Group 1B phospholipase A₂ inactivation suppresses atherosclerosis and metabolic diseases in LDL receptor-deficient

Norris I Hollie1, Eddy S Konaniah1, Colleen Goodin1

  • 1Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.

Atherosclerosis
|April 22, 2014
PubMed
Abstract

Insights

Inactivating group 1B phospholipase A2 (Pla2g1b) prevents diet-induced obesity, diabetes, and atherosclerosis in mice. This suggests targeting Pla2g1b may reduce these conditions in humans.

Area of Science:

  • Biochemistry
  • Metabolic Diseases
  • Cardiovascular Research

Background:

  • Group 1B phospholipase A2 (Pla2g1b) inactivation is known to mitigate diet-induced metabolic dysfunction in C57BL/6 mice.
  • The impact of Pla2g1b inactivation on atherosclerosis has not been previously investigated.

Purpose of the Study:

  • To evaluate the efficacy of Pla2g1b inactivation in preventing atherosclerosis in a preclinical model.
  • To assess the role of Pla2g1b in diet-induced obesity, hyperglycemia, and hyperlipidemia.

Main Methods:

  • Utilized LDL receptor-deficient (Ldlr(-/-)) mice, exhibiting human-like hyperlipidemia.
  • Administered a hypercaloric diet (58.5% fat, 25% sucrose) for 10 weeks.
  • Compared atherosclerosis development and metabolic markers between Pla2g1b(+/+)Ldlr(-/-) and Pla2g1b(-/-)Ldlr(-/-) mice.

Main Results:

  • Pla2g1b(-/-)Ldlr(-/-) mice were resistant to diet-induced body weight gain.
  • These mice showed significantly lower fasting glucose, insulin, and plasma lipid levels.
  • Atherosclerotic lesions in the aortic roots were reduced seven-fold in Pla2g1b(-/-)Ldlr(-/-) mice.

Conclusions:

  • Pla2g1b inactivation effectively suppresses diet-induced obesity, diabetes, and atherosclerosis in Ldlr(-/-) mice.
  • Pharmacological inhibition of Pla2g1b presents a potential therapeutic strategy for reducing obesity and associated risks in humans.

Related Concept Videos

Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
2.5K
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
741
Inflammation01:38

Inflammation

Overview
46.6K
Lipid-derived Compounds in the Human Body01:31

Lipid-derived Compounds in the Human Body

Fats and lipids are crucial components in the human body. Some lipid-derived compounds, such as fat-soluble vitamins, eicosanoids, lipoproteins, and glycolipids, also play unique roles to support various  biological processes .
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
5.5K
Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.7K
Blood Studies for Cardiovascular System III: Serum Lipid Profile01:25

Blood Studies for Cardiovascular System III: Serum Lipid Profile

Understanding serum lipids is crucial for maintaining cardiovascular health and preventing heart disease and stroke.
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
854