Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of glucose production in women

Wei Wang, Alice Basinger, Richard A. Neese, Mark Christiansen, Marc K. Hellerstein

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Chronic nicotinic acid (NA) ingestion effectively lowers lipid levels, but adverse effects on glucose metabolism have been reported. Our goal was to investigate acute and chronic effects of NA on lipolysis and glucose metabolism in women. Healthy normolipidemic volunteers (n = 5) were studied twice; four-day hospital stays were separated by 1 mo, during which time subjects took increasing doses of NA to 2 g/day (500 mg, 4 times). In the second study, 500 mg of NA was given at 0800. Rates of appearance (R(a)) of free fatty acid (FFA), glycerol, and glucose were determined by isotope dilution (of [1,2,3,4-13C4]-palmitate, [2-13C1]glycerol, and [U-13C6]glucose). Mass isotopomer distribution analysis was used to measure gluconeogenesis and glycogenolysis. Fasting FFA concentrations ([FFA]), R(a) FFA, and R(a) glycerol were nonsignificantly elevated after 1 mo. Acute NA induced a significant reduction followed by a rebound overshoot of [FFA], R(a) FFA, and R(a) glycerol. Whole body fat oxidation fell initially and then increased back to basal levels; endogenous glucose production (EGP) increased in parallel with carbohydrate oxidation and then returned to basal values. The increased EGP was due entirely to increased glycogenolysis, not gluconeogenesis. We conclude that chronic effects of NA on FFA metabolism are complex (acute suppression followed by overshoot of R(a) FFA and [FFA] on top of a trend toward basal elevations), that responses after NA are consistent with operation of a glucose-fatty acid cycle in peripheral tissues, and that secondary effects on EGP were through changes in glycogenolysis, not gluconeogenesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume279
Issue number1 42-1
StatePublished - 2000
Externally publishedYes

Keywords

  • Gluconeogenesis
  • Glycogenolysis
  • Lipolysis
  • Mass isotopomer distribution analysis
  • Randle cycle

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

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