Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes

Berry, Michael N.; Phillips, John W.; Henly, Debra C.; Clark, Dallas G.

doi:10.1016/0014-5793(93)80030-x

Cited by 26 publications

(40 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, overexpression of glucose transporter Slc2a1 in mouse cardiac tissue increases glucose uptake and oxidation while decreasing FAO, despite a high supply of fatty acids (Yan et al 2009). A relationship between FAO and glucose consumption and oxidation has also been reported in rat hepatocytes (Berry et al 1993), rat myocytes (Abdel-aleem et al 1994), rat skeletal muscle (Kaushik et al 2001), and rat (Saddik et al 1993, Lavrentyev et al 2004) and mouse cardiac tissues (Campbell et al 2002).…”

Section: Discussionmentioning

confidence: 96%

Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

Paczkowski¹,

Schoolcraft²,

Krisher³

2014

Reproduction

View full text Add to dashboard Cite

Fatty acid b-oxidation (FAO) is essential for oocyte maturation in mice. The objective of this study was to determine the effect of etomoxir (a FAO inhibitor; 100 mM), carnitine (1 mM), and palmitic acid (1 or 100 mM) during maturation on metabolism and gene expression of the oocyte and cumulus cells, and subsequent embryo development in the mouse. Carnitine significantly increased embryo development, while there was a decrease in development following maturation with 100 mM palmitic acid or etomoxir (P!0.05) treatment. Glucose consumption per cumulus-oocyte complex (COC) was decreased after treatment with carnitine and increased following etomoxir treatment (P!0.05). Intracellular oocyte lipid content was decreased after carnitine or etomoxir exposure (P!0.05). Abundance of Slc2a1 (Glut1) was increased after etomoxir treatment in the oocyte and cumulus cells (P!0.05), suggesting stimulation of glucose transport and potentially the glycolytic pathway for energy production when FAO is inhibited. Abundance of carnitine palmitoyltransferase 2 (Cpt2) tended to increase in oocytes (PZ0.1) after treatment with 100 mM palmitic acid and in cumulus cells after exposure to 1 mM palmitic acid (PZ0.07). Combined with carnitine, 1 mM palmitic acid increased the abundance of Acsl3 (P!0.05) and Cpt2 tended to increase (PZ0.07) in cumulus cells, suggesting FAO was increased during maturation in response to stimulators and fatty acids. In conclusion, fatty acid and glucose metabolism are related to the mouse COC, as inhibition of FAO increases glucose consumption. Stimulation of FAO decreases glucose consumption and lipid stores, positively affecting subsequent embryo development, while an overabundance of fatty acid or reduced FAO negatively affects oocyte quality.

show abstract

Section: Discussionmentioning

confidence: 96%

Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

Paczkowski¹,

Schoolcraft²,

Krisher³

2014

Reproduction

View full text Add to dashboard Cite

show abstract

“…In hepatocytes of both normal and diabetic rats, glucose cycling between glucose and G6P was elevated when glycolysis was suppressed by an increase in fatty acids in the media (32)(33)(34) and the elevation of glucose cycling was associated with an increased flux through glucose 6-phosphatase (33). Lipid infusion rapidly increased hepatic glucose 6-phosphatase gene expression and protein content in rats (35).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, our current and previous (38,39) data confirm that suppression of plasma NEFA concentrations shifts the liver into a more glycolytic mode. In vitro evidence has shown that glycolysis is inhibited in isolated hepatocytes incubated with fatty acids (32,40). The shift toward glycolysis when fatty acid levels are low could result from a fall in citrate, one of the major inhibitors of phosphofructokinase, the first rate-determining enzyme in the glycolytic pathway (32,40).…”

