Physiological Levels of Plasma Non-Esterified Fatty Acids Impair Forearm Glucose Uptake in Normal Man

1990 ◽  
Vol 79 (2) ◽  
pp. 167-174 ◽  
Author(s):  
M. Walker ◽  
G. R. Fulcher ◽  
C. Catalano ◽  
G. Petranyi ◽  
H. Orskov ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Uptake ◽  
Whole Body ◽  
Saline Control ◽  
Acid Uptake ◽  
Lipid Infusion ◽  
Metabolite Exchange ◽  
Glucose Fatty Acid Cycle ◽  
And Control

1. The purpose of the present study was to maintain physiological plasma non-esterified fatty acid levels and to (i) examine their effect on skeletal muscle insulin-stimulated glucose uptake and metabolite exchange using the forearm technique, and (ii) evaluate their effect on whole-body glucose uptake and fuel oxidation. 2. Intralipid (10%) and heparin (Lipid) or saline (Control) was administered to eight healthy male subjects on separate occasions for 210 min. Insulin, glucagon and somatostatin were administered from 60 to 210 min in each study and euglycaemia was maintained. 3. Plasma non-esterified fatty acid levels plateaued at 420 ±50 μmol/l with the Lipid infusion but were completely suppressed during the Control clamp. Forearm non-esterified fatty acid uptake increased with the Lipid infusion (+ 50±10 nmol min−1 100 ml−1 of forearm) and was accompanied by a significant decrease in forearm glucose uptake (+ 3.23 ± 0.25 versus + 3.65 ± 0.35 μmol min−1 100 ml−1 of forearm, Lipid and Control, respectively; P < 0.05) and alanine release (–84±12 versus −113 ± 15 nmol min−1 100 ml−1 of forearm, Lipid and Control, respectively; P < 0.05). 4. Whole-body glucose uptake showed a comparable decrease with the Lipid infusion (6.36 ±0.81 versus 6.85±0.66 mg min−1 kg−1; P < 0.05) and was accompanied by an increase in lipid oxidation (0.33 ±0.08 versus 0.16 ±0.05 mg min−1 kg−1; P < 0.02) and a decrease in glucose oxidation (2.93 ±0.23 versus 3.30±0.20 mg min−1 kg−1; P < 0.05). 5. We conclude that the maintenance of physiological plasma non-esterified fatty acid levels is associated with a decrease in forearm and whole-body insulin-stimulated glucose uptake. The changes in substrate oxidation and forearm alanine exchange provide support for the operation of the glucose—fatty acid cycle.

scholarly journals Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake

2017 ◽  
Vol 122 (5) ◽  
pp. 1188-1197 ◽  
Author(s):  
Kumail K. Motiani ◽  
Anna M. Savolainen ◽  
Jari-Joonas Eskelinen ◽  
Jussi Toivanen ◽  
Tamiko Ishizu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Interval Training ◽  
Fatty Acid Uptake ◽  
Whole Body ◽  
Moderate Intensity ◽  
Acid Uptake ◽  
Continuous Training

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity ( P = 0.001) and whole body insulin sensitivity ( P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) ( P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = −4%; MICT = 13%) ( P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = −6%; MICT = −48%) ( P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = −38%) ( P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism. NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques available. We also show the importance of exercise intensity in inducing these changes.

scholarly journals Protein Kinase D1 Is Essential for Contraction-induced Glucose Uptake but Is Not Involved in Fatty Acid Uptake into Cardiomyocytes

2011 ◽  
Vol 287 (8) ◽  
pp. 5871-5881 ◽  
Author(s):  
Ellen Dirkx ◽  
Robert W. Schwenk ◽  
Will A. Coumans ◽  
Nicole Hoebers ◽  
Yeliz Angin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Protein Kinase D1

Effect of glycemia and nonesterified fatty acids on forearm glucose uptake in normal humans

1991 ◽  
Vol 261 (3) ◽  
pp. E304-E311 ◽  
Author(s):  
M. Walker ◽  
G. R. Fulcher ◽  
C. F. Sum ◽  
H. Orskov ◽  
K. G. Alberti
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Glucose Uptake ◽  
Whole Body ◽  
Glucose Disposal ◽  
Nonesterified Fatty Acid ◽  
Nonesterified Fatty Acids ◽  
Glucose Levels ◽  
And Control ◽  
Blood Glucose Concentrations

