Palmitoleic acid (16:1n7) increases oxygen consumption, fatty acid oxidation and ATP content in white adipocytes

Isolated bovine cerebral microvessels (ICMV) were incubated with different metabolic fuels to determine the effect of each of them on microvessel energy state. With no fuel added to the medium, the ATP/ADP generally decreased from initial values of 1.5-3 down to 1-1.5 over 4 h; the ATP content also declined approximately 50%. In contrast, with glucose present, the ATP/ADP increased, and the ATP content was maintained. Pyruvate, beta-hydroxybutyrate, glutamate, and oleate were ineffective; oleate added together with carnitine gave some improvement but less than with glucose. Oxygen consumption by ICMV did not differ appreciably in fuel-free or glucose-containing medium. Addition of an inhibitor of fatty acid oxidation, 2-tetradecylglycidate, depressed the ATP/ADP. These results suggest that ICMV require glycolysis to maintain both their content of ATP and their ATP/ADP. They also suggest that endogenous lipid is an important fuel for isolated microvessels.

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Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00437.2015 ◽

2016 ◽

Vol 310 (6) ◽

pp. E452-E460 ◽

Cited By ~ 25

Author(s):

K. J. Mather ◽

G. D. Hutchins ◽

K. Perry ◽

W. Territo ◽

R. Chisholm ◽

...

Keyword(s):

Type 2 Diabetes ◽

Oxygen Consumption ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Metabolic Flexibility ◽

Work Efficiency ◽

Myocardial Fatty Acid ◽

Fuel Selection

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[18F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([11C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m−2·min−1) to 3-h saline infusion. Lean controls ( n = 10) were compared with glycemically controlled volunteers with T2DM ( n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption ( P = 0.04) and perfusion ( P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids ( P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions ( P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups ( P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM ( P = 0.003). Myocardial work efficiency was lower in T2DM ( P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization ( P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM.

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Palmitoleic Acid Decreases Non-alcoholic Hepatic Steatosis and Increases Lipogenesis and Fatty Acid Oxidation in Adipose Tissue From Obese Mice

Frontiers in Endocrinology ◽

10.3389/fendo.2020.537061 ◽

2020 ◽

Vol 11 ◽

Author(s):

Maysa M. Cruz ◽

Jussara J. Simão ◽

Roberta D. C. C. de Sá ◽

Talita S. M. Farias ◽

Viviane S. da Silva ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Hepatic Steatosis ◽

Fatty Acid Oxidation ◽

Palmitoleic Acid ◽

Acid Oxidation ◽

Obese Mice

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Evidence that the flux control coefficient of the respiratory chain is high during gluconeogenesis from lactate in hepatocytes from starved rats. Implications for the hormonal control of gluconeogenesis and action of hypoglycaemic agents

Biochemical Journal ◽

10.1042/bj2470449 ◽

1987 ◽

Vol 247 (2) ◽

pp. 449-457 ◽

Cited By ~ 34

Author(s):

