Sohet, Florence
[UCL]
(eng)
Oxidative stress is often related to metabolic alterations occurring in diverse tissues upon obesity development and its associated disorders. The liver plays a key role in the maintenance of the body’s lipid and glucose homeostasis and is particularly sensitive to changes in the oxidative balance. Such changes might contribute to the occurrence of inflammatory processes and metabolic stresses in affected living organisms. Coenzyme Q is an effective lipid soluble antioxidant, which counteracts lipid peroxidation, directly or through the restoration of vitamin E. It also interacts with superoxide anions or other reactive oxygen species.
The aim of this work was to analyze the inflammatory, oxidative and metabolic stresses in diverse models of obesity and its associated disorders in order to better understand the potential role of lipid peroxidation in that context. The relevance of a nutritional supplementation with coenzyme Q was assessed in the control of certain metabolic alterations occurring upon obesity.
Experimental work was first conducted in normal mice fed a control diet, and thereafter, in several models of diabetes, inflammation and obesity, including models associated with a high-fat diet feeding of the animals, with a main focus on the liver.
One of the key conclusions of this work is that lipid peroxidation is not a prerequisite for the development of obesity and its associated metabolic disorders. Indeed, protection of tissue lipid peroxidation with high vitamin E levels does not interfere with the development of obesity or glucose intolerance upon a high-fat diet feeding of mice. Modulation of the high-fat diet by decreasing the vitamin E levels, by supplementing it with fructose or with thermally oxidized fat lead to diverse metabolic alterations such as increased lipid peroxidation (upon decreased vitamin E levels in the high-fat diet), increased inflammatory stresses (upon fructose supplementation) or modulated hepatic lipid content and metabolism that could be associated with the activation of the liver X receptor pathway (upon thermally oxidized fat supplementation).
Another interesting finding of this work is the potential anti-inflammatory properties of coenzyme Q. A trend of decreased inflammatory score and similar tendencies in several pro-inflammatory genes expression were highlighted following coenzyme Q supplementation in a model of obesity associated with chronic low grade inflammation induced by high-fat feeding and fructose consumption. An activation of NADPH oxidase could be a key point in the development of the chronic low-grade inflammation, being at the cross-roads between oxidative stress and inflammation.
Modulation of gut microbiota upon coenzyme Q supplementation has been highlighted in two different studies (increased Bacteroides in ob/ob mice and decreased Lactobacillus in high-fat fed mice supplemented with thermally oxidized fat). This could serve as a proof of concept that CoQ could modulate gut microbiota.
In conclusion, our data suggest that CoQ is really efficient in counteracting lipid peroxidation in the diet, but is not able to improve most of the metabolic alterations occurring upon high-fat diet feeding. However, its anti-inflammatory properties, as well as its mitochondrial-related effects, would be interesting to study in diverse patho-physiological contexts.
Bibliographic reference |
Sohet, Florence. Is lipid peroxidation involved in the metabolic alterations associated with obesity ?The use of coenzyme Q10 as a nutritional tool. Prom. : Delzenne, Nathalie |
Permanent URL |
http://hdl.handle.net/2078.1/76585 |