scholarly journals A single amino acid change humanizes long-chain fatty acid binding and activation of mouse peroxisome proliferator-activated receptor α

2014 ◽  
Vol 51 ◽  
pp. 27-36 ◽  
Author(s):  
Dhawal P. Oswal ◽  
Gerald M. Alter ◽  
S. Dean Rider ◽  
Heather A. Hostetler
Keyword(s):  
Fatty Acid ◽  
Amino Acid Change ◽  
Chain Fatty Acid ◽  
Single Amino Acid ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Single Amino Acid Change ◽  
Long Chain

scholarly journals Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice

2012 ◽  
Vol 303 (3) ◽  
pp. G367-G376 ◽  
Author(s):  
Xinping Lu ◽  
Xilin Zhao ◽  
Jianying Feng ◽  
Alice P. Liou ◽  
Shari Anthony ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Gastric Mucosa ◽  
Lipoprotein Lipase ◽  
Chain Fatty Acid ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Long Chain Fatty Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ghrelin Secretion ◽  
Long Chain

Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-γ. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-γ in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion.

scholarly journals Long chain fatty acid binding to human plasma albumin.

1975 ◽  
Vol 250 (6) ◽  
pp. 2333-2338
Author(s):  
JD Ashbrook ◽  
AA Spector ◽  
EC Santos ◽  
JE Fletcher
Keyword(s):  
Fatty Acid ◽  
Human Plasma ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Plasma Albumin ◽  
Fatty Acid Binding ◽  
Long Chain

Hepatic CPT1A Facilitates Liver-Adipose Cross-Talk via Induction of FGF21 in Mice

2021 ◽  
Author(s):  
Wei Sun ◽  
Tao Nie ◽  
Kuai Li ◽  
Wenjie Wu ◽  
Qiaoyun Long ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Metabolic Phenotype ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Long Chain Fatty Acid ◽  
Molecular Events ◽  
Long Chain

<b>Background & Aims</b> <p>Hepatosteatosis, defined as excessive intrahepatic lipid accumulation, represents the first step of NAFLD. When combined with additional cellular stress, this benign status progresses to local and systemic pathological conditions such as NASH and insulin resistance. However, the molecular events directly caused by hepatic lipid build-up, in terms of its impact on liver biology and other peripheral organs, remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is the rate limiting enzyme for long chain fatty acid beta-oxidation in the liver. Here we utilise hepatocyte-specific <i>Cpt1a</i> knockout (LKO) mice to investigate the physiological consequences of abolishing hepatic long chain fatty acid metabolism.</p> <p><b>Approach & Results </b></p> <p>Compared to the wild-type (WT) littermates, high fat diet (HFD)-fed LKO mice displayed more severe hepatosteatosis but were otherwise protected against diet-induced weight gain, insulin resistance, hepatic ER stress, inflammation and damage. Interestingly, increased energy expenditure was observed in LKO mice, accompanied by enhanced adipose tissue browning. RNAseq analysis revealed that the peroxisome proliferator activator alpha (PPARα)- fibroblast growth factor 21 (FGF21) axis was activated in liver of LKO mice. Importantly, antibody-mediated neutralization of FGF21 abolished the healthier metabolic phenotype and adipose browning in LKO mice, indicating that the elevation of FGF21 contributes to the improved liver pathology and adipose browning in HFD-treated LKO mice. </p> <p><b>Conclusions</b></p> Liver with deficient CPT1A expression adopts a healthy steatotic status that protects against HFD-evoked liver damage and potentiates adipose browning in an FGF21-dependent manner. Inhibition of hepatic CPT1A may serve as a viable strategy for the treatment of obesity and NAFLD.

scholarly journals The effect of intracellular pH on long-chain fatty acid uptake in 3T3-L1 adipocytes: evidence that uptake involves the passive diffusion of protonated long-chain fatty acids across the plasma membrane

1996 ◽  
Vol 313 (2) ◽  
pp. 487-494 ◽  
Author(s):  
Bernardo L. TRIGATTI ◽  
Gerhard E. GERBER
Keyword(s):  
Fatty Acids ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acids ◽  
Cytoplasmic Ph ◽  
Long Chain Fatty Acid ◽  
Intact Cells ◽  
Fatty Acid Binding ◽  
Long Chain

To understand the mechanism of long-chain fatty acid permeation of the plasma membrane in mammalian cells, the effects of changes in the cytoplasmic pH on the internalization of physiologically relevant, submicromolar concentrations of uncomplexed long-chain fatty acids were investigated in 3T3-L1 adipocytes. The acidification of the cytoplasm upon NH4Cl prepulsing of intact cells was accompanied by a rapid reduction of cellular long-chain fatty acid uptake (measured as the total accumulation of [9,10-3H]oleate). This was followed by a slow recovery to normal levels of uptake as the cytoplasmic pH recovered. Conventional filtration assays do not distinguish between fatty acid movement across the plasma membrane and intracellular steps, such as binding to cytoplasmic fatty acid-binding proteins or metabolism. While the in vitro binding of a photoreactive fatty acid, 11-m-diazirinophenoxy[11-3H]undecanoate, to a cytoplasmic fatty acid-binding protein was insensitive to changes in pH from pH 7.5 to 5.5, the in vitro conversion of oleate into oleoyl-CoA by cellular acyl-CoA synthetase decreased dramatically. Therefore, the labelling of the 15 kDa cytoplasmic fatty acid-binding protein in intact cells by the photoreactive fatty acid was used as a more direct measure of the permeation of the probe across the plasma membrane. Acidification of the cytoplasm resulted in an immediate reduction in the labelling of this protein in intact adipocytes. Its photolabelling recovered, however, upon the recovery of the cytoplasmic pH to normal levels. This was due to effects of the cytoplasmic pH on the permeation of the photoreactive fatty acid across the plasma membrane rather than its binding to the 15 kDa protein or metabolism in vivo. This is the first demonstration that the movement of physiologically relevant, submicromolar concentrations of uncomplexed long-chain fatty acids across the plasma membrane of intact cells is coupled to the cytoplasmic pH and suggests that it occurs by the diffusion of the protonated long-chain fatty acid through the lipid bilayer.

Long-chain fatty acid-binding to albumin: re-evaluation with directly measured concentrations

1994 ◽  
Vol 1215 (3) ◽  
pp. 321-326 ◽  
Author(s):  
Horst Rose ◽  
Martina Conventz ◽  
Yvan Fischer ◽  
Eberhard Jüngling ◽  
Thomas Hennecke ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Binding ◽  
Long Chain
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