Journal News

ANGPTL3: A promising therapeutic direction for cardiovascular disease

Gelareh (Abulwerdi)  Vinueza
March 17, 2020

Despite major advances in the treatment of cardiovascular disease, or CVD, with statins, antihypertensive and antithrombotic drugs, a residual number of patients with CVD remain untreated. These patients have a genetic disorder or extremely high levels of triglycerides (hypertriglyceridemia) that render them unresponsive to current therapies. To find new therapies, researchers are targeting circulating lipids and lipoproteins. A sedentary lifestyle and a diet high in sugar, fat and processed carbohydrates increase a person’s risk of developing CVD.

obese_rhesus_400x251.jpg
Courtesy of Peter Havel
Adult male rhesus macaques were fed an unrestricted diet and water along
with a flavored 15% fructose solution and then treated with fish oil
supplements to demonstrate the role of diet on ANGPTL3 protein levels.

Two main sugars in the human diet are glucose and fructose. Glucose, the major component of dietary carbohydrates, is a product of starch. Fructose is found mainly in soft drinks and other beverages, desserts and candies. Although similar in calories, glucose and fructose are metabolized differently. Glucose is absorbed rapidly by almost all cells in the body, and its levels remain balanced through insulin release. Fructose is metabolized mainly by the liver, and its levels are not regulated by insulin; increased fructose consumption increases circulating triglycerides, low-density lipoprotein cholesterol, and fat around organs and blood vessels. In the process of de novo lipogenesis, fructose in the liver metabolizes to lipids.

The liver expresses and secretes angiopoietinlike 3, or ANGPTL3, which plays a role in lipid clearance; therefore, scientists see this protein as a promising therapeutic target for developing lipid-lowering drugs that target formation of triglycerides. In a recent paper in the Journal of Lipid Research, Peter Havel and colleagues wrote that consumption of dietary fructose increases circulating levels of ANGPTL3 in rhesus macaques by 30% to 40%. Increased ANGPTL3 correlated with increased levels of plasma triglycerides.

In collaboration with Arrowhead Pharmaceuticals, the authors found that inhibiting hepatic ANGPTL3 expression using RNA interference technology resulted in reduced circulating ANGPTL3 and triglycerides in rhesus macaques. Supplementing the macaques’ diet with fish oil led to decreased levels of ANGPTL3.

“These are the first studies to demonstrate the effect of diet (fructose and omega-3 fatty acids in fish oil) on ANGPTL3,” Havel said, “and suggest that ANGPTL3 is a promising target for management of hypertriglyceridemia.”

The role of dietary sugars in metabolism is a focus of Havel’s lab at the University of California, and the researchers have developed the rhesus macaque model of metabolic syndrome “in which consuming sugar-sweetened beverages accelerates the development of insulin resistance and dysregulation of lipid metabolism,” he said.

For patients with CVD who can’t benefit from current treatments, this research opens exciting possibilities for new therapies. “Suppression of ANGPTL3 production may be an important mechanism,” Havel said. “Fish oil supplements, when consumed in adequate amounts, lower plasma triglycerides and reduces CVD risk.”

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition monthly.

Learn more
Gelareh (Abulwerdi)  Vinueza

Gelareh (Abulwerdi) Vinueza graduated with her Ph.D. from the molecular medicine program at the University of Maryland, Baltimore. She is currently a policy fellow at the Food and Drug Administration. She has been an ASBMB volunteer writer since 2018 and is passionate about science communication and science policy. Outside of work, she enjoys photography, hiking and cooking.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Mapping the placenta’s hormone network
Journal News

Mapping the placenta’s hormone network

Oct. 21, 2025

Study uncovers how the placenta actively metabolizes not only glucocorticoids but also novel androgens and progesterones, reshaping our understanding of pregnancy and its complications.

Biochemists and molecular biologists sweep major 2025 honors
News

Biochemists and molecular biologists sweep major 2025 honors

Oct. 20, 2025

Recent Nobel, MacArthur and Kimberly Prize honorees highlight the power of biochemistry and molecular biology to drive discovery, including immune tolerance, vaccine design and metabolic disease, and to advance medicine and improve human health.

Spider-like proteins spin defenses to control immunity
News

Spider-like proteins spin defenses to control immunity

Oct. 17, 2025

Researchers from Utrecht University discovered two distinct binding modes of a spider-shaped immune inhibitor found in serum.

A biological camera: How AI is transforming retinal imaging
Feature

A biological camera: How AI is transforming retinal imaging

Oct. 15, 2025

AI is helping clinicians see a more detailed view into the eye, allowing them to detect diabetic retinopathy earlier and expand access through tele-ophthalmology. These advances could help millions see a clearer future.

AI in the lab: The power of smarter questions
Essay

AI in the lab: The power of smarter questions

Oct. 14, 2025

An assistant professor discusses AI's evolution from a buzzword to a trusted research partner. It helps streamline reviews, troubleshoot code, save time and spark ideas, but its success relies on combining AI with expertise and critical thinking.

Training AI to uncover novel antimicrobials
Feature

Training AI to uncover novel antimicrobials

Oct. 9, 2025

Antibiotic resistance kills millions, but César de la Fuente’s lab is fighting back. By pairing AI with human insight, researchers are uncovering hidden antimicrobial peptides across the tree of life with a 93% success rate against deadly pathogens.