Section: Discussionmentioning

confidence: 99%

Nonesterified Fatty Acids and Hepatic Glucose Metabolism in the Conscious Dog

et al. 2004

View full text Add to dashboard Cite

We used tracer and arteriovenous difference techniques in conscious dogs to determine the effect of nonesterified fatty acids (NEFAs) on net hepatic glucose uptake (NHGU E levated levels of nonesterified fatty acids (NEFAs) impair insulin-mediated suppression of endogenous glucose production under postabsorptive conditions (1-9). However, the relationship between NEFA concentrations and net splanchnic or hepatic glucose uptake (HGU) in the postprandial state is less clearly understood. NEFA concentrations and net hepatic or splanchnic uptake of NEFA fall during the postprandial period (10 -12). Postprandial NEFA concentrations are higher in individuals with type 2 diabetes than nondiabetic individuals, even though their insulin concentrations are also higher (13,14). Normally, the liver extracts approximately one-third of a glucose load delivered enterally or into the portal vein (15-17), but net HGU (NHGU) is reduced in individuals with type 2 diabetes (13,18) and in those at risk of developing type 2 diabetes (19,20). Whether an elevation of NEFA concentrations might contribute to impaired postprandial HGU has not been established.We hypothesized that the failure to suppress NEFA concentrations postprandially would reduce NHGU. To test this hypothesis, we studied conscious dogs under euinsulinemic-hyperglycemic conditions as a first step toward understanding the impact of elevated NEFA concentrations in conjunction with the relative insulin deficiency of type 2 diabetes. RESEARCH DESIGN AND METHODSStudies were carried out on conscious mongrel dogs of both sexes, fasted 42 h, and with a mean weight of 23.6 Ϯ 0.9 kg. The 42-h fast was chosen because it is a time when hepatic glycogen has reached a stable minimum in both dogs and humans (21,22). Approximately 16 days before study, each dog underwent a laparotomy for placement of ultrasonic flow probes (Transonic Systems, Ithaca, NY) around the portal vein and the hepatic artery, as well as insertion of sampling catheters into the left common hepatic vein, the portal vein, and a femoral artery, and the insertion of infusion catheters into a splenic and a jejunal vein (9). Diet, housing, protocol approval, criteria for study, and preparation for study were as previously described (15).Each experiment consisted of a 90-min equilibration period (Ϫ120 to Ϫ30 min), a 30-min basal period (Ϫ30 to 0 min), and a 240-min experimental period (0 -240 min). At Ϫ120 min, priming doses of [U-14 C]glucose (11 Ci/kg) and [3-3 H]glucose (34 Ci/kg) were given, and constant infusions of [U-14 C]glucose (0.4 Ci/min), [3-3 H]glucose (0.35 Ci/min), and indocyanine green dye (0.14 mg/min) (Sigma, St. Louis, MO) were initiated. A constant peripheral infusion of p-aminohippuric acid (PAH) (1.7 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) (Sigma) was also started at Ϫ120 min, continuing until 0 min. At 0 min, a constant peripheral infusion of somatostatin (0.8 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) (Bachem, Torrance, CA) was begun to suppress endogenous insulin and glucagon secretion, and porcine insulin (0.4 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ...

show abstract

“…The other major radioactive products of glucose and lactate metabolism (glucose, lactate, pyruvate, amino acids and water) were resolved by ion-exchange chromatography [7,211. Isotopic glycogen formation was measured as previously described [22].…”

Section: Methodsmentioning

confidence: 99%

The Contribution of Glucose Cycling to the Maintenance of Steady‐State Levels of Lactate by Hepatocytes During Glycolysis and Gluconeogenesis

Phillips

Clark

Henly

et al. 1995

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

When hepatocytes from fasted rats were incubated with 10 mM glucose, there was a linear accumulation of lactate and pyruvate for about 80 min after which steady-state concentrations of these metabolites became established. The rate of glycolysis, determined with [6-3H]glucose, was constant over the entire incubation period and was 50% greater than that calculated from carbon balance studies. This suggests that one-third of the glycolytic products formed were recycled to glucose. To enable study of the factors associated with the generation and maintenance of the lactate steady state and to measure accurately the carbon balance, incubations were performed using supraphysiological concentrations of glucose (20-80 mh"). Under these conditions the initial rate of lactate accumulation and its concentration at steady state were shown to be dependent on the concentration of extracellular glucose.Rates of glycolysis were also measured using 40 mM [6-3Hlglucose and [U-'"C]glucose added alone, or in combination with a steady-state lactate concentration (3 mM). There was no effect on the rate of glycolysis determined with [6-3H]glucose, even when lactate was present in the medium. The difference in rates between measurements with the two isotopes reflects the apparent degree of glucose recycling which in the absence and presence of added lactate increased from 0.26 to 0.54 pmol C, equivalents . min-' . g-' respectively. Identical studies employing [U-'"C]lactate showed that glucose and CO, were the major products of lactate metabolism under steady-state conditions and that the formation of lactate from [1J-'4C]glucose exactly balanced the rate of lactate removal as a result of oxidation and gluconeogenesis. These studies provide evidence for the concomitant operation of glycolysis and gluconeogenesis, even in the presence of high glucose concentrations. They also demonstrate that lactate steady states are achieved not by the cessation of glycolysis but rather by the removal of lactate and pyruvate at a rate equal tlo that of their production.Keywords. Glucose cycling ; glycolysis ; gluconeogenesis ; hepatocyte ; lactate ; steady state.The liver is the principle organ responsible for controlling lactate levels in the blood [I -31. Any rise in blood lactate concentration, due for example to muscular activity, is rapidly corrected by the removal of lactate by the liver and its conversion to glucose that can then pass back to the muscle, providing the fuel for further glycolysis, a process known as the Cori cycle [4]. However, this cycling of glucose and lactate need not involve muscle but can take place entirely within the liver, with hepatic glycolysis anid gluconeogenesis occurring concomitantly [5-81. The phenomenon of glucose cycling has aroused considerable interest, bet the factors that determine the rate of carbon flow under various physiological conditions remain uncertain.A feature of the iinterrelationship between glucose and lactate metabolism reported in preliminary studies [9, 101 is that, when glycolysis is init...

show abstract

Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes

Cited by 26 publications

References 39 publications

Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

Nonesterified Fatty Acids and Hepatic Glucose Metabolism in the Conscious Dog

The Contribution of Glucose Cycling to the Maintenance of Steady‐State Levels of Lactate by Hepatocytes During Glycolysis and Gluconeogenesis

Contact Info

Product

Resources

About