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 ◽  
...  

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.

1999 ◽  
Vol 276 (3) ◽  
pp. E427-E434 ◽  
Author(s):  
Labros S. Sidossis ◽  
Bettina Mittendorfer ◽  
David Chinkes ◽  
Eric Walser ◽  
Robert R. Wolfe

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.


Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5639-5648 ◽  
Author(s):  
Lars P. Klieverik ◽  
Claudia P. Coomans ◽  
Erik Endert ◽  
Hans P. Sauerwein ◽  
Louis M. Havekes ◽  
...  

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 161
Author(s):  
Marta Bellver ◽  
Susana Lemos da Costa ◽  
Begoña Astrain Sanchez ◽  
Vitor Vasconcelos ◽  
Ralph Urbatzka

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.


2017 ◽  
Vol 122 (5) ◽  
pp. 1188-1197 ◽  
Author(s):  
Kumail K. Motiani ◽  
Anna M. Savolainen ◽  
Jari-Joonas Eskelinen ◽  
Jussi Toivanen ◽  
Tamiko Ishizu ◽  
...  

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.


2015 ◽  
Vol 118 (9) ◽  
pp. 1172-1180 ◽  
Author(s):  
Jari-Joonas Eskelinen ◽  
Ilkka Heinonen ◽  
Eliisa Löyttyniemi ◽  
Virva Saunavaara ◽  
Anna Kirjavainen ◽  
...  

We tested the hypothesis that sprint interval training (SIT) causes larger improvements in glucose and free fatty acid uptake (FFAU) in lower and upper body muscles than moderate-intensity training (MIT). Twenty-eight healthy, untrained, middle-aged men were randomized into SIT ( n = 14, 4–6 × 30 s of all-out cycling/4 min recovery) and MIT groups [ n = 14, 40–60 min cycling at 60% of peak O2 uptake (V̇o2 peak)] and completed six training sessions within 2 wk. Pre- and postmeasurements included V̇o2 peak, whole body (M-value), muscle-specific insulin-stimulated glucose uptake (GU), and fasting FFAU measured with positron emission tomography in thigh [quadriceps femoris (QF) and hamstrings] and upper body (deltoids, biceps, and triceps brachii) muscles. V̇o2 peak and M-value improved significantly by 6 and 12% in SIT, and 3 and 8% in MIT, respectively,. GU increased significantly only in the QF, and there was no statistically significant difference between the training modes. GU increased in all four heads of QF in response to SIT, but only in the vasti muscles in response to MIT, whereas in rectus femoris the response was completely lacking. Training response in FFAU in QF was smaller and nonsignificant, but it also differed between the training modes in the rectus femoris. In conclusion, SIT and MIT increased insulin-stimulated GU only in the main working muscle QF and not in the upper body muscles. In addition, the biarticular rectus femoris did not respond to moderate-intensity training, reflecting most probably poor activation of it during moderate-intensity cycling.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1866-P
Author(s):  
RUN ZHOU YE ◽  
SERGE PHOENIX ◽  
CHRISTOPHE NOLL ◽  
EMILIE MONTASTIER ◽  
FRÉDÉRIQUE FRISCH ◽  
...  

1990 ◽  
Vol 79 (2) ◽  
pp. 167-174 ◽  
Author(s):  
M. Walker ◽  
G. R. Fulcher ◽  
C. Catalano ◽  
G. Petranyi ◽  
H. Orskov ◽  
...  

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.


2008 ◽  
Vol 104 (5) ◽  
pp. 769-775 ◽  
Author(s):  
Koji Kitada ◽  
Kazuo Kubota ◽  
Ryoichi Nagatomi ◽  
Masatoshi Itoh ◽  
Manabu Tashiro ◽  
...  

1997 ◽  
Vol 273 (5) ◽  
pp. H2473-H2480 ◽  
Author(s):  
Maija T. Mäki ◽  
Merja T. Haaparanta ◽  
Matti S. Luotolahti ◽  
Pirjo Nuutila ◽  
Liisa-Maria Voipio-Pulkki ◽  
...  

Glucose uptake appears preserved or even enhanced in the chronically dysfunctional but viable myocardium. However, the use of other fuels such as free fatty acids (FFA) remains unknown. We studied FFA uptake in the chronically dysfunctional but viable myocardium in seven patients with an occluded major coronary artery and a corresponding chronic wall motion abnormality but no previous infarction. Myocardial FFA uptake kinetics in the fasting state were measured with positron emission tomography (PET) and 14( R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). The FFA uptake index was calculated by multiplying the fractional [18F]FTHA uptake with serum FFA concentration. Myocardial blood flow (MBF) was measured with [15O]H2O and PET. Myocardial viability was confirmed with a static18F-labeled 2-fluoro-2-deoxy-d-glucose PET imaging and a follow-up echocardiography in the revascularized patients. Regional MBF was slightly but not significantly lower in the dysfunctional compared with normal myocardial segments (0.76 ± 0.18 vs. 0.81 ± 0.14 ml ⋅ min−1 ⋅ g−1, means ± SD; P = 0.16). The fractional [18F]FTHA uptake rates [0.11 ± 0.03 vs. 0.11 ± 0.04 ml ⋅ g−1 ⋅ min−1; not significant (NS)], and the FFA uptake indexes (5.8 ± 1.7 vs. 5.8 ± 2.1 μmol ⋅ 100 g−1 ⋅ min−1; NS) were similar in the dysfunctional but viable and in the normal myocardial regions. Thus, in the chronically dysfunctional but viable (collateral-dependent) myocardium, the fatty acid uptake probed by [18F]FTHA appears preserved. Taken together with preserved glucose uptake, the results indicate that there is uncoupling of substrate uptake and mechanical function in the chronically dysfunctional but viable myocardium.


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