Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding

Katie C. Coate, Guillaume Kraft, Mary Courtney Moore, Marta S. Smith, Christopher Ramnanan, Jose M. Irimia, Peter Roach, Ben Farmer, Doss W. Neal, Phil Williams, Alan D. Cherrington

Research output: Contribution to journalArticle

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Abstract

In dogs consuming a high-fat and -fructose diet (52 and 17% of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity. The present study compared the impact of selective increases in dietary fat and fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before undergoing clamp studies with infusion of somatostatin and intraportal insulin (3-4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min (P1) and portal vein (4 mg·kg-1·min-1) plus Pe glucose infusion during the final 90 min (P2). During P2, HGU was 2.8 ± 0.2, 1.0 ± 0.2, and 0.8 ± 0.2 mg·kg-1·min-1 in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were reduced (P < 0.05) 35 and 56%, respectively, in HFA, and 53 and 74%, respectively, in HFR. Liver glycogen concentrations were 20 and 38% lower in HFA and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05) in HFA (21%) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects were not additive, suggesting that they act via the same mechanism or their effects converge at a saturable step.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2014

Fingerprint

Fructose
Fats
Glucose
Liver
Glucokinase
Liver Glycogen
Dogs
Insulin
Diet
Glycogen Synthase
Dietary Fats
Hyperinsulinism
High Fat Diet
Portal Vein
Somatostatin
Glucagon
Hyperglycemia
Veins
Proteins
Phosphorylation

Keywords

  • Glucokinase
  • Glycogen
  • Glycogen phosphorylase
  • Glycogen synthase
  • Insulin signaling

ASJC Scopus subject areas

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

Cite this

Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding. / Coate, Katie C.; Kraft, Guillaume; Moore, Mary Courtney; Smith, Marta S.; Ramnanan, Christopher; Irimia, Jose M.; Roach, Peter; Farmer, Ben; Neal, Doss W.; Williams, Phil; Cherrington, Alan D.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 307, No. 2, 15.07.2014.

Research output: Contribution to journalArticle

Coate, KC, Kraft, G, Moore, MC, Smith, MS, Ramnanan, C, Irimia, JM, Roach, P, Farmer, B, Neal, DW, Williams, P & Cherrington, AD 2014, 'Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding', American Journal of Physiology - Endocrinology and Metabolism, vol. 307, no. 2. https://doi.org/10.1152/ajpendo.00083.2014
Coate, Katie C. ; Kraft, Guillaume ; Moore, Mary Courtney ; Smith, Marta S. ; Ramnanan, Christopher ; Irimia, Jose M. ; Roach, Peter ; Farmer, Ben ; Neal, Doss W. ; Williams, Phil ; Cherrington, Alan D. / Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding. In: American Journal of Physiology - Endocrinology and Metabolism. 2014 ; Vol. 307, No. 2.
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abstract = "In dogs consuming a high-fat and -fructose diet (52 and 17{\%} of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity. The present study compared the impact of selective increases in dietary fat and fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before undergoing clamp studies with infusion of somatostatin and intraportal insulin (3-4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min (P1) and portal vein (4 mg·kg-1·min-1) plus Pe glucose infusion during the final 90 min (P2). During P2, HGU was 2.8 ± 0.2, 1.0 ± 0.2, and 0.8 ± 0.2 mg·kg-1·min-1 in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were reduced (P < 0.05) 35 and 56{\%}, respectively, in HFA, and 53 and 74{\%}, respectively, in HFR. Liver glycogen concentrations were 20 and 38{\%} lower in HFA and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05) in HFA (21{\%}) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects were not additive, suggesting that they act via the same mechanism or their effects converge at a saturable step.",
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AU - Ramnanan, Christopher

AU - Irimia, Jose M.

AU - Roach, Peter

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N2 - In dogs consuming a high-fat and -fructose diet (52 and 17% of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity. The present study compared the impact of selective increases in dietary fat and fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before undergoing clamp studies with infusion of somatostatin and intraportal insulin (3-4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min (P1) and portal vein (4 mg·kg-1·min-1) plus Pe glucose infusion during the final 90 min (P2). During P2, HGU was 2.8 ± 0.2, 1.0 ± 0.2, and 0.8 ± 0.2 mg·kg-1·min-1 in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were reduced (P < 0.05) 35 and 56%, respectively, in HFA, and 53 and 74%, respectively, in HFR. Liver glycogen concentrations were 20 and 38% lower in HFA and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05) in HFA (21%) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects were not additive, suggesting that they act via the same mechanism or their effects converge at a saturable step.

AB - In dogs consuming a high-fat and -fructose diet (52 and 17% of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity. The present study compared the impact of selective increases in dietary fat and fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before undergoing clamp studies with infusion of somatostatin and intraportal insulin (3-4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min (P1) and portal vein (4 mg·kg-1·min-1) plus Pe glucose infusion during the final 90 min (P2). During P2, HGU was 2.8 ± 0.2, 1.0 ± 0.2, and 0.8 ± 0.2 mg·kg-1·min-1 in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were reduced (P < 0.05) 35 and 56%, respectively, in HFA, and 53 and 74%, respectively, in HFR. Liver glycogen concentrations were 20 and 38% lower in HFA and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05) in HFA (21%) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects were not additive, suggesting that they act via the same mechanism or their effects converge at a saturable step.

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