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Human and experimental septic shock are characterized by depletion of lipid droplets in the adrenals.

Summary of "Human and experimental septic shock are characterized by depletion of lipid droplets in the adrenals."


RATIONALE:
Cholesteryl ester deficiency which results in adrenal lipid store depletion has been proposed as a potential mechanism of sepsis associated adrenal insufficiency.
OBJECTIVE:
We investigated histological abnormalities associated with sepsis in human and mice adrenals.
METHODS:
From January 2006 to 2008, seven patients who died of septic shock and seven patients with rapidly fatal nonseptic illness were included. Adrenals were sampled within 12 h from death. Adrenals were also taken from 13 lipopolysaccharide (LPS)-challenged mice, 5 cecal ligation and puncture (CLP) mice and 5 controls. We semi-quantitatively analysed intensity of inflammation, necrosis, haemorrhage and lipid depletion. MEASUREMENTS AND MAIN
RESULTS:
In patients, lipid depletion scores were significantly higher in septic shock than in controls (p = 0.011). In animals, lipid depletion was higher following LPS or CLP than in controls (p = 0.003). In adrenal cortex, in patients and not in animals, global scores for inflammation (p = 0.002), necrosis (p = 0.009) and haemorrhage (p = 0.009) were significantly higher in septic shock than in controls. Similarly, in zona fasciculata, in patients and not in animals, scores for inflammation (p = 0.007), necrosis (p = 0.023) and haemorrhage (p = 0.023) were significantly higher in septic shock than in controls.
CONCLUSIONS:
This study shows that diffuse lipid depletion in zona fasciculata is a hallmark of human septic shock, experimental endotoxaemia and sepsis. In patients, sepsis was associated with inflammation, necrosis and haemorrhage predominantly in zona fasciculata.

Affiliation

General Intensive Care Unit and Laboratoire d'étude de la réponse neuroendocrine au sepsis EA4342, Service de Réanimation, Raymond Poincaré Hospital (AP-HP), University Versailles Saint-Quentin en Yvelines, 92380, Garches, France.

Journal Details

This article was published in the following journal.

Name: Intensive care medicine
ISSN: 1432-1238
Pages:

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A perilipin that is expressed by many different cell types. It binds FATTY ACIDS and CHOLESTEROL, stabilizes TRIGLYCERIDES, and localizes to both the surface and hydrophobic core of LIPID DROPLETS, as well as the ENDOPLASMIC RECTICULUM and PLASMA MEMBRANE in MACROPHAGES. It also plays a central role in the biogenesis of lipid droplets and FOAM CELLS and is highly expressed by macrophages at atherosclerotic lesions in human arteries along with the INFLAMMATION markers TNF-ALPHA; MCP-1 RECEPTOR; and IL-6.

A perilipin that localizes to LIPID DROPLETS; CYTOPLASM; ENDOSOMES; and PLASMA MEMBRANE, especially in MACROPHAGES. It functions as a transporter of free fatty acids to lipid droplets to promote their biogenesis and growth. It is also required for the transport of the MANNOSE-6-PHOSPHATE RECEPTOR from endosomes to the TRANS-GOLGI NETWORK. Its structure consists of four helix bundles that interact with the hydrophobic lipid droplet surface.

A perilipin protein characterized by an extensive 11-mer repeat region, which forms five adjacent alpha-helices. It is expressed primarily in WHITE ADIPOSE TISSUE and differentiating ADIPOCYTES, as well as skeletal muscle and heart. It is soluble in the cytoplasm but re-localizes to the surface of LIPID DROPLETS under high lipid conditions.

Proteins, such as PERILIPINS, that localize to LIPID DROPLETS either transiently or constitutively.

Dynamic cytoplasmic organelles found in almost all cells. They consist of a central core of LIPIDS surrounded by a phospholipid monolayer studded with surface proteins, and are involved in LIPID METABOLISM and storage.

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