The long chain fatty acid oleate activates mouse intestinal afferent nerves in vitro

2013 ◽  
Vol 91 (5) ◽  
pp. 375-379 ◽  
Author(s):  
W. Andrew Webster ◽  
Michael J. Beyak
Keyword(s):  
Fatty Acid ◽  
Gastrointestinal Tract ◽  
Chain Fatty Acid ◽  
Nutrient Sensing ◽  
Enteroendocrine Cells ◽  
Vagal Afferents ◽  
In Vivo Studies ◽  
Long Chain Fatty Acid ◽  
Long Chain

Vagal afferents innervating the gastrointestinal tract serve an important nutrient-sensing function, and these signals contribute to satiety. Detection of nutrients occurs largely through the release of mediators from specialized enteroendocrine cells within the mucosa of the gastrointestinal tract. The signaling pathways leading to vagal afferent activation are not clear; however, previous in-vivo studies have implicated a role for cholecystokinin (CCK). We used an in vitro intestinal afferent extracellular recording preparation to study the effect of luminal perfusion of the long chain fatty acid oleate on mouse intestinal afferent activity. Oleate activated intestinal afferents in a concentration-dependent fashion, with an EC50 value of approximately 25 mmol/L. The L-type calcium channel blocker nicardipine attenuated the effect of oleate. Vagotomy resulted in a significant (>60%) reduction of the responses to both oleate and CCK. The CCK-1 receptor antagonist lorglumide nearly abolished responses to CCK and oleate. Our experiments therefore suggest that oleate activates intestinal afferents, with vagal afferents primarily involved; however, nonvagal fibres also contribute. The activation is dependent on CCK release, likely via activation of L-type channels on mucosal enteroendocrine cells, finally resulting in activation of CCK-1 receptors on the afferent terminals.

Myocardial carnitine palmitoyltransferase I expression and long-chain fatty acid oxidation in fetal and newborn lambs

2004 ◽  
Vol 286 (6) ◽  
pp. H2243-H2248 ◽  
Author(s):  
Beatrijs Bartelds ◽  
Janny Takens ◽  
Gioia B. Smid ◽  
Victor A. Zammit ◽  
Carina Prip-Buus ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Left Ventricular ◽  
Chain Fatty Acid ◽  
Carnitine Palmitoyltransferase ◽  
Long Chain Fatty Acid ◽  
Carnitine Palmitoyltransferase I ◽  
Cpt I ◽  
Long Chain

Carnitine palmitoyltransferase I (CPT I) catalyzes the conversion of acyl-CoA to acylcarnitine at the outer mitochondrial membrane and is a key enzyme in the control of long-chain fatty acid (LC-FA) oxidation. Because myocardial LC-FA oxidation increases dramatically after birth, we determined the extent to which CPT I expression contributes to these changes in the perinatal lamb. We measured the steady-state level of transcripts of the CPT1A and CPT1B genes, which encode the liver (L-CPT I) and muscle CPT I (M-CPT I) isoforms, respectively, as well as the amount of these proteins, their total activity, and the amount of carnitine in left ventricular tissue from fetal and newborn lambs. We compared these data with previously obtained myocardial FA oxidation rates in vivo in the same model. The results showed that CPT1B was already expressed before birth and that total CPT I expression transiently increased after birth. The protein level of M-CPT I was high throughout development, whereas that of L-CPT I was only transiently upregulated in the first week after birth. The total CPT I activity in vitro also increased after birth. However, the increase in myocardial FA oxidation measured in vivo (112-fold) by far exceeded the increase in gene expression (2.2-fold), protein amount (1.1-fold), and enzyme activity (1.2-fold) in vitro. In conclusion, these results stress the importance of substrate supply per se in the postnatal increase in myocardial FA oxidation. M-CPT I is expressed throughout perinatal development, making it a primary target for metabolic modulation of myocardial FA oxidation.

scholarly journals In Vivo Optical Metabolic Imaging of Long-Chain Fatty Acid Uptake in Orthotopic Models of Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 148
Author(s):  
Megan C. Madonna ◽  
Joy E. Duer ◽  
Joyce V. Lee ◽  
Jeremy Williams ◽  
Baris Avsaroglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Triple Negative ◽  
Fatty Acid Uptake ◽  
Chain Fatty Acid ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
Long Chain

Targeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo and demonstrate its relevance to study both tumor metabolic reprogramming directly, as well as the effectiveness of drugs targeting lipid metabolism. Specifically, we developed a quantitative optical approach to spatially and longitudinally map the kinetics of long-chain fatty acid uptake in in vivo murine models of breast cancer using a fluorescently labeled palmitate molecule, Bodipy FL c16. We chose intra-vital microscopy of mammary tumor windows to validate our approach in two orthotopic breast cancer models: a MYC-overexpressing, transgenic, triple-negative breast cancer (TNBC) model and a murine model of the 4T1 family. Following injection, Bodipy FL c16 fluorescence increased and reached its maximum after approximately 30 min, with the signal remaining stable during the 30–80 min post-injection period. We used the fluorescence at 60 min (Bodipy60), the mid-point in the plateau region, as a summary parameter to quantify Bodipy FL c16 fluorescence in subsequent experiments. Using our imaging platform, we observed a two- to four-fold decrease in fatty acid uptake in response to the downregulation of the MYC oncogene, consistent with findings from in vitro metabolic assays. In contrast, our imaging studies report an increase in fatty acid uptake with tumor aggressiveness (6NR, 4T07, and 4T1), and uptake was significantly decreased after treatment with a fatty acid transport inhibitor, perphenazine, in both normal mammary pads and in the most aggressive 4T1 tumor model. Our approach fills an important gap between in vitro assays providing rich metabolic information at static time points and imaging approaches visualizing metabolism in whole organs at a reduced resolution.

