scholarly journals Nonoxidative Free Fatty Acid Disposal Is Greater in Young Women than Men

2011 ◽  
Vol 96 (2) ◽  
pp. 541-547 ◽  
Author(s):  
Christina Koutsari ◽  
Rita Basu ◽  
Robert A. Rizza ◽  
K. Sreekumaran Nair ◽  
Sundeep Khosla ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Specific Interaction ◽  
Serum Triglyceride ◽  
Nitrogen Excretion ◽  
Whole Body ◽  
Acid Oxidation ◽  
Peripheral Insulin Sensitivity

abstract Context: Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal. Objective: The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia. Design: We measured: systemic FFA turnover using a continuous iv infusion of [9–10, 3H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model. Setting: the study was conducted at the Mayo Clinic General Clinical Research Center. Participants: Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men). Interventions: There were no interventions. Main Outcome Measures: Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation. Results: Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women. Conclusions: Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities.

Insulin Resistance of Stress: Sites and Mechanisms

1993 ◽  
Vol 85 (5) ◽  
pp. 525-535 ◽  
Author(s):  
Luigi S. Brandi ◽  
Donatella Santoro ◽  
Andrea Natali ◽  
Fiorella Altomonte ◽  
Simona Baldi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Plasma Free Fatty Acid ◽  
Whole Body ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Free Fatty Acid Oxidation

1. Stress is associated with a severe, yet reversible, form of insulin resistance. The aim of this study was to quantify the kinetics of insulin action (sensitivity and responsiveness) on intermediary metabolism during post-surgical stress. 2. We studied nine patients 6–8 h after major uncomplicated surgery, and eight healthy subjects matched for age, weight, glucose tolerance and duration of fast. A three-step isoglycaemic insulin clamp was combined with indirect calorimetry, [6-3H]glucose infusion and the forearm technique. 3. The following significant (P <0.05 or less) abnormalities were found in the patients. Hepatic glucose production was higher at baseline, and less suppressed by insulin. Whole-body glucose disposal was impaired at all insulin doses (by 33–60%). Glucose oxidation was depressed throughout the dose range but its increments in response to insulin were normal. In contrast, non-oxidative glucose disposal was essentially unresponsive. At all insulin levels, forearm glucose extraction was markedly depressed and forearm lactate release was in excess of concurrent glucose uptake, suggesting ongoing glycogenolysis despite insulin. Total lipolysis (plasma free fatty acid and glycerol levels) promptly responded to insulin but remained higher than in the control subjects throughout. In the forearm, even the highest insulin dose could not suppress net free fatty acid and glycerol release. Total lipid oxidation was increased throughout the insulin range, and calculated direct free fatty acid (as opposed to plasma free fatty acid) oxidation was virtually unaffected by insulin. Protein oxidation was slightly (35%) increased, but was suppressed normally in response to insulin. Energy expenditure was 20% higher at baseline, and tailed to rise with insulin. Arterial blood pH values were consistently (if slightly) lower, and net forearm proton release was higher, both at baseline and daring insulin infusion. 4. Post-surgical unsulin resistance is characterized by normal sensitivity but decreased responsiveness of glucose oxidation, lipolysis and plasma free fatty acid oxidation, whereas glycogen synthesis and direct free fatty acid oxidation are virtually unresponsive. For both glucose and lipid metabolism, the insulin resistance is particularly severe in forearm tissues, in which mild metabolic acidosis may play an additional role.

Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle

2006 ◽  
Vol 290 (6) ◽  
pp. E1296-E1303 ◽  
Author(s):  
Jeanette E. Kuhl ◽  
Neil B. Ruderman ◽  
Nicolas Musi ◽  
Laurie J. Goodyear ◽  
Mary Elizabeth Patti ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Physical Training ◽  
Human Muscle ◽  
Whole Body ◽  
Acid Oxidation ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Malonyl Coa ◽  
Expression And Activity

The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased V̇o2 max by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25–30%) in the concentration of malonyl-CoA were observed after training, 24–36 h after the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α (PGC-1α), a regulator of transcription that has been linked to the mediation of MCD expression by PPARα, was also increased (3-fold). In studies also conducted 24–36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonyl-CoA is diminished in muscle after physical training, most likely because of PGC-1α-mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole body insulin sensitivity and fatty acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated.

scholarly journals Sustained endogenous glucose production, diminished lipolysis and non-esterified fatty acid appearance and oxidation in non-obese women at high risk of type 2 diabetes

2006 ◽  
Vol 155 (3) ◽  
pp. 469-476 ◽  
Author(s):  
Shareen Forbes ◽  
Stephen Robinson ◽  
Jason Dungu ◽  
Victor Anyaoku ◽  
Peter Bannister ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
At Risk ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Glucose Production ◽  
Whole Body ◽  
Acid Oxidation ◽  
Obese Women

Objective: To evaluate early defects in glucose production, lipolysis and fatty acid oxidation in non-obese, normally glucose tolerant women, who are nevertheless at risk of type 2 diabetes. Methods: Ten women with previous gestational diabetes (pGDM) and ten controls were studied in two 4 h infusions of stable isotopes 6,6-2H2-glucose, 1-13C-palmitate, and 1,1,2,3,3-2H5-glycerol with and without infusion of adrenaline. Fatty acid oxidation was quantified using indirect calorimetry and 13CO2 measurements. Insulin sensitivity was evaluated using the short insulin tolerance test. Results: The pGDM and control women were non-obese and carefully matched for body mass index and fat mass. Whole body insulin sensitivity and basal insulin concentrations did not differ significantly but basal glucose concentrations were increased in women with pGDM. During a 0.9% saline infusion, glucose appearance was not significantly different at the first (90–120 min) and second (210–240 min) steady states. However, glucose appearance decreased in controls but was maintained in the pGDM women (−0.33 ± 0.02 vs −0.03 ± 0.08 mg/kg per min; P = 0.004). Basal glycerol appearance (0.27 ± 0.02 vs 0.38 ± 0.03 mg/kg per min; P = 0.02), palmitate appearance (0.74 ± 0.09 vs 1.05 ± 0.09 mg/kg per min; P = 0.03) and palmitate oxidation (0.07 ± 0.01 vs 0.10 ± 0.01 mg/kg per min; P = 0.03) were lower in the pGDM women. During the adrenaline infusion, changes in glucose, glycerol and palmitate concentrations and kinetics were similar in both groups. Conclusions: Sustained glucose production during fasting is an early abnormality in non-obese subjects at risk of type 2 diabetes. Lipolysis and non-esterified fatty acid appearance and oxidation are diminished, suggesting an increased tendency to store fat. The observations are not readily attributable to differences in insulin or catecholamine sensitivity.

Effect of Menstrual Phase on the Acetate Correction Factor Used in Metabolic Tracer Studies

2003 ◽  
Vol 28 (6) ◽  
pp. 818-830 ◽  
Author(s):  
Tanja Oosthuyse ◽  
Andrew N. Bosch ◽  
Susan Jackson
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Correction Factor ◽  
Tricarboxylic Acid Cycle ◽  
Whole Body ◽  
Acid Oxidation ◽  
Exchange Reactions ◽  
Substrate Utilisation ◽  
Free Fatty Acid Oxidation

The acetate correction factor is used to account for retention of carbon label in exchange reactions of the tricarboxylic acid cycle in studies estimating free fatty acid oxidation with carbon-labeled tracers. Previous evidence indicates that substrate utilisation and metabolic rate vary across the menstrual cycle, which may alter the correction factor. We therefore derived the acetate correction factor for each of three menstrual phases (early follicular [EF], late follicular [LF], and midluteal [ML] phase) from the fractional recovery of 13CO2 from a constant infusion of sodium-[1-13C]acetate during 90 min of submaximal exercise (60%[Formula: see text]) in sedentary eumenorrhoeic women. There was no difference in the correction factor between the EF and LF or the LF and ML phases, but the correction factor derived in the ML phase was significantly lower than in the EF phase (p < 0.05). Neither energy expenditure nor whole body substrate utilisation during exercise varied significantly between menstrual phases and therefore cannot explain the observed difference in the correction factor. The lower correction factor in the ML phase, compared to the EF phase, would result in only a small increase of ∼6% in the calculated plasma free fatty acid oxidation rate. Key words: carbon isotopes, women, ovarian hormones, exercise, substrate oxidation