H J Pryor ◽

J E Smyth ◽

P T Quinlan ◽

A P Halestrap

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Respiratory Chain ◽

Glucose Production ◽

Hormonal Control ◽

Acid Oxidation ◽

Control Coefficient ◽

Atp Content ◽

Flux Control ◽

Flux Control Coefficient

1. Increasing concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), a mild respiratory-chain inhibitor [Halestrap (1987) Biochim. Biophys. Acta 927, 280-290], caused progressive inhibition of glucose production from lactate + pyruvate by hepatocytes from starved rats incubated in the presence or absence of oleate and gluconeogenic hormones. 2. No significant changes in tissue ATP content were observed, but there were concomitant decreases in ketone-body output and cytochrome c reduction and increases in NADH fluorescence and the ratios of [lactate]/[pyruvate] and [beta-hydroxybutyrate]/[acetoacetate]. 3. The inhibition by DCMU of palmitoylcarnitine oxidation by isolated liver mitochondria was used to calculate a flux control coefficient of the respiratory chain towards gluconeogenesis. In the presence of 1 mM-oleate, the calculated values were 0.61, 0.39 and 0.25 in the absence of hormone and in the presence of glucagon or phenylephrine respectively, consistent with activation of the respiratory chain in situ as previously suggested [Quinlan & Halestrap (1986) Biochem. J. 236, 789-800]. 4. Cytoplasmic oxaloacetate concentrations were shown to decrease under these conditions, implying inhibition of pyruvate carboxylase. 5. Inhibition of gluconeogenesis from fructose and dihydroxyacetone was also observed with DCMU and was accompanied by an increased output of lactate + pyruvate, suggesting that activation of pyruvate kinase was occurring. With the latter substrate, measurements of tissue ADP and ATP contents showed that DCMU caused a small fall in [ATP]/[ADP] ratio. 6. Two inhibitors of fatty acid oxidation, pent-4-enoate and 2-tetradecylglycidate, were shown to abolish and to decrease respectively the effects of hormones, but not valinomycin, on gluconeogenesis from lactate + pyruvate, without changing tissue ATP content. 7. It is concluded that the hormonal increase in mitochondrial matrix volume stimulates fatty acid oxidation and respiratory-chain activity, allowing stimulation of pyruvate carboxylation and thus gluconeogenesis to occur without major changes in [ATP]/[ADP] or [NADH]/[NAD+] ratios. 8. The high flux control coefficient of the respiratory chain towards gluconeogenesis may account for the hypoglycaemic effect of mild respiratory-chain inhibitors.

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Abstract 328: Med13 regulates cardiac metabolism

Circulation Research ◽

10.1161/res.113.suppl_1.a328 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Kedryn K Baskin ◽

Chad E Grueter ◽

Christine M Kusminski ◽

Philipp E Scherer ◽

Rhonda Bassel-Duby ◽

...

Keyword(s):

Oxygen Consumption ◽

Fatty Acid ◽

Glucose Uptake ◽

Fatty Acid Oxidation ◽

Electron Flow ◽

Krebs Cycle ◽

Cardiac Metabolism ◽

Acid Oxidation ◽

Intermediary Metabolites ◽

Consumption Rates

Background: The heart is a metabolic organ that primarily utilizes fatty acids as energy substrate. While it is well established that the heart is metabolically flexible, the transcriptional network regulating cardiac metabolism is only partially understood. We have previously demonstrated that cardiac overexpression of Med13, a component of the Mediator Complex that regulates transcription, results in a lean phenotype with enhanced basal metabolic rates. We now investigate the mechanisms contributing to metabolic changes in mice with cardiac over-expression of Med13(Med13cTg). Methods and Results: Cardiac fludeoxyglucose (18F-FDG)-PET imaging analysis revealed that Med13cTg hearts take up more glucose than wild type littermates. To determine pathways responsible for enhanced glucose uptake, ventricles from Med13cTg mice were subjected to RNA-seq and metabolomic analysis. The expression of fatty acid oxidation genes was decreased in Med13cTg hearts, accompanied by an increase in acyl CoA and a decrease in acetyl CoA. These data suggest that beta oxidation is decreased in Med13cTg hearts. Mitochondria function was therefore determined in Med13cTg hearts by performing electron-flow analyses and assessing oxygen consumption rates. Indeed, oxygen consumption rates were decreased in mitochondria isolated from Med13cTg hearts. Expression of Krebs Cycle genes and corresponding intermediary metabolites were also decreased in Med13cTg hearts, suggesting decreased flux through this pathway as well. Conclusions: Overexpression of Med13 in the heart increases glucose uptake and decreases fatty acid oxidation in the heart. We speculate that Med13 transcriptionally regulates key mediators of cardiac metabolism. The mechanisms by which this occurs are currently under investigation.

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