Effects of certain long-chain fatty acid combinations on the ruminal microbe species relating to fermentation type in vitro

2018 ◽  
Author(s):  
Y. J. Jing ◽  
Y. F. Wang ◽  
J. Gao ◽  
J. L. Ouyang ◽  
L. Cheng
Keyword(s):  
Fatty Acid ◽  
Culture Medium ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Butyrivibrio Fibrisolvens ◽  
Acid Type ◽  
Group A ◽  
Group B ◽  
Long Chain

This experiment was conducted to investigate the effects of certain long-chain fatty acid combinations on ruminal microbial community in vitro. Three cows fitted with permanent ruminal cannulas were used to provide rumen liquor for the in vitro trail. The treatments were fatty acid combinations of stearic acid, oleic acid, linoleic acid and linolenic acid, which respectively were group A (calcium palmitate, control), B (1.5%, 1.0%, 0.5% and 1.5%, acetic type fermentation), C (1.5%, 1.0%, 1.5% and 1.0%, propionic acid type fermentation), D (1.0%, 1.5%, 1.5% and 0.5%, butyric acid type fermentation). Three goats fitted with rumen cannula were used to provide the culture medium was collected for the measurement of the rumen microorganism in vitro culture. Culture medium was collected at 0, 3, 6, 12, 18 and 24 h. The results demonstrated that, except for Ruminococcus albus, all the other bacterial genus had significant differences between groups (P less than 0.05). The Fibrobacter succinogenes and Ruminococcusflavefaciens, Clostridium proteoclasticum and Ruminobacter amylophilus were higher in group B; Butyrivibrio fibrisolvens, Megasphaera elsdenii and Ruminococcus bromii were higher in group C; while Pseudobutyrivibrio ruminis was higher in group D. Different higher species in different treatments described above related to their fermentation type. It was also observed that, bacteria were the dominant flora in rumen and Megasphaera elsdeniiwere the dominant species in bacterial fraction no matter what the treatment is. It was therefore concluded that, certain fatty acid combinations have remarkable effects on the amount of ruminal specific bacteria species,mainly related to their fermentation type.

In Vitro Regulation of Enzymes of the Renin-angiotensin-aldosterone System by Isoquercitrin, Phloridzin and their Long Chain Fatty Acid Derivatives

2014 ◽  
Vol 4 (5) ◽  
pp. 208 ◽  
Author(s):  
Khushwant S Bhullar ◽  
Ziaullah Ziaullah ◽  
Vasantha Rupasinghe
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Eicosapentaenoic Acid ◽  
Acid Ester ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Renin Angiotensin Aldosterone System ◽  
Fatty Acid Derivatives ◽  
Long Chain

Background: Hypertension is a crucial risk factor for development of cardiovascular and neurological diseases. Flavonoids exhibit a wide range of biological effects and have had increased interest as a dietary approach for the prevention or possible treatment of hypertension. However, continuous efforts have been made to structurally modify natural flavonoids with the hope of improving their biological activities. One of the methods used for the possible enhancement of flavonoid efficacy is enzymatic esterification of flavonoids with fatty acids. Objective: The current study is designed to investigate the antihypertensive activity of isoquercitrin (quercetin-3-O-glucoside, Q3G) and phloridzin (PZ) in comparison to their twelve long chain fatty acid derivatives via enzymatic inhibition of renin angiotensin aldosterone system (RAAS) enzymes.Methods: The novel flavonoid esters were synthesized by the acylation of isoquercitrin and phloridzin with long chain unsaturated and saturated fatty acids (C18–C22). These acylated products were then tested for their in vitro angiotensin converting enzyme (ACE), renin and aldosterone synthase activities.Results: The linoleic and α-linolenic acid esters of PZ were the strongest (IC50 69.9-70.9 µM) while Q3G and PZ (IC50 >200 µM) were the weakest renin inhibitors in vitro (p≤0.05). The eicosapentaenoic acid ester of PZ (IC50 16.0 µM) was the strongest inhibitor of ACE, while PZ (IC50 124.0 µM) was the weakest inhibitor (p≤0.05) among all tested compounds. However, all investigated compounds had low (5.0-11.9%) or no effect on aldosterone synthase inhibition (p≤0.05). The parent compound Q3G and the eicosapentaenoic acid ester of PZ emerged as the strongest ACE inhibitors.Conclusions: The structural modification of Q3G and PZ significantly improved their antihypertensive activities. The potential use of PZ derivatives as natural health products to treat hypertension needs to be further evaluated.Keywords: hypertension, phloridzin, isoquercitrin, flavonoids, ACE, renin, RAAS, acylation, fatty acids 

Sign in / Sign up

Export Citation Format

Share Document