Differential effects of hypothalamic long-chain fatty acid infusions on suppression of hepatic glucose production

R. A. Ross, L. Rossetti, T. K T Lam, Gary J. Schwartz

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61% from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg -1·min-1) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg -1·min-1 to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg-1·min-1). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume299
Issue number4
DOIs
StatePublished - Oct 2010

Fingerprint

Fatty Acids
Oleic Acid
Glucose
Hypothalamus
Liver
Palmitic Acid
Linoleic Acid
Insulin
Cerebral Ventricles
Monounsaturated Fatty Acids
Third Ventricle
Unsaturated Fatty Acids
Hypoglycemia

Keywords

  • Central nervous system
  • Diabetes
  • Nutrient sensing
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

@article{6e599104aab5461fa27e9e4df05495ef,
title = "Differential effects of hypothalamic long-chain fatty acid infusions on suppression of hepatic glucose production",
abstract = "Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61{\%} from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg -1·min-1) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg -1·min-1 to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg-1·min-1). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.",
keywords = "Central nervous system, Diabetes, Nutrient sensing, Obesity",
author = "Ross, {R. A.} and L. Rossetti and Lam, {T. K T} and Schwartz, {Gary J.}",
year = "2010",
month = "10",
doi = "10.1152/ajpendo.00190.2010",
language = "English (US)",
volume = "299",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Differential effects of hypothalamic long-chain fatty acid infusions on suppression of hepatic glucose production

AU - Ross, R. A.

AU - Rossetti, L.

AU - Lam, T. K T

AU - Schwartz, Gary J.

PY - 2010/10

Y1 - 2010/10

N2 - Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61% from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg -1·min-1) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg -1·min-1 to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg-1·min-1). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.

AB - Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61% from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg -1·min-1) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg -1·min-1 to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg-1·min-1). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.

KW - Central nervous system

KW - Diabetes

KW - Nutrient sensing

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=77957550128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957550128&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00190.2010

DO - 10.1152/ajpendo.00190.2010

M3 - Article

C2 - 20647558

AN - SCOPUS:77957550128

VL - 299

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 4

ER -