Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

• Published in: Diabetologia Vol. 54; no. 10; pp. 2626 - 2638
• Main Authors: Flachs, P., Rühl, R., Hensler, M., Janovska, P., Zouhar, P., Kus, V., Macek Jilkova, Z., Papp, E., Kuda, O., Svobodova, M., Rossmeisl, M., Tsenov, G., Mohamed-Ali, V., Kopecky, J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-10-2011; Springer; Springer Nature B.V
• Subjects: Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Animals; Biological and medical sciences; Body fat; Caloric Restriction; Diabetes. Impaired glucose tolerance; Diet, High-Fat; Dietary Fats - pharmacology; Docosahexaenoic Acids - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism - drug effects; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acids, Omega-3 - pharmacology; Human Physiology; Immunohistochemistry; Insulin resistance; Internal Medicine; Lipid Metabolism - drug effects; Lipids; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolites; Mice; Mice, Obese; Miscellaneous; Obesity; Other metabolic disorders; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - metabolism; Real-Time Polymerase Chain Reaction; Hungary; Czech Republic; prostaglandin J; White adipose tissue; EPA; 15-Deoxy-Δ; DHA; Metabolic syndrome; Fish oil; Endocrinopathy; Cardiovascular disease; Lipids; n-3 fatty acid; Eicosanoid; Nutritional status; Obesity; Prostaglandin; Arachidonic acid derivatives; Diabetes mellitus; Rodentia; Nutrition disorder; Polyunsaturated fatty acid; Metabolic diseases; Edible oil; Vertebrata; Mammalia; Mouse; Animal; Unsaturated fatty acid; Catabolism
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2233-2

Aims/hypothesis
Calorie restriction is an essential component in the treatment of obesity and associated diseases. Long-chain
n-
3 polyunsaturated fatty acids (LC
n-
3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC
n-
3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice.
Methods
Male mice (C57BL/6J) were habituated to a corn-oil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC
n-
3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF + F), ad libitum; (3) cHF with calorie restriction (CR; cHF + CR); and (4) cHF + F + CR. Mice fed a chow diet were also studied.
Results
We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC
n-
3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ
12,15
-prostaglandin J
2
and protectin D1.
Conclusions/interpretation
White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC
n-
3 PUFA to improve therapeutic strategies for metabolic syndrome.