Meal composition affects postprandial fatty acid oxidation

1993 ◽  
Vol 264 (6) ◽  
pp. R1065-R1070 ◽  
Author(s):  
D. M. Surina ◽  
W. Langhans ◽  
R. Pauli ◽  
C. Wenk
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Nutrient Utilization ◽  
Whole Body ◽  
Acid Oxidation ◽  
Plasma Ffa ◽  
Hepatic Fatty Acid Oxidation ◽  
Beta Hydroxybutyrate ◽  
Chain Fatty Acids

The influence of macronutrient content of a meal on postprandial fatty acid oxidation was investigated in 13 Caucasian males after consumption of a high-fat (HF) breakfast (33% carbohydrate, 52% fat, 15% protein) and after an equicaloric high-carbohydrate (HC) breakfast (78% carbohydrate, 6% fat, 15% protein). The HF breakfast contained short- and medium-chain fatty acids, as well as long-chain fatty acids. Respiratory quotient (RQ) and plasma beta-hydroxybutyrate (BHB) were measured during the 3 h after the meal as indicators of whole body substrate oxidation and hepatic fatty acid oxidation, respectively. Plasma levels of free fatty acids (FFA), triglycerides, glucose, insulin, and lactate were also determined because of their relationship to nutrient utilization. RQ was significantly lower and plasma BHB was higher after the HF breakfast than after the HC breakfast, implying that more fat is burned in general and specifically in the liver after an HF meal. As expected, plasma FFA and triglycerides were higher after the HF meal, and insulin and lactate were higher after the HC meal. In sum, oxidation of ingested fat occurred in response to a single HF meal.

Effect of adipocyte β3-adrenergic receptor activation on the type 2 diabetic MKR mice

2006 ◽  
Vol 290 (6) ◽  
pp. E1227-E1236 ◽  
Author(s):  
Hyunsook Kim ◽  
Patricia A. Pennisi ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
William Jou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Receptor Activation ◽  
Whole Body ◽  
Acid Oxidation ◽  
Adrenergic Agonists ◽  
Nonobese Diabetic ◽  
Type 2 Diabetic

The antiobesity and antidiabetic effects of the β3-adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β3-adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β3-adrenergic agonists in nonobese diabetic subjects.

Malonyl-CoA content and fatty acid oxidation in rat muscle and liver in vivo

2000 ◽  
Vol 279 (2) ◽  
pp. E259-E265 ◽  
Author(s):  
David Chien ◽  
David Dean ◽  
Asish K. Saha ◽  
J. P. Flatt ◽  
Neil B. Ruderman
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acyl ◽  
Whole Body ◽  
Acid Oxidation ◽  
Malonyl Coa ◽  
Plasma Ffa ◽  
Gastrocnemius Muscles ◽  
Time Point

