The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet.
OBJECTIVE
Fat balance is critical in the aetiology of obesity and related diseases. Lipoprotein lipase is of major importance in lipid metabolism. The aim of this study was to investigate the long-term effects of the lipoprotein lipase activator, NO-1886, on substrate utilisation, adiposity and insulin action in rats fed a high-fat diet.


METHODS
Male, Sprague-Dawley rats were fed for 10 weeks on a chow diet or a high-fat diet with, or without, NO-1886 (50 mg x kg(-1) x day(-1)). Weight gain, fat accumulation and both hormone-sensitive and lipoprotein, lipase activities were measured. Insulin action was assessed by the euglycaemic hyperinsulinaemic clamp and metabolic rate/substrate utilisation by open-circuit respirometry.


RESULTS
Compared with chow-fed controls, a high-fat diet increased weight gain, an effect lessened by NO-1886 [weight gain (g): chow, 37 +/- 3, high-fat, 222 +/- 9; high-fat + NO-1886, 109 +/- 6, all groups differed p < 0.001]. A similar pattern existed for fat accumulation [visceral fat (g): chow, 35.9 +/- 3.2; high-fat, 81.9 +/- 6.6; high-fat + NO-1886, 52.3 +/- 4.7, p < 0.01 high-fat vs the other groups]. A high-fat diet induced wholebody insulin resistance (clamp glucose infusion rate: 4.8 +/- 1.3 mg x kg(-1) x min(-1) vs 10.6 +/- 1.1 for the chow group, p < 0.01) with NO-1886 lessening this effect (8.3 +/- 0.5, p < 0.05 vs high-fat). The 24-h respiratory quotient was lower in the high-fat + NO-1886 group (0.825 +/- 0.010) compared with high-fat alone (0.849 +/- 0.004, p < 0.05). A high-fat diet increased lipoprotein and hormone-sensitive, lipase activities in epididymal fat, an effect not altered by NO-1886. In myocardium and skeletal muscle a high-fat diet lowered lipoprotein lipase activity, an effect lessened by NO-1886.


CONCLUSIONS
Lipoprotein lipase activators could have potential benefits for the treatment of obesity by increasing fat utilisation.
Kusunoki
M
M
The First Department of Internal Medicine, Aichi Medical University, Aichi-gun, Japan.
Hara
T
T
Tsutsumi
K
K
Nakamura
T
T
Miyata
T
T
Sakakibara
F
F
Sakamoto
S
S
Ogawa
H
H
Nakaya
Y
Y
Storlien
L H
LH
D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D001549:Benzamides; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D009943:Organophosphorus Compounds; D014280:Triglycerides; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D008071:Lipoprotein Lipase