The purpose of this study was to examine the effect of physiological plasma nonesterified fatty acid (NEFA) levels on insulin-stimulated forearm and whole body glucose uptake and substrate oxidation during euglycemia and hyperglycemia. Seven healthy men received Intralipid and heparin for 210 min in two studies, with saline as control in two further studies. Insulin (0.05 U.kg-1.h-1) was infused from 60 min, and euglycemia was maintained during lipid (EL) and control (EC) studies, and hyperglycemia was maintained in the other studies (HL and HC). Forearm NEFA uptake was comparable in the lipid studies (+61 +/- 10 and +52 +/- 8 nmol.100 ml forearm-1.min-1, EL and HL) and was suppressed in the controls. With Intralipid, forearm glucose uptake decreased during euglycemia but not during hyperglycemia (+3.85 +/- 0.34 vs. +3.34 +/- 0.25 mumol.100 ml forearm-1.min-1, EC vs. EL, P less than 0.02), with comparable changes in whole body glucose uptake. Glucose oxidation and forearm alanine release decreased with Intralipid at both blood glucose levels, with no significant change in the rates of nonoxidative glucose disposal. These observations support the operation of the glucose-fatty acid cycle at physiological plasma NEFA levels at both blood glucose concentrations, but this was associated with a decrease in peripheral insulin sensitivity only during euglycemia.

Organ-specific dietary fatty acid uptake in humans using positron emission tomography coupled to computed tomography

2011 ◽  
Vol 300 (3) ◽  
pp. E445-E453 ◽  
Author(s):  
Sébastien M. Labbé ◽  
Thomas Grenier-Larouche ◽  
Etienne Croteau ◽  
François Normand-Lauzière ◽  
Frédérique Frisch ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Distribution ◽  
Standard Uptake Value ◽  
Fatty Acid Uptake ◽  
Dietary Fatty Acid ◽  
Whole Body ◽  
Acid Uptake ◽  
Noninvasive Method ◽  
Liquid Meal ◽  
Positron Emission

A noninvasive method to determine postprandial fatty acid tissue partition may elucidate the link between excess dietary fat and type 2 diabetes. We hypothesized that the positron-emitting fatty acid analog 14( R, S)-[18F]fluoro-6-thia-heptadecanoic acid (18FTHA) administered orally during a meal would be incorporated into chylomicron triglycerides, allowing determination of interorgan dietary fatty acid uptake. We administered 18FTHA orally at the beginning of a standard liquid meal ingested in nine healthy men. There was no significant 18FTHA uptake in the portal vein and the liver during the 1st hour. Whole body PET/CT acquisition revealed early appearance of 18FTHA in the distal thoracic duct, reaching a peak at time 240 min. 18FTHA mean standard uptake value increased progressively in the liver, heart, quadriceps, and subcutaneous and visceral adipose tissues between time 60 and 240 min. Most circulating 18F activity between time 0 and 360 min was recovered into chylomicron triglycerides. Using Triton WR-1339 treatment in rats that received 18FTHA by gavage, we confirmed that >90% of this tracer reached the circulation as triglycerides. This novel noninvasive method to determine tissue dietary fatty acid distribution in humans should prove useful in the study of the mechanisms leading to lipotoxicity.

Myocardial substrate uptake in lambs with and without aortopulmonary shunts during strenuous exercise

1993 ◽  
Vol 75 (2) ◽  
pp. 505-512
Author(s):  
J. W. Gratama ◽  
M. Dalinghaus ◽  
J. J. Meuzelaar ◽  
A. M. Gerding ◽  
J. H. Koers ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Substrate Uptake ◽  
O2 Consumption ◽  
Myocardial Substrate ◽  
Myocardial O2 Consumption ◽  
And Control

Increased myocardial fatty acid uptake during acute exercise could adversely affect myocardial O2 consumption in lambs with left-to-right shunts, which would be unfavorable in view of their decreased coronary blood flow reserve. Therefore, we studied myocardial substrate uptake (glucose, lactate, pyruvate, free fatty acids, triglycerides, beta-hydroxybutyrate, and acetoacetate) in 10 7-wk-old lambs with an aortopulmonary left-to-right shunt [61 +/- 3% (SE) of left ventricular output] and 9 control lambs during strenuous treadmill exercise. The hemodynamic reaction to exercise was similar in shunt and control lambs. The peripheral metabolic response to exercise was also similar in the two groups: glucose free fatty acids, and, most prominently, lactate concentrations increased. Myocardial O2 consumption increased but less in shunt than in control lambs because of a smaller increase in heart rate. In both groups myocardial lactate uptake increased substantially at the cost of other substrates, providing the heart with 40% of its oxidative metabolism. Fatty acid uptake was not different between the two groups. In conclusion, our data reveal no essential differences in myocardial substrate uptake between shunt and control lambs during a substantial circulatory load.

Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism

1999 ◽  
Vol 276 (3) ◽  
pp. E427-E434 ◽  
Author(s):  
Labros S. Sidossis ◽  
Bettina Mittendorfer ◽  
David Chinkes ◽  
Eric Walser ◽  
Robert R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Fatty Acid Uptake ◽  
Whole Body ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Similar Extent ◽  
Body Level

The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic, and leg fatty acid metabolism were determined in five volunteers. Catheters were placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids were infused, once in the basal state and, on a different occasion, during infusion of dextrose (clamp; arterial glucose 8.8 ± 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid availability in plasma and fatty acid uptake across the splanchnic region and the leg were similar during the basal and clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreased at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxidation to a similar extent at the whole body level, across the leg, and across the splanchnic region, even when fatty acid availability is constant.

scholarly journals Thyroid Hormone Effects on Whole-Body Energy Homeostasis and Tissue-Specific Fatty Acid Uptake in Vivo

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5639-5648 ◽  
Author(s):  
Lars P. Klieverik ◽  
Claudia P. Coomans ◽  
Erik Endert ◽  
Hans P. Sauerwein ◽  
Louis M. Havekes ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Thyroid Hormone ◽  
Energy Homeostasis ◽  
Fatty Acid Uptake ◽  
Whole Body ◽  
Acid Uptake ◽  
Specific Fatty Acid ◽  
Hormone Effects ◽  
Body Energy

scholarly journals Inhibition of Intestinal Lipid Absorption by Cyanobacterial Strains in Zebrafish Larvae

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 161
Author(s):  
Marta Bellver ◽  
Susana Lemos da Costa ◽  
Begoña Astrain Sanchez ◽  
Vitor Vasconcelos ◽  
Ralph Urbatzka
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Dietary Lipid ◽  
Chain Fatty Acid ◽  
Lipid Absorption ◽  
Whole Body ◽  
Acid Uptake ◽  
Protease Inhibition ◽  
Zebrafish Larvae

Obesity is a complex metabolic disease, which is increasing worldwide. The reduction of dietary lipid intake is considered an interesting pathway to reduce fat absorption and to affect the chronic energy imbalance. In this study, zebrafish larvae were used to analyze effects of cyanobacteria on intestinal lipid absorption in vivo. In total, 263 fractions of a cyanobacterial library were screened for PED6 activity, a fluorescent reporter of intestinal lipases, and 11 fractions reduced PED6 activity > 30%. Toxicity was not observed for those fractions, considering mortality, malformations or digestive physiology (protease inhibition). Intestinal long-chain fatty acid uptake (C16) was reduced, but not short-chain fatty acid uptake (C5). Alteration of lipid classes by high-performance thin-layer chromatography (HPTLC) or lipid processing by fluorescent HPTLC was analyzed, and 2 fractions significantly reduced the whole-body triglyceride level. Bioactivity-guided feature-based molecular networking of LC-MS/MS data identified 14 significant bioactive mass peaks (p < 0.01, correlation > 0.95), which consisted of 3 known putative and 11 unknown compounds. All putatively identified compounds were known to be involved in lipid metabolism and obesity. Summarizing, some cyanobacterial strains repressed intestinal lipid absorption without any signs of toxicity and could be developed in the future as nutraceuticals to combat obesity.

scholarly journals Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue

2009 ◽  
Vol 296 (2) ◽  
pp. E333-E342 ◽  
Author(s):  
Jun Yin ◽  
Zhanguo Gao ◽  
Qing He ◽  
Dequan Zhou ◽  
ZengKui Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Interstitial Oxygen ◽  
Obese Mice ◽  
Cell Type Specificity

Recent studies suggest that adipose tissue hypoxia (ATH) may contribute to endocrine dysfunction in adipose tissue of obese mice. In this study, we examined hypoxia's effects on metabolism in adipocytes. We determined the dynamic relationship of ATH and adiposity in ob/ob mice. The interstitial oxygen pressure (Po2) was monitored in the epididymal fat pads for ATH. During weight gain from 39.5 to 55.5 g, Po2 declined from 34.8 to 20.1 mmHg, which are 40–60% lower than those in the lean mice. Insulin receptor-β (IRβ) and insulin receptor substrate-1 (IRS-1) were decreased in the adipose tissue of obese mice, and the alteration was observed in 3T3-L1 adipocytes after hypoxia (1% oxygen) treatment. Insulin-induced glucose uptake and Akt Ser473 phosphorylation was blocked by hypoxia in the adipocytes. This effect of hypoxia exhibited cell type specificity, as it was not observed in L6 myotubes and βTC6 cells. In response to hypoxia, free fatty acid (FFA) uptake was reduced and lipolysis was increased in 3T3-L1 adipocytes. The molecular mechanism of decreased fatty acid uptake may be related to inhibition of fatty acid transporters (FATP1 and CD36) and transcription factors (PPARγ and C/EBPα) by hypoxia. The hypoxia-induced lipolysis was observed in vivo after femoral arterial clamp. Necrosis and apoptosis were induced by hypoxia in 3T3-L1 adipocytes. These data suggest that ATH may promote FFA release and inhibit glucose uptake in adipocytes by inhibition of the insulin-signaling pathway and induction of cell death.

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