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

Long-chain fatty acids are both important metabolites as well as signaling molecules. Fatty acid transport proteins are key mediators of cellular fatty acid uptake and recent transgenic and knockout animal models have provided new insights into their contribution to energy homeostasis and to pathological processes, including obesity and insulin desensitization.

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Inhibition of Intestinal Lipid Absorption by Cyanobacterial Strains in Zebrafish Larvae

Marine Drugs ◽

10.3390/md19030161 ◽

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.

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Sex differences in hepatic fatty acid uptake reflect a greater affinity of the transport system in females

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.263.3.g380 ◽

1992 ◽

Vol 263 (3) ◽

pp. G380-G385 ◽

Cited By ~ 2

Author(s):

D. Sorrentino ◽

S. L. Zhou ◽

E. Kokkotou ◽

P. D. Berk

Keyword(s):

Plasma Membrane ◽

Fatty Acid ◽

Transport System ◽

Fatty Acid Uptake ◽

Surface Expression ◽

Female Rats ◽

Acid Uptake ◽

Fatty Acid Binding ◽

Male And Female Rats

In this study, we examined the hypothesis that the reported sex difference in hepatic free fatty acid (FFA) uptake involves the putative FFA transport system, the plasma membrane fatty acid binding protein (FABPpm). In hepatocytes isolated from both male and female rats, initial [3H]oleate uptake velocity reflected transmembrane influx and not subsequent metabolism and was a saturable function of the unbound oleate concentration. Although Vmax values were similar (61 +/- 2 vs. 65 +/- 5 pmol.min-1.5 x 10(4) cells-1 for females and males, respectively), the apparent Km was significantly smaller in females (40 +/- 4 vs. 90 +/- 11 nM; P less than 0.05), reflecting faster influx velocities in female cells over a range of unbound oleate concentrations. The oleate efflux rate constant was also greater in females (0.280 +/- 0.014 vs. 0.198 +/- 0.020 min-1; P less than 0.05) despite their greater hepatic content of cytosolic FABP. Finally, despite the greater rates of transmembrane FFA flux in female hepatocytes, the surface expression of FABPpm was virtually identical in the two sexes (2.5 +/- 0.5 vs. 2.4 +/- 0.4 microgram/10(6) cells). Collectively, these data indicate that at FFA-to-albumin ratios occurring in vivo the plasma membrane of female hepatocytes transports oleate bidirectionally at a greater rate than that of male hepatocytes. A sex-related difference in the functional affinity of FABPpm for FFA appears the most likely explanation for the greater oleate uptake in females.

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Retinoic Acid Receptor β Stimulates Hepatic Induction of Fibroblast Growth Factor 21 to Promote Fatty Acid Oxidation and Control Whole-body Energy Homeostasis in Mice

Journal of Biological Chemistry ◽

10.1074/jbc.m112.429852 ◽

2013 ◽

Vol 288 (15) ◽

pp. 10490-10504 ◽

Cited By ~ 55

Author(s):

Yu Li ◽

Kimberly Wong ◽

Kenneth Walsh ◽

Bin Gao ◽

Mengwei Zang

Keyword(s):

Retinoic Acid ◽

Fatty Acid ◽

Energy Homeostasis ◽

Retinoic Acid Receptor ◽

Whole Body ◽

Fibroblast Growth Factor 21 ◽

Acid Oxidation ◽

Fibroblast Growth ◽

And Control ◽

Body Energy

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00579.2010 ◽

2011 ◽

Vol 300 (3) ◽

pp. E445-E453 ◽

Cited By ~ 56

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.

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A System for In Vivo Imaging of Hepatic Free Fatty Acid Uptake

Gastroenterology ◽

10.1053/j.gastro.2016.10.002 ◽

2017 ◽

Vol 152 (1) ◽

pp. 78-81.e2 ◽

Cited By ~ 5

Author(s):

Hyo Min Park ◽

Kim A. Russo ◽

Grigory Karateev ◽

Michael Park ◽

Elena Dubikovskaya ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

In Vivo Imaging ◽

Fatty Acid Uptake ◽

Acid Uptake

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Direct Free Fatty Acid Uptake Into Human Adipocytes In Vivo: Relation to Body Fat Distribution

Diabetes ◽

10.2337/db06-1680 ◽

2007 ◽

Vol 56 (5) ◽

pp. 1369-1375 ◽

Cited By ~ 93

Author(s):

S. Shadid ◽

C. Koutsari ◽

M. D. Jensen

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Body Fat ◽

Fat Distribution ◽

Fatty Acid Uptake ◽

Body Fat Distribution ◽

Acid Uptake ◽

Human Adipocytes

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Theobromine ameliorates nonalcoholic fatty liver disease by regulating hepatic lipid metabolism via mTOR signaling pathway in vivo and in vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0259 ◽

2020 ◽

Author(s):

Dan Wei ◽

Shaofei Wu ◽

Jie Liu ◽

Xiaoqian Zhang ◽

Xiaoling Guan ◽

...

Keyword(s):

Fatty Acid ◽

Signaling Pathway ◽

Fatty Acid Oxidation ◽

Fatty Acid Uptake ◽

Mtor Signaling ◽

Acid Oxidation ◽

Acid Uptake ◽

Mtor Signaling Pathway

Theobromine, a methylxanthine present in cocoa, has been shown to possess many beneficial pharmacological properties such as anti-oxidative stress, anti-inflammatory property, and anti-microbial activity. In this study, we investigated the effects of theobromine on NAFLD and the possible underlying mechanisms in vivo and in vitro. The results showed that theobromine reduced body weight, fat mass and improved dyslipidemia. Theobromine decreased liver weight, mitigated liver injury, and significantly reduced hepatic TG level in mice with obesity. Histological examinations also showed hepatic steatosis was alleviated after theobromine treatment. Furthermore, theobromine reversed the elevated mRNA and protein expression of SREBP-1c, FASN, CD36, FABP4 and the suppressed expression of PPARα, CPT1a in the liver of mice with obesity, which were responsible for lipogenesis, fatty acid uptake and fatty acid oxidation respectively. In vitro, theobromine also downregulated SREBP-1c, FASN, CD36, FABP4 and upregulated PPARα, CPT1a mRNA and protein levels in hepatocytes in a dose-dependent manner, while these changes were reversed by L-Leucine, an mTOR agonist. The present study demonstrated that theobromine improved NAFLD by inhibiting lipogenesis, fatty acid uptake and promoting fatty acid oxidation in the liver and hepatocytes, which might be associated with its suppression of mTOR signaling pathway.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.276.3.e427 ◽

1999 ◽

Vol 276 (3) ◽

pp. E427-E434 ◽

Cited By ~ 10

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.

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