mL 1.8-4.3, P=0.006) than healthy (7.7 ng/mL, 5.0-11.7) dogs, but were not different among lean dogs, and were negatively correlated to betahydroxybutyric acid in ITDM dogs (r=-0.59, P=0.05). Betatrophin concentrations were lower in NDDM (69 pg/mL, 43-112, P<0.001) and ITDM (53 pg/mL, 34-84, P<0.001) than healthy (267 pg/mL, 167-426) dogs. Among NDDM dogs, betatrophin concentrations were higher in those with concurrent liver disease (203 pg/mL, 49-844) than those with no evidence of liver disease (19 pg/mL, 4-90, P=0.007), and were negatively correlated with glucose concentrations (r=-0.44, P=0.04) and creatinine (r=-0.60, P=0.003). Insulin concentrations were not different among NDDM and healthy dogs. Among NDDM dogs, insulin concentrations were negatively correlated to concentrations of betahydroxybutyric acid (r=-0.65, P=0.002) and were lower in dogs with concurrent kidney disease (5.6 mU/L, 2.1-15.3) compared to those with no evidence of kidney disease (20.6 mU/L, 8.0-53.2, P=0.018). In conclusion, DM in dogs is associated with alteration in visfatin and betatrophin concentrations that are not resolved by insulin treatment.

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ANGPTL8

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