Stimulation of fatty acid oxidation by a 3-thia fatty acid reduces triacylglycerol secretion in cultured rat hepatocytes.

In vivo administration of GH induces lipolysis and lipid oxidation. However, it is not clear whether the stimulation of lipid oxidation is a direct effect of GH or is driven by increased substrate supply secondary to lipolysis. An in vitro bioassay has been established for assessing β-oxidation of fatty acids in mitochondria, based on the measurement of conversion of tritiated palmitic acid to 3H2O by fibroblasts in culture. We have modified this assay to investigate whether GH stimulates fatty acid oxidation. GH stimulated oxidation of palmitic acid maximally by 26.7 ± 2.5% (mean ± sem; P < 0.0001). The stimulation was biphasic, with the oxidation rate increasing with increasing GH concentration to a peak response at 1.5 nmol/L and declining to a level not significantly different from control thereafter. Insulin-like growth factor-I at concentrations of up to 250 nmol/L had no significant effect on fatty acid oxidation. GH-binding protein attenuated the effect of GH. An anti-GH receptor (GHR) antibody (MAb263), which dimerizes the receptor and induces GH-like biological actions, significantly stimulated fatty acid oxidation. Another anti-GHR antibody (MAb5), which prevents receptor dimerization, suppressed GH action. In summary, GH directly stimulated fatty acid oxidation, an action not mediated by insulin-like growth factor-I. Dimerization of GHRs was necessary for this effect. This bioassay is a practical tool for studying the regulatory effects of GH on lipid oxidation.

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Effect of starvation and diabetes on the sensitivity of carnitine palmitoyltransferase I to inhibition by 4-hydroxyphenylglyoxylate

Biochemical Journal ◽

10.1042/bj2430405 ◽

1987 ◽

Vol 243 (2) ◽

pp. 405-412 ◽

Cited By ~ 11

Author(s):

T W Stephens ◽

R A Harris

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Rat Hepatocytes ◽

Isolated Hepatocytes ◽

Carnitine Palmitoyltransferase ◽

Time Dependent ◽

Acid Oxidation ◽

Moderate Increase ◽

Dependent Manner ◽

Carnitine Palmitoyltransferase I

The sensitivity of carnitine palmitoyltransferase I to inhibition by 4-hydroxyphenylglyoxylate was decreased markedly in liver mitochondria isolated from either 48 h-starved or streptozotocin-diabetic rats. These treatments of the rat also decreased the sensitivity of fatty acid oxidation by isolated hepatocytes to inhibition by this compound. Furthermore, incubation of hepatocytes prepared from fed rats with N6O2′-dibutyryl cyclic AMP also decreased the sensitivity, whereas incubation of hepatocytes prepared from starved rats with lactate plus pyruvate had the opposite effect on 4-hydroxyphenylglyoxylate inhibition of fatty acid oxidation. The sensitivity of carnitine palmitoyltransferase I of mitochondria to 4-hydroxyphenylglyoxylate increased in a time-dependent manner, as previously reported for malonyl-CoA. Likewise, oleoyl-CoA activated carnitine palmitoyltransferase I in a time-dependent manner and prevented the sensitization by 4-hydroxyphenylglyoxylate. Increased exogenous carnitine caused a moderate increase in fatty acid oxidation by hepatocytes under some conditions and a decreased 4-hydroxyphenylglyoxylate inhibition of fatty acid oxidation at low oleate concentration, without decreasing the difference in 4-hydroxyphenylglyoxylate inhibition between fed- and starved-rat hepatocytes. Time-dependent changes in the conformation of carnitine palmitoyltransferase I or the membrane environment may be involved in differences among nutritional states in 4-hydroxyphenylglyoxylate-sensitivity of carnitine palmitoyltransferase I.

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Stimulation of polyunsaturated fatty acid oxidation in myocytes by regulating its cellular uptake

Life Sciences ◽

10.1016/0024-3205(91)90002-s ◽

1991 ◽

Vol 49 (3) ◽

pp. 185-192 ◽

Cited By ~ 2

Author(s):

Salah Abdel-aleem ◽

Mostafa Badr ◽

Crist Frangakis

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Polyunsaturated Fatty Acid ◽

Cellular Uptake ◽

Acid Oxidation ◽

Stimulation Of

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Fatty Acid Oxidation by Skeletal Muscle During Rest and Activity

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.194.2.379 ◽

1958 ◽

Vol 194 (2) ◽

pp. 379-386 ◽

Cited By ~ 154

Author(s):

Irving B. Fritz ◽

Don G. Davis ◽

Robert H. Holtrop ◽

Harold Dundee

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Palmitic Acid ◽

Fatty Acid Oxidation ◽

Latissimus Dorsi ◽

Acid Metabolism ◽

Fat Metabolism ◽

Acid Oxidation ◽

Stimulation Of

The metabolism of C14-labeled acetate, octanoate and palmitate by isolated skeletal muscle (latissimus dorsi and diaphragm) from normal, fed rats has been examined. The rates at which these substrates were converted to C14O2 have been shown to vary with concentration, temperature, functional state of the muscle, and the presence of albumin. Increased concentration of fatty acids led to enhanced conversion of substrate to C14O2. Electrical stimulation of muscles under tension resulted in approximately a 60% increase in oxygen consumption and about a 100% rise in fatty acid oxidation. The addition of glucose did not alter the rate of fatty acid metabolism by muscle. The addition of bovine albumin at concentrations up to approximately 1 µm albumin/7 µm palmitate resulted in augmented palmitic acid oxidation. However, at concentrations of albumin greater than 1 µm albumin/7 µm palmitate, palmitic acid degradation by resting diaphragm was inhibited, suggesting a firmer binding of fatty acid to albumin. The Q10 for palmitic acid oxidation by resting diaphragm was 2.23 in the absence of added albumin between 25° and 37°C. The data are discussed in relation to the present concepts of fat metabolism and transport in vivo. It is suggested that fat degradation in isolated muscle may provide an energy source during activity.

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