Lipase maturation factor 1: its expression in Zucker diabetic rats, and effects of metformin and fenofibrate.
OBJECTIVE
High triglyceride (TG) levels are a risk factor for cardiovascular diseases, and TG concentrations depend on the balance between its appearance in and clearance from plasma. TG clearance is controlled mainly by lipoprotein lipase (LPL), the maturation and activity of which are dependent on lipase maturation factor 1 (LMF1) protein. The present study aimed to investigate LMF1 expression in hypertriglyceridaemia and the regulation of its expression, as little is currently known of these processes.


METHODS
We measured LMF1 expression (mRNA) in Zucker diabetic rats (ZDF) throughout the development of obesity, insulin resistance and diabetes, and compared it with that of control rats. We also determined whether fenofibrate and metformin, agents with TG-lowering activities, have an effect on LMF1 expression in ZDF rats.


RESULTS
At 7 weeks, the ZDF rats were obese, insulin-resistant and hypertriglyceridaemic, and their LMF1 mRNA levels were - whichever tissue was investigated - comparable to those of the control rats. Diabetic ZDF rats (14 and 21-week-old) also had high TG levels, but the presence of diabetes had no effect on LMF1 expression; mRNA levels remained comparable to those in the controls. Although fenofibrate and metformin both decreased plasma TG levels, fenofibrate had no effect on LMF1 expression, whereas metformin increased LMF1 mRNA in heart tissue (14- and 21-week-old ZDF rats; P<0.01), and induced a trend towards increases in adipose tissue (14-week-old ZDF rats) and muscle (14- and 21-week-old ZDF rats).


CONCLUSIONS
LMF1 expression was not altered in this experimental animal model of obesity, insulin resistance and diabetes in the presence of raised TG levels. However, metformin increased LMF1 expression in the heart, suggesting that stimulation of LMF1 may play a part in its TG-lowering action.
EA 4173-ERI 22 agressions vasculaires et réponses tissulaires, faculté Rockefeller, UCB Lyon-1, Lyon, France.
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Forcheron
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Basset
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Del Carmine
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Beylot
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005230:Fatty Acids, Nonesterified / Q000097:blood; D011345:Fenofibrate / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; C546367:LMF1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D008687:Metformin; D011345:Fenofibrate