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.”

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.

Related articles

Reimagining STEM workforce development as a braided river
Rebecca L. Batchelor, Hendratta Ali, Kathryn G. Gardner-Vandy, Anne U. Gold, Jennifer A. MacKinnon & Pranoti M. Asher

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

St. Jude and maximizing the value of blood
Health Observance

St. Jude and maximizing the value of blood

June 14, 2021

The hospital is most renowned for passing along no costs to families. To facilitate this, the in-house capabilities of St. Jude are second to none. This includes the on-site blood donation facilities.

A balancing game with implications for neurodegenerative disease
Journal News

A balancing game with implications for neurodegenerative disease

June 8, 2021

The relationship between two proteins, one essential to mitochondrial fission and the other found in Alzheimer’s tissue, might hold the key to how disease alters the fission–fusion balance.

Can people vaccinated against COVID-19 still spread the coronavirus?
News

Can people vaccinated against COVID-19 still spread the coronavirus?

June 6, 2021

Preliminary evidence seems to suggest that someone who’s vaccinated is less likely transmit the virus, but the proof is not yet ironclad.

Addgene expands its collection into antibodies
News

Addgene expands its collection into antibodies

June 4, 2021

The reagent repository Addgene, known for distribution and quality control of plasmids for open science, is expanding into recombinant antibodies and nanobodies in partnership with NeuroMab.

Study reveals experimental targets for lymphoma research
Journal News

Study reveals experimental targets for lymphoma research

June 3, 2021

An enzyme previously linked to lymphoma development may have more functions than previously thought.

Exploring underappreciated molecules and new cities
Interview

Exploring underappreciated molecules and new cities

June 2, 2021

Neurochemist Xianlin Han has been an associate editor for the Journal of Lipid Research since 2019.