scholarly journals Free Fatty acids receptors (FFAR2 and FFAR3) control cell proliferation by regulating cellular glucose uptake

2019 ◽  
Author(s):  
Mohammad Aziz ◽  
Saeed Al Mahri ◽  
Amal Alghamdi ◽  
Maaged AlAkiel ◽  
Monira Al Aujan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Glucose Uptake ◽  
Microarray Data ◽  
Free Fatty Acid Receptors

Abstract Background Colorectal cancer is a worldwide problem which has been associated with changes in diet and lifestyle pattern. As a result of colonic fermentation of dietary fibres, short chain free fatty acids are generated which activate Free Fatty Acid Receptors 2 and 3 (FFAR2 and FFAR3). FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells. Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis. Methods Transcriptome analysis console was used to analyse microarray data from patients and cell lines. We employed shRNA mediated down regulation of FFAR2 and FFAR3 genes which was assessed using qRT-PCR. Assays for glucose uptake and cAMP generation was done along with immunofluorescence studies. For measuring cell proliferation, we employed real time electrical impedance based assay available from xCelligence. Results Microarray data analysis of colorectal cancer patient samples showed a significant down regulation of FFAR2 gene expression. This prompted us to study the FFAR2 in colorectal cancer. Since, FFAR3 shares significant structural and functional homology with FFAR2, we knocked down both these receptors in colorectal cancer cell line HCT 116. These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of GLUT1. Since, FFAR2 and FFAR3 signal through G protein subunit (Gαi), knockdown of these receptors was associated with increased cAMP. Inhibition of PKA did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway. Conclusion: Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of protein kinase A mediated cAMP signalling. Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes. This study paves the way to understand the mechanism of action of short chain free fatty acid receptors in colorectal cancer.

Abstract 5299: Role of short chain free fatty acid receptors in colorectal cancer

2019 ◽  
Author(s):  
Amal AlGhamdi ◽  
Saeed AlMahri ◽  
Maaged AlAkiel ◽  
Sameer Mohammad ◽  
Mohammad Aziz
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Short Chain ◽  
Free Fatty Acid Receptors

scholarly journals Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man.

1991 ◽  
Vol 87 (1) ◽  
pp. 83-89 ◽  
Author(s):  
L C Groop ◽  
R C Bonadonna ◽  
M Shank ◽  
A S Petrides ◽  
R A DeFronzo
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Lipid Oxidation ◽  
Free Fatty Acids

Abstract 5299: Role of short chain free fatty acid receptors in colorectal cancer

2019 ◽  
Author(s):  
Amal AlGhamdi ◽  
Saeed AlMahri ◽  
Maaged AlAkiel ◽  
Sameer Mohammad ◽  
Mohammad Aziz
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Short Chain ◽  
Free Fatty Acid Receptors

Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 1397-1404
Author(s):  
Adrian Bartoszek ◽  
Jakub Fichna ◽  
Aleksandra Tarasiuk ◽  
Agata Binienda ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Current Knowledge ◽  
Developed Countries ◽  
Future Directions ◽  
Screening Programs ◽  
Pharmacological Targets ◽  
The Family ◽  
Free Fatty Acid Receptors

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

Effect of insulin on free fatty acid uptake by hepatocytes in the duck

1984 ◽  
Vol 102 (3) ◽  
pp. 381-386 ◽  
Author(s):  
R. Gross ◽  
P. Mialhe
Keyword(s):  
Fatty Acids ◽  
Growth Hormone ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Metabolism ◽  
Free Fatty Acids ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Low Doses ◽  
Higher Doses

ABSTRACT To elucidate the hypolipacidaemic effect of insulin in ducks, its action on the uptake of free fatty acids (FFA) by duck hepatocytes was determined. At low doses (10 mu./l) insulin stimulated FFA uptake. This effect was not observed with higher doses of insulin (20, 30 and 50 mu./l). Growth hormone at physiological concentrations and corticosterone (14·4 nmol/l) decreased basal activity, probably by reducing glucose metabolism and consequently α-glycerophosphate (α-GP) supply. Insulin was able to reverse the inhibition induced by GH and corticosterone on both FFA uptake and α-GP production. These results therefore suggest that the hypolipacidaemic effect of insulin may be partly mediated by its action on hepatic FFA uptake. J. Endocr. (1984) 102, 381–386