Malonyl-CoA acutely regulates fatty acid oxidation in liver in vivo by inhibiting carnitine palmitoyltransferase. Thus rapid increases in the concentration of malonyl-CoA, accompanied by decreases in long-chain fatty acyl carnitine (LCFA-carnitine) and fatty acid oxidation have been observed in liver of fasted-refed rats. It is less clear that it plays a similar role in skeletal muscle. To examine this question, whole body respiratory quotients (RQ) and the concentrations of malonyl-CoA and LCFA-carnitine in muscle were determined in 48-h-starved rats before and at various times after refeeding. RQ values were 0.82 at baseline and increased to 0.93, 1.0, 1.05, and 1.09 after 1, 3, 12, and 18 h of refeeding, respectively, suggesting inhibition of fat oxidation in all tissues. The increases in RQ at each time point correlated closely ( r = 0.98) with increases (50–250%) in the concentration of malonyl-CoA in soleus and gastrocnemius muscles and decreases in plasma FFA and muscle LCFA-carnitine levels. Similar changes in malonyl-CoA and LCFA-carnitine were observed in liver. The increases in malonyl-CoA in muscle during refeeding were not associated with increases in the assayable activity of acetyl-CoA carboxylase (ACC) or decreases in the activity of malonyl-CoA decarboxylase (MCD). The results suggest that, during refeeding after a fast, decreases in fatty acid oxidation occur rapidly in muscle and are attributable both to decreases in plasma FFA and increases in the concentration of malonyl-CoA. They also suggest that the increase in malonyl-CoA in this situation is not due to changes in the assayable activity of either ACC or MCD or an increase in the cytosolic concentration of citrate.

scholarly journals Weight Reduction and the Impaired Plasma-Derived Free Fatty Acid Oxidation in Type 2 Diabetic Subjects1

2001 ◽  
Vol 86 (4) ◽  
pp. 1638-1644
Author(s):  
E. E. Blaak ◽  
B. H. R. Wolffenbuttel ◽  
W. H. M. Saris ◽  
M. M. A. L. Pelsers ◽  
A. J. M. Wagenmakers
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Weight Reduction ◽  
Acid Oxidation ◽  
Free Fatty Acid Oxidation ◽  
Type 2 Diabetic

Effects of blockade of fatty acid oxidation on whole body and tissue-specific glucose metabolism in rats

1993 ◽  
Vol 265 (4) ◽  
pp. E592-E600 ◽  
Author(s):  
A. B. Jenkins ◽  
L. H. Storlien ◽  
G. J. Cooney ◽  
G. S. Denyer ◽  
I. D. Caterson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Pyruvate Dehydrogenase ◽  
Glucose Utilization ◽  
Whole Body ◽  
Acid Oxidation ◽  
Tissue Specific ◽  
Glucose Output

We examined the effect of the long-chain fatty acid oxidation blocker methyl palmoxirate (methyl 2-tetradecyloxiranecarboxylate, McN-3716) on glucose metabolism in conscious rats. Fasted animals [5 h with or without hyperinsulinemia (100 mU/l) and 24 h] received methyl palmoxirate (30 or 100 mg/kg body wt po) or vehicle 30 min before a euglycemic glucose clamp. Whole body and tissue-specific glucose metabolism were calculated from 2-deoxy-[3H]-glucose kinetics and accumulation. Oxidative metabolism was assessed by respiratory gas exchange in 24-h fasted animals. Pyruvate dehydrogenase complex activation was determined in selected tissues. Methyl palmoxirate suppressed whole body lipid oxidation by 40-50% in 24-h fasted animals, whereas carbohydrate oxidation was stimulated 8- to 10-fold. Whole body glucose utilization was not significantly affected by methyl palmoxirate under any conditions; hepatic glucose output was suppressed only in the predominantly gluconeogenic 24-h fasted animals. Methyl palmoxirate stimulated glucose uptake in heart in 24-h fasted animals [15 +/- 5 vs. 220 +/- 28 (SE) mumol x 100 g-1 x min-1], with smaller effects in 5-h fasted animals with or without hyperinsulinemia. Methyl palmoxirate induced significant activation of pyruvate dehydrogenase in heart in the basal state, but not during hyperinsulinemia. In skeletal muscles, methyl palmoxirate suppressed glucose utilization in the basal state but had no effect during hyperinsulinemia; pyruvate dehydrogenase activation in skeletal muscle was not affected by methyl palmoxirate under any conditions. The responses in skeletal muscle are consistent with the operation of a mechanism similar to the Pasteur effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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