Related Experiment Video

Updated: Jun 13, 2026

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
07:46

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation

Published on: April 3, 2017

Macrophage fatty-acid synthase deficiency decreases diet-induced atherosclerosis

Jochen G Schneider1, Zhen Yang, Manu V Chakravarthy

  • 1Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The Journal of Biological Chemistry
|May 19, 2010
PubMed

Insights

Inactivating fatty-acid synthase (FAS) in macrophages reduces atherosclerosis by increasing liver X receptor alpha (LXRalpha). This suggests FAS plays a role in regulating cholesterol efflux and lesion development.

Area of Science:

  • Cardiovascular Biology
  • Metabolic Disease Research
  • Macrophage Biology

Background:

  • Fatty acid metabolism alterations are observed in atherosclerotic lesions.
  • The specific role of fatty acid synthesis in atherosclerosis development remains unclear.

Purpose of the Study:

  • To investigate the impact of fatty-acid synthase (FAS) inactivation in macrophages on atherosclerosis progression in apoE-deficient mice.

Main Methods:

  • Generated mice with fatty-acid synthase (FAS) knocked out in macrophages (FASKOM) using apoE-deficient background.
  • Assessed serum lipids, body weight, glucose metabolism, and blood pressure.
  • Quantified atherosclerotic lesion extent and foam cell formation.
  • Analyzed gene expression of nuclear receptors (LXRalpha, PPARalpha) and related targets (Abca1, CD36).
  • Performed bone marrow transplantation experiments with LXRalpha-deficient/FAS-deficient and LXRalpha-replete/FAS-deficient conditions.

Main Results:

  • FASKOM mice exhibited reduced atherosclerotic extent (20-40%) and diminished foam cell formation compared to controls.
  • Macrophage-specific FAS deficiency led to increased apoAI-specific cholesterol efflux and decreased oxidized LDL uptake.
  • Upregulation of liver X receptor alpha (LXRalpha) and its target Abca1, with downregulation of CD36, was observed in FASKOM macrophages.
  • PPARalpha target gene expression was decreased in FASKOM macrophages, but normalized with PPARalpha agonist treatment.
  • Bone marrow transplantation studies indicated anti-atherogenic effects of LXRalpha in the context of FAS deficiency.

Conclusions:

  • Macrophage fatty-acid synthase (FAS) deficiency confers protection against atherosclerosis.
  • This protection is mediated by the induction of liver X receptor alpha (LXRalpha), enhancing cholesterol efflux and reducing lipid uptake.
  • FAS, induced by LXRalpha, may produce regulatory lipids that feedback inhibit LXRalpha activity in macrophages, highlighting a novel regulatory loop in atherosclerosis.

More Related Videos

Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death08:26

Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death

Published on: October 31, 2017

Related Concept Videos

Inflammation01:38

Inflammation

Overview
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...
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...
Overview of Lipid Metabolism01:24

Overview of Lipid Metabolism

Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...