Epinephrine-insulin antagonism on free fatty acid release

1961 ◽  
Vol 201 (5) ◽  
pp. 815-818 ◽  
Author(s):  
John J. Spitzer ◽  
William T. McElroy
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Blood Sugar ◽  
Drug Administration ◽  
Hepatic Uptake ◽  
Fatty Acid Release ◽  
Plasma Ffa ◽  
Acid Release

The effects of epinephrine or norepinephrine were studied in dogs receiving insulin plus glucose prior to and during administration of the amine. Epinephrine caused a significantly smaller elevation of free fatty acids (FFA) with than without insulin plus glucose administration. Blood sugar responses were quantitatively similar. Epinephrine increased both hepatic uptake of FFA and hepatic release of glucose; these changes were similar to the ones found previously in dogs not receiving insulin plus glucose. The action of norepinephrine on elevating plasma FFA was only slightly and not significantly affected by the administration of insulin plus glucose. When the order of drug administration was reversed, infusion of insulin plus glucose lowered plasma FFA levels and hepatic FFA uptake in animals already receiving either epinephrine or nonepinephrine.

Changes in plasma free fatty acid concentrations on passage through the dog kidney

1961 ◽  
Vol 200 (5) ◽  
pp. 1095-1098 ◽  
Author(s):  
Frank J. Hohenleitner ◽  
John J. Spitzer
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Renal Plasma Flow ◽  
Plasma Free Fatty Acid ◽  
Systemic Artery ◽  
Arterial Concentration ◽  
Dog Kidney ◽  
Anesthetized Dogs

To measure the renal removal of free fatty acids from the plasma, simultaneous determinations of this metabolite were performed in a systemic artery and a renal vein in the anesthetized dogs. Renal plasma flow was also determined by the PAH method, and the renal uptake of free fatty acids was calculated. Concentrations of free fatty acids in renal venous plasma were usually lower than the arterial concentrations. The arteriovenous differences were statistically highly significant. The results also suggested that the degree of free fatty acid removal was proportional to the arterial concentration of this metabolite.

Free fatty acid concentration and composition in arterial blood

1962 ◽  
Vol 203 (2) ◽  
pp. 306-310 ◽  
Author(s):  
Martin E. Rothlin ◽  
Christine B. Rothlin ◽  
Vernon E. Wendt
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Free Fatty Acid Concentration ◽  
Arterial Blood ◽  
Arterial Concentration ◽  
The Subject ◽  
Palmitic Acids

The effect of the administration of norepinephrine, glucose and insulin, pentobarbital, and Hypertensin on the arterial concentration and composition of plasma free fatty acids (FFA) has been studied in man and dog. With a rise of the FFA concentration as produced by norepinephrine, the contribution of oleic acid to the total FFA increased, while that of stearic and palmitic acids decreased. The reverse changes in the FFA composition were observed when their arterial level fell under the influence of other agents studied. The FFA composition was dependent on the FFA concentration in arterial blood, but not on the experimental condition of the subject or animal at the time of analysis. At high FFA levels, the FFA composition approached that of depot fat.

Reaction of Free Fatty Acids with Protein in Cod Muscle Frozen and Stored at −29 C after Aging in Ice

1969 ◽  
Vol 26 (10) ◽  
pp. 2727-2736 ◽  
Author(s):  
Margaret L. Anderson ◽  
Elinor M. Ravesi
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Complex Formation ◽  
Free Fatty Acids ◽  
Phase Contrast ◽  
Reaction Rate ◽  
Frozen Storage ◽  
Phase Contrast Micrographs ◽  
Protein Extractability

Freezing and holding cod muscle in the frozen state favored the association process that involves protein–free fatty acid (FFA) complex formation and begins during aging in ice. Changes in protein extractability, in ultracentrifugal patterns of protein extracted, and in phase contrast micrographs of inextractable muscle fragments were followed in muscle that had been aged in ice to produce various contents of FFA and then frozen and held at −29 C. After 11 months, these changes, which took place largely during the first week of storage, were comparable with those that occur when the FFA are formed during frozen storage. The results were consistent with a reaction rate that was greater at −29 C than at temperatures a few degrees above 0 C.

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