Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids.
OBJECTIVE
Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids (PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue.


METHODS
Male obese diabetic (db/db) mice were treated with either a low-fat standard diet (LF), or high-fat diets rich in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) or the latter including marine n-3 PUFA (HF/3). White adipose tissue was analyzed for gene expression, fatty acid composition and by immunofluorescence.


RESULTS
HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes.


CONCLUSIONS
N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients.
Huber
J
J
Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria.
Löffler
M
M
Bilban
M
M
Reimers
M
M
Kadl
A
A
Todoric
J
J
Zeyda
M
M
Geyeregger
R
R
Schreiner
M
M
Weichhart
T
T
Leitinger
N
N
Waldhäusl
W
W
Stulnig
T M
TM
D017667:Adipocytes / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002403:Cathepsins / Q000235:genetics; D048429:Cell Size; D017364:Collagenases / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000008:administration & dosage / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000502:physiology; D006066:Gonads / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D014280:Triglycerides / Q000032:analysis
D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D019714:Tissue Inhibitor of Metalloproteinases; D014280:Triglycerides; D002403:Cathepsins; D017364:Collagenases; D053508:Matrix Metalloproteinase 12