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Research article2017Peer reviewedOpen access

Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves glucose control in obese Zucker rats

Kroon, Tobias; Baccega, Tania; Olsen, Arne; Gabrielsson, Johan; Oakes, Nicholas D.

Abstract

Nicotinic acid (NiAc) is a potent inhibitor of lipolysis, acutely reducing plasma free fatty acid (FFA) concentrations. However, a major FFA rebound is seen during rapid NiAc washout, and sustained exposure is associated with tolerance development, with FFAs returning to pretreatment levels. Our aim was to find a rational NiAc dosing regimen that preserves FFA lowering, sufficient to reverse nonadipose tissue lipid accumulation and improve metabolic control, in obese Zucker rats. We compared feeding-period versus fasting-period NiAc dosing for 5 days: 12 h subcutaneous infusion (programmable, implantable mini-pumps) terminated by gradual withdrawal. It was found that NiAc timed to feeding decreased triglycerides in liver (-47%; P < 0.01) and heart (-38%; P < 0.05) and reduced plasma fructosamine versus vehicle. During oral glucose tolerance test, plasma FFA levels were reduced with amelioration of hyperglycemia and hypertriglyceridemia. Furthermore, timing NiAc to feeding resulted in a general downregulation of de novo lipogenesis (DNL) genes in liver. By contrast, NiAc timed to fasting did not reduce tissue lipids, ameliorate glucose intolerance or dyslipidemia, or alter hepatic DNL genes.(Jlr) In conclusion, NiAc dosing regimen has a major impact on metabolic control in obese Zucker rats. Specifically, a well-defined NiAc exposure, timed to feeding periods, profoundly improves the metabolic phenotype of this animal model.

Keywords

lipolysis and fatty acid metabolism; diabetes; insulin; adipose tissue; drug therapy/hypolipidemic drugs; niacin; GPR109A; liver

Published in

Journal of Lipid Research
2017, volume: 58, number: 1, pages: 31-41

SLU Authors

Associated SLU-program

Animal health (until May 2010)

Global goals (SDG)

SDG3 Good health and well-being

UKÄ Subject classification

Pharmaceutical Sciences

Publication identifier

  • DOI: https://doi.org/10.1194/jlr.M068395

Permanent link to this page (URI)

https://res.slu.se/id/publ/80101