The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-07

AUTHORS

M. Kusunoki, T. Hara, K Tsutsumi, T. Nakamura, T Miyata, F. Sakakibara, S. Sakamoto, H. Ogawa, Y. Nakaya, L. H. Storlien

ABSTRACT

Aims/hypothesis. 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 · kg–1· 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 whole-body insulin resistance (clamp glucose infusion rate: 4.8 ± 1.3 mg · kg–1· 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.¶Conclusion/interpretation: Lipoprotein lipase activators could have potential benefits for the treatment of obesity by increasing fat utilisation. [Diabetologia (2000) 43: 875–880] More... »

PAGES

875-880

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s001250051464

DOI

http://dx.doi.org/10.1007/s001250051464

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000551060

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